Complete List of Terms and Definitions for Molecular Basis of Disease, Block 5

Terms Definitions
456. What type of hyperammonemia is genetic and most severe? 456. Type I
220. In summary, what does ether glycerolipid synthesis require (list of items)? 220. NADPH,AylCoA, DHAP, activate ethanolamine
533. What is involved in synthesis of serotonin and melatonin (AA)? 533. Trp
73. What is the logic of CPT1/2? 73. FA’s are carried via O-acyl carnitine linkages which have an eq. constant near 1, due to orbital overlap bw C and O , usually this is not the case however it takes the place of the high energy due to thioeser bonds that have less overlap beteen S and C therefore less resonance stabilization and less energy than usual
198. What is the action of pancreatic lipase? 198. Hydrolyze TAG to DAG and 2MG
591. Where does ¾ of heme come from? 591. Hemoglobin
615. What is jaundice with unconjugated hyperbilirubinemia caused by? 615. Deficiency in UDP-GA transferase (gilberts syndrome), crigler najjar syndrome, hepatitis, etc.
595. What is bilirubin carried to the liver on? 595. Albumin
535. What is the function of melatonin? 535. Darkness hormone (circadian cycle), released from pineal gland
12. What enzyme cleaves cholesterol esters? 12. Cholesterol lipase
455. What is the alanine cycle? 455. Glu in muscle transaminated to Ala which is transferred to liver and converted to pyruvate for further metabolism
464. What converts urea to carbonic acid and ammonia? 464. Urease generated by bacterium proteus mirabilis
370. What is the basis of this disease? 370. Increased PRPP which activates purine synthesis
562. What is ALA synthase stimulated by? 562. Requirements for p450’s which include barbiturates and steroids
167. Do eicosanoids have a long lifetime? 167. No
164. T or F: Eicosanoids derive from omega 6 and omega 3 FA’s 164. T
185. What pathway forms HETES, leukotrienes, lipoxins? 185. Lipoxygenase pathway
442. How is urea in plasma measured? 442. Blood urea nitrogen (BUN), typically 8-20mg/dl
343. What is the precursor of AMP and GMP? 343. IMP
118. What enzyme provides cytosolic NADPH for FA synthesis? There are two possible answers to this question. 118. Malic enzyme (reduces malate), or PPP via G6P DH (oxidative portion)
23. What transfers proteins to ApoB particles? 23. Micosomal TG transfer protein (MTP)
87. What step is diff. in peroxisomal oxidation of FA? How many times is oxidation repeated? 87. 1st step, until chain is 6-10C’s ong and can be transported to mt. where oxidation is completed
447. What is the 3rd step in the urea cycle? 447. Arginnosuccinate synthetase to form Argininosuccinate from asprate and citrulline
355. What is the rate limiting step in GMP synthesis? 355. IMPDH
287. Where is testsosterone produced? Estrogen? 287. Leydig cells, ovarian granulose cells
20. Are cholesterols present in chylomicrons? 20. Yes (hydroxyl groups pointed out)
146. Describe three types of local hormones produced by eicosanoids 146. Prostaglandin (PG), thromoxanes(TX), Leukotrienes (LT)
462. What are some characteristics of OTC deficiency? 462. Increased carbomoyl phosphate, increased orotic acid (via CPSII in purine synthesis)
641. What mobilizes fuels during acute stress? 641. Epi
449. What is the 5th step? 449. Arginase to cleave urea off argininosuccinate and produce ornithine (cycle is complete)
53. How many high energy phosphate bonds are required just for activation of FA to FA-CoA? 53. 2
488. What could cause a deficiency in cystathionase? 488. Dietary deficiency of pyridoxine(Vit. B6) or Vit. B12
609. What type of BR can cause neurological problems (kernicterus)? 609. Conjugated
406. What is an inhibitor of reverse transcriptase? 406. AZT
316. What does LDL receptor bind to? 316. ApB-100, ApoE and LDL
155. What are the two activities of prostaglandin synthase? 155. Cyclooxygenase, peroxidase
526. What chromosome is ocular albinism associated with? 526. X, effects mostly eye movements
435. What are Asn and Gln deaminated by and what do they form from these deaminations? 435. Asp, Glu via asparaginase and glutaminase
197. What are fxn. Of TAG? 197. Transport and store FA
48. What can lack of insulin in Type 1 diabetes lead to ( in terms of FA metabolism)? 48. Ketoacidosis
357. In making GMP is ATP or GTP used in GMP synthetase? 357. ATP (to keep the balance of ATP/GTP similar in vivo)
596. T or F: bilirubin is an anion 596. T
340. What are the purines? Pyrimidines? 340. Purines: AG, Pyrmidines: TC
292. What is the major inducer of 1-alpha hydroxylase 292. PTH which is induced by low calcium
14. Through what circulation are bile salts returned to the liver? 14. enterohepatic circulation
383. Are pyrimidines synthesized on a ribose ring like purines ? 383. No, they are synthesized then attached later
245. What is most of cholesterol esterfied to in the circulation? 245. Fatty acids
642. What provides for changing requirements over long term (hormone)? 642. Cortisol
420. What are symptoms of hartnups disease? 420. Dermatitis, diarrhea, dementia
336. What is the defect in familial hypercholesterolemia? Familial combined hyperlipidemia? Familial dysbetalipoproteinemia? 336. LDL receptor, overproduction ApoB100, E2/E2 isoform defective remnant binding to LDL receptor
568. What does absence of cosynthase result in? 568. Formation of porphyrin rings with no functions (uroporphyrinogen I) which accumulate in urine (congenital erythropoietic porphyria)
221. Give some examples of sphingolipids 221. Sphingomyelin, cerebrosides, sulfatides, globosides, gangliosides
433. What is an enzyme that uses NADPH to produce ammonia for the urea cycle? 433. Glutamate DH
22. If the B –apoprotein gene is going to produce a protein destined for the intestine how much of the AA transcript is transcribed? 22. 48%, thus ApoB-48
119. What else can citrate provide for FA synthesis? 119. AcetylCoA via citrate lyase (OAA becomes malate via malate DH)
564. What metal can inhibit ALA dehydratase? 564. Lead
297. What kind of lipoproteins are present in the intestine? 297. CM, small amounts of vldl, hdl
490. What is the treatment for homocystinuria? 490. Low met diet, high doses of pyridoxine
232. What are ceramide-gal called? Ceramide-glc? Ceramide-glc-gal? 232. Galactocerebrosies, glucocerebrosides, lactosyl-ceramide
67. What is similarity between CAC and β-oxidation? 67. Hydration, and oxidation of metabolites to produce FADH2 and NADH
40. What are some examples of monounsaturated FA? 40. palmitoleate, oleate (18C)
482. What intermediate is used in Met degradation for methyl transfer? 482. SAM
633. What are the two key fuels in the fasting state? 633. B-hydroxybutyrate, acetoacetate (note dr. nishimoto’s last exam question is contrary to this)
253. What puts cholesterols in chylomicrons? 253. MTP
288. Does testosterone increase muscle mass? 288. Yes
348. What is the commited step in purine synthesis? 348. GPAT
493. T or F: Any defective step in Phe or Tyr synthesis causes severe diseases 493. T
529. What is norepi converted to in presence of SAM? 529. Epi
480. In cysteine metabolism where does the sulfur originally come from? 480. Met
394. What AA’s are involved in electron transfer in RR? 394. Tyrosine, Cysteine
238. Where does degradation of sphingolipids occur? 238. Lysosome
131. What is the 3rd step? 131. Reduction of b-ketoacyl group using NADPH
280. What are the two primary bile acids listed in class? 280. Taurocholic acid, taurchenodeoxycholic acid
365. How is AMP converted to IMP? 365. AMP deaminase
211. Is the conversion of phosphatidylserine to phosphatidylethanolamine reversible? 211. Yes
511. What converts guanidoacetate to creatinine? 511. SAM
243. T or F: cholesterol plays a role in artherosclerosis/gallstones. 243. T
414. Presence of what AA’s make protein unstable at N terminus? 414. FLDKR
157. What is the major branch point in Eicosanoid synthesis? 157. PGH2
345. What is the first step in the purine de novo pathway? 345. Production of PRPP from ribose 5 phosphate using PRPS1/PRPS2 (requires ATP)
264. What is the rate limiting step of cholesterol synthesis? 264. HMG CoA reductase
103. How is acetoacetate formed from HMG CoA? 103. HMG CoA lyase
484. What can cysteine be degraded to? 484. Sulfinic acid, in presence of alpha ketoglutarate it can be degraded to pyruvate (thus it is a glucogenic AA)
430. What does Ala + alphaketoglutarate produce via ALT ? 430. Pyruvate and glutamate
187. Where are leukotrienes synthesized? 187. Leukocytes
468. What is the only tissue that has all the pathways for amino acid synthesis and degradation? 468. Liver
300. What are surface peptides of lipoprotein particles with lipid binding properties? 300. Apolipoproteins
68. Where is AcylCoA synthetase located? 68. Bound to outer mt. membrane
159. What drug inhibits PG synthesis? 159. Aspirin via cyclooxygenase enzyme (COX)
313. What is the function of ABCA1/ABCG1? 313. Mediate phospholipid/cholesterol efflux from cells to lipid poor Apo A1 in reverse cholesterol transport
7. What is a 18C monounsaturated FA? 7. Oleate
579. Would complete deficiency of a heme biosynthetic enzyme ever happen? 579. No, it would result in death
534. What is the function of serotonin? 534. Regulate anger, body temp, mood, sleep, vomiting, sexuality, appetite
136. Beginning with Acetyl CoA and malonyl CoA what is the reaction to form palmitate? 136. AcetylCoA+7 malonyl CoA+14NADPHàpalmitate +7CO2+7NADP+8CoA
327. Is transfer of CM from golgi to BLM microtubule dependent? 327. Yes
17. How many high energy phosphate bonds are required for FA activation in their oxidative catabolism? 17. 2
628. What does skeletal muscle export in prolonged exercise? 628. Lactate
388. What inhibits CPS II? Activates? 388. UDP/UTP, PRPP
644. G6P DH is in what organelle? 644. ER
8. What is the major dietary lipid? 8. Triacylglycerol (TAG)
471. What is a glucogenic AA? 471. Can be made into glucose
132. What is the 4th step? 132. Dehydration
94. Describe (Briefly lipolysis) 94. TAGàFFAàAcylCoA & glycerol
614. What is kernicterus in newborns? 614. Serum bilirubin greater than 15-20mg/dl àunconjugated BR deposited in basal ganglia and causes brain damage (loss of moro reflex, lethargy, encephalopathy can result), treatment is phototherapy or exchange transfusion
620. What is iron bound to in the liver or intestinal cells? 620. Hemosiderin or ferritin
158. What determines which eicosanoid will be made? 158. Cell signaling, which cell synthesis is taking place in(IE: plateletsàthromboxane, endothelial cells PGE2,PGI2 which inhibit platelet aggregation)
504. What can these AA’s generate via transamination rxn? 504. Alphaketovalerate, alpha keto beta methylvalerate, alphaketoisocaproate
50. How is a FA transported across the mitochondrial membrane? 50. Transport coupled to carnitine (which is mt. membrane soluble)
395. What reduces sulfhydryl groups to restore activity of RR? 395. Thiredoxin reductase via NADPH (alternative is GSSG)
391. What hydroxyl is removed via RR? 391. 2’
374. What are the pyrimidines? 374. C,T,U (single ring bases)
347. What is the second step in the pathway? 347. RPP to 5-phosphoribosyl-1amine using GPAT, this is the commited step, also inhibited by ADP/GDP
208. What are two different ways to add head groups to phosphatidic acid? 208. Activated head group (CDP-head group) or activated DAG (CDP-DAG)
515. What is heme synthesized from? 515. Acetate and Gly
603. What takes sugars off BR in the intestine? 603. Bacterial enzymes which allow for some reabsorption in the gut
25. Where are chylomicrons synthesized? 25. Intestinal epithelial cell
410. T or F: heme has a long half life 410. F
465. What is ppt’d as kidney stones? 465. Magnesium ammonium phosphate
443. What can excess NH3 do to the body? 443. Ammonia can be made into glu which can deplete brain of alphaketoglutarate causing OAA to fall and TCA to stopàcell dmg; increased Glu can lead to Gln formation which depletes Glu and GABA (NT’s); brain swelling due to osmotic pressure
307. What is the function of Apo C-II? 307. Activates LPL which hydrolyzes TG in VLDL and CM’s
41. What are some examples of polyunsaturated FA (PUFA)? 41. linoleic, linolenic, arachidonic
47. What is an antilipolytic hormone? 47. Insulin
269. What activates LXR’s? 269. Oxysterols
154. What is the regulated control step of eicosanoid synthesis? 154. Release of Ara from membrane via PLA2 or PLC
311. What is the function of LCAT? 311. Transfer of fatty acid from lecithin to free cholesterol in HDL
607. What causes prehepatic jaundice? 607. Hemolysis, abnormal Hb, autoimmune disease, etc.
506. What is homocistunria type 1 caused by? 506. cystathionine synthase deficiency (high homocystine and methionine levels)
125. T or F: in mammals all rx. By FA synthase are catalyzed by distinct separate enzymes? 125. F: these enzymes are coupled in a multi enzymatic complex known as FA synthase
486. Can cysteine inhibit cystathionase via feedback inhibition? 486. Yes
100. Name 2 KB 100. Acetoacetate, B-hydroxybutyrate
338. Describe the mechanism of atherosclerosis 338. DamageàLDL enters through broken epitheliumàLDL is oxidizedàadhesion factors expressed & monocytes bindàMacrophages have scavenger receptor to bind oxidized LDL & internalizes itàMacrophage becomes overloaded with LDL and is now called foam cellàcytokines etc. form plaque on endothelial layer & produce metalloproteinases that can break down collagen, platelets bind and initiate thrombus that can cause MI
64. What is the fourth step of β-oxidation? 64. β-ketothiolase (cleaves terminal Acyl-CoA), reverse claisen condensation, thioester attached to ketone of beta carbon is good for nucleophilic attack
446. Where are the 2 enzymes aforementioned located? 446. Mitochondria
218. Describe formation of ether glycerolipid 218. Ether chain replaces ester chain on DHAP with alkyl substituent extension, activated headgroup then added on at expense of phosphate groupàreduce alkyl chain using NADP àplasmalogen produced
172. What does the 3 in PGA3 mean? 172. 3 double bonds
366. What is a deficiency in adenosine monosphate deaminase associated with? 366. Myopathy
106. KB are only made where? 106. Liver
509. What does glycine contain both carbon and N2 for synthesis? 509. Heme, Creatinine, purine bases
510. What is used to make creatinine? 510. Glycine (kidney) arginine (liver)
530. What does Epi break down to be excreted in urine? 530. Vanillyl mandelic acid
294. What can vitamin D deficiency lead to ? 294. Rickets in children and osteomalacia in adults
565. What could increased ALA in urine be diagnostic for? 565. Lead poisoning
425. What are the purely ketogenic AA’s? 425. Leuceine, lysine
586. What enzyme breaks the heme ring open? 586. Heme oxygenase
229. What tissues are glycolipids and sphingomyelin found in (mainly)? 229. Neural tissue
111. How are hepatic TAG exported from liver? 111. VLDL
15. How much (percentage) of the bile salt pool is excreted? 15. 5%
467. What are some treatments for urea cycle enzymes? 467. Low protein intake (replace with a-ketoacids), remove excess ammonia by using levulose to kill ammonia producing bacteria, administer sodium benzoate,etc.
541. Do poryphyrinogens have color? 541. No, but poryphins do
487. What does a deficiency in cystathionase lead to? 487. Cystathionuria (benign disorder)
485. The sulfhydryl groups of cysteine can be oxidized to form what which generate sulfated proteoglycans 485. PAPs
555. What is the first step in heme synthesis 555. D-aminolevulinic acid is formed from glycine and succinyl CoA in mitochondria via ALA synthase and transported into cytosol
339. T or F: A stable atherosclerotic plaque has a thin fibrous cap. 339. F
266. What class of drugs inhibits HMG CoA reductase? 266. Statins
582. What is acute intermittent porphyria? 582. Hepatic uroporphyrinogen I synthase deficiency, PBG and ALA accumulate in urineàdark urine, heme synthesis reduced, ALA is upregulated since heme levels are low, neurological symptoms but not photosensitive
191. What systems are compounds produced from CytP450 pathway via ArA found in 191. Ocular, vascular, endocrine, renal (inhibit NaK ATPase)
585. What happens to heme? 585. Gets excreted and causes the colors in excrements
88. What type of oxidation is used in peroxisome? What disease is correlated with a defect in this? 88. Alpha oxidation, Refsun’s disease
528. How is Tyr converted to Norepi? 528. TyràL DopaàDopaàNorepi
226. T or F: glycolipids are a component of cell membranes 226. T
349. What is the 3rd step of purine synthesis? 349. GAR synthetase to add glycine onto phosphoribosyl amine to make GAR
451. What is the overall reaction eqn. for urea cycle? 451. NH4+bicarbonate+amino group of Asp+ATPàurea+fumarate+ADP+AMP+PPi
477. What is the condition caused by defective transaminase in Gly metabolism? 477. Oxaluria type I (due to less conversion of glyoxylate back to Gly and accumulation of glyoxylate)
303. What are the functions of ApoB-48? 303. Intestinal form, essential for CM packing and secretion, lacks LDLR
558. What is the regulated step in heme synthesis? 558. ALA synthase
505. What are branched chain AA’s ultimately converted to? 505. propionylCoa or Acetyl CoA
342. What is the difference between a nucleotide and nucleoside? 342. Nucleotide has phosphate groups, side does not
183. What are some PG’s & thromboxanes that PGH2 gives rise to? 183. PGI2, prostacyclin, thromboxanes, PGF2alpha
548. What links the pyrrole rings? 548. Methylene bridges
390. What substrate does ribonucleotide reductase work on? 390. NDP’s
377. What two compounds form the pyrimidine ring primarily? 377. Carbomoyl phosphate and aspartate
231. Do glycolipids contain a phosphate group? 231. No
192. What backbone do glycerolipids have? 192. Glycerol
320. Where are FA re-esterefied? 320. ER
524. Is type 2 as severe as 1? 524. No
123. T or F: Phosphorylated ACC is the active form 123. F, ACC is pophorylated by AMP activated protein kinase (when energy is low)àstop synthesis b/c we need energy
463. What is treatment for argininosuccinase deficiency? 463. Increased arginine, reduced protein intake
321. Where are CM’s assembled? 321. ER
188. What increases vascular permeability, T cell proliferation, eukocyte aggregation and IL-1,IL-2? 188. LTB4
393. Describe the structure of RR 393. Tetramer, one active site, has specificity and activity site
1. What is a lipid? 1. Water insoluble biological compound soluble in fat solvents
31. Where does the released FA travel to? 31. Muscles, adipose tissue, etc.
267. What receptor regulates cholesterol synthesis and storage? 267. LDL receptor
630. What are the substrates for Glycogenesis? 630. Glc 1 phosphate, Glc
495. What is the treatment for PKU? 495. Diet low in Phe, rich in Tyr
52. How are FA’s activated in order to form FA-CoA 52. FA-CoA synthetase claves ATP to AMP (2 high energy bonds) to produce FA-CoA and pyrophosphate (uses the energy from repulsion,entropy,resonance of ATP to form a high energy thioester bond, energy is conserve)
330. Describe reverse cholesterol transport 330. SRB1 removes cholesterol and stores in hepatocyteàABCA1/ApoA1 form pre beta HDL which takes up cholesterol from peripheral tissues (ABCA1/G1 fxn) and esterfies cholesterol and HDL molecules via LCAT for transfer back to liver
422. How does penicillamine alleviate cystinuria? 422. Reacts with one Cys to form cys-penicillamine
543. What contains most of the body’s heme? 543. Hemoglobin
148. What enhances aggregation of PGE2 and PGI2 from endothelial cells to inhibit bleeding? 148. Thromboxanes
500. Where does the aromatic ring of Trp end up via degradation pathways? 500. NAD/NADP
42. What bond is cleaved in beta-oxidation? 42. α-β bond (by standard organic chemistry nomenclature convention)
18. What carries FA into the lymphatic system? 18. Chylomicrons
65. How many rounds of β-oxidation to completely breakdown oleate? 65. 8
514. What isozyme of creatinine is in muscle? Heart? Brain? 514. MM, MB, BB
252. What esterfies cholesterol for transport into chylomicrons? 252. ACAT
379. How many ATP’s does the CPS II rxn. use? 379. 2
318. What is the function of SR-BI? 318. Hepatic uptake of cholesteryl ester from HDL in reverse cholesterol transport
419. What is hartnups disease? 419. Inability to absorb neutral/aromatic AA’s
178. What is the function of PGF2α? 178. Vasoconstriction, bronchoconstriction, smooth muscle contraction
578. T or F: porphyrias are all Autosomal dominant 578. F: all except erythropoietic
80. How many ATP’s are generated by oxidation of palmitate (d16:9)? 80. 102 (loss of first round and usage of NADPH)
460. What will a defect in NAGs lead to? 460. Type 1 hyperammonemia
540. What is the precursor to porphyrin? 540. Porphyrinogen
606. What causes intrahepatic jaundice? 606. Genetic disorders, hepatitis, newborn jaundice, chemical/drugs, Tylenol
618. Where is most iron present at in vivo? 618. Hb
55. What is the method of transport for short and medium chain FA’s into the mt.? 55. Diffusion
189. What increases vascular permeability and bronchoconstriction (in lipoxygenase pathway) 189. LTC4,LTD4
152. Eicosanoids are produced from ____________ phospholipids. 152. Membrane
285. What is the most potent gluccocorticoid? What are some of its effects? 285. Cortisol, anti inflammatory, stimulates GNG, sodium retention
610. High BR and high conjugated BR would be diagnostic of ? 610. Post hepatic jaundice (also dx. by high conjugated BR in urine and no urobilinogen)
251. What helps reflux cholesterol back into the small intestinal lumen and excludes plant sterols from entering chylomicrons? 251. ABCG5/ABCG8
236. Where does synthesis of glycolipids take place? 236. ER and Golgi (Sequentially adds glycosyl residues, sulfate transferred from PAPs)
574. What enzyme adds lead to protoporphyrin IX? 574. Ferrochelatase (makes heme)
445. What enzyme adds carbomyl onto ornithine? 445. Ornithine transcarbamolase
417. What are 3 ways AA’s are absorbed? 417. Sodium cotransport, facilitated transport, g-glutamyl cycle
275. What is the purpose of LXR’s upregulating HDL’s? 275. Return cholesterol from peripheral tissues to liver
341. What are some functions of nucleotides/sides? 341. Nucleic acids, energy metabolism, cellular 2nd messengers,etc.
523. What is a type of oculocutaneous albinism found on chromosome 15? 523. Type 2
481. Met is degraded to generate what product (via methyltransferase) 481. Homocysteine
176. What does C15 contain on PG’s? 176. Hydroxyl group
403. What is a suicide inhibitor of thymidylate synthase? 403. Fluorodeoxyuridylate, since fluorine is very electronegative it is a poor leaving group (its valence reaches stability in the rx. mechanism)
225. Describe ceramide synthesis 225. Palmitoyl coa +serineàsphingosineàreduction using NAPDH àdihydrosphingosineàFaCoAà oxidation to form double bond using FADàceramide
322. Where is the final processing of apolipoproteins/lipids for basolateral secretion? 322. Golgi
427. What funnels amino groups into glutamate? 427. Transamination reactions
351. In the following step after SAICAIR what TCA intermediate is produced? 351. Fumarate (from the aspartate added on)
594. What converts biilverdin to bilirubin? 594. Biliverdin reductase in macrophages
566. What else could be diagnostic? 566. Decreased prophobilinogen (product of ALA dehydratase)
217. PAF? 217. Ether glycerolipids, causes platelet aggregation, edema and hypotension
306. What is the function of Apo A-IV? 306. May activate LCAT, lots of functions, decreases eating behavior, prevents artherosclerosis, packing of lipid into CM
27. Where is the TG resynthesized? 27. Intestinal epithelial cell
97. What cycle recycles lactate/glucose from muscle/liver? 97. Cori Cycle
632. What cycle transports lactate and glucose between RBC’s and the liver? 632. Cori cycle
382. What enzyme adds asparte to the pyrimidine ring? 382. ATCase
522. What is tyrosinase related alibinism called? 522. Type 1 oculocutaneous albinism (on chromosome 11)
34. Are fatty acids a source of energy for all tissues? 34. No
281. How much bile acids are excreted per day? 281. 0.2-0.6g/d
215. Can P lipid metabolism release ArA? 215. Yes—a precursor to eicosonaoids
199. What is the chemical structure of bile salts? 199. Modified Cholesterol
573. What converts protoporphyrinogen IX into protoporhhyrin IX? 573. Dehydration to form a conjugated system (antibonding orbital overlap & color)
520. What are three things Tyr is a precursor to? 520. Pigments-melanin, T4 and T3 hormones, catecholamines
629. What are the substrates for gluconeogenesis? 629. Lactate, alanine, glycerol
589. What makes bilirubin more soluble for excretion? 589. Sugar glycosylation
140. What is different about the elongation rx. Vs. FA synthase? 140. Elongation occurs while FA is bound to CoA rather than ACP
386. How is UTP converted to CTP? 386. Amidation at 4 position using Gln (therefore can be inhibited by azaserine)
592. Where are erythrocytes processed? 592. Spleen, liver, blood marrow
179. What is released from platelets at wounds (relating to this lecture)? 179. Thromboxane A2 (TXA2)
37. What pathway oxidizes FA? 37. β-oxidation
96. In order to get G3P in fat cells we must start with what precursor? 96. Glucose, Adipose doesn’t have GNG enzymes
581. How does a porphyria defect after formation of prophyrinogens present? 581. Oxidation of porphyrinogens in skin resulting in cutaneous photosensitivity
177. What are the functions of PGI2, PGE2, and PGD2? 177. Vasodilation, cAMP, decreases platelet aggregation, leukocyte aggregation, IL-1, IL-2 and T cell proliferation & lymphocyte migration
479. Degradation of what other AA other than Ser can generate Gly? 479. Thr
492. How is tyrosine synthesized? 492. From Phe via hydroxylation reaction using oxygen and tetrahydrobiopterin
5. What is the name for a 16C saturated FA? 5. Palmitic acid (ionized form = palmitate)
145. What are some functions of eicosanoids? 145. Regulators of cell fxn, hormones
263. How many carbons does cholesterol have? 263. 27
116. What reducing equivalent does FA synthase complex use for FA synthesis? 116. NADPH
160. What does lipooxygenase form via Ara? 160. Leukotrienes
84. What is different in oxidation of odd chain FA? 84. Production of propionyl CoA upon terminal rx of beta ox àpropionyl CoA carboxylase (uses 1ATP for AMP) to produce methylmalony CoA via an epimeraseàmutase to produce succinyl CoA à run it through TCA for 1 GTP, 1 FADH2 and 1 NADH (basically lose 2NADH from AKG DH,isocitrate DH)
107. How can KB be broken down? 107. Succinyl CoA acetoacetate CoA transferase adding CoA onto acetoacetate (acetoacetylCoA) which can be broken down into two acetyl CoA’s
527. What does iodination of Tyr in thyroglobulin lead to? 527. T4/T3
483. What can homocysteine be then converted into? 483. Back to Met or into cysteine via cystathionase
584. Do we re-use the components of heme? 584. No
532. What are some functions of catecholamines? 532. Increase BP, HR,RR, muscle strength, etc.
408. T or F: AA’s maintain blood pH levels 408. T
588. Where does most of heme breakdown occur? 588. Liver
549. What types of groups do the porphyrin rings have attached to them in Heme B? 549. Propionyl acid, methyl, vinyl groups
28. Where are nascent chylomicons? 28. Lymph
605. What causes post hepatic jaundice? 605. Gallstones, drugs, inflammation, cancer, etc.
139. Where does further elongation occur? 139. ER
151. What are precursors of Eicosanoids derived from? 151. PUFA’s
102. What enzyme forms HMG CoA? 102. HMG CoA synthase
411. T or F: collagen has a long half life 411. T
457. What type is late onset with liver cirrhosis? 457. Type II
598. How many glucuronic acids are conjugated to bilirubin? 598. 2 (major form)
256. What would a mutation in ABCG8/ABCG5 lead to? 256. Inability to exclude plant sterols
46. What two hormones increase cAMP levels and in turn lipolysis (via PKA actions on Hormone sensitive lipase)? 46. Glucagon, Epi
181. What provides reducing power for the peroxidase activity of prostaglandin synthase? 181. Glutathione (GSSG,GSH)
400. What form must cytidine be in to be a substrate for thymidylate synthesis? 400. dCMP to make dTMP
122. What is the first committed step of FA synthesis? 122. Acetyl Coa carboxylase (also uses biotin cofactor) takes carbon dioxide and adds to acetyl CoA to make malonyl CoA while cleaving ATP to ADP
283. What is the precursor for all steroid hormones? 283. Cholesterol
440. What sites in the body is NH4+ released? 440. Liver and kidney
62. Describe the action of glucagon on lipolysis 62. Glucagon receptoràGsàACàcAMP via ATPàPKAàhormone sensitive lipase and perilipins phosphorylatedàdegradation of TAG
76. How many ATP’s are generated by oxidation of a saturated 16 C FA? 76. 7 FADH2 x 1.5, 7 NADH x 2.5, 8 AcetylCoA x 10, - 2 ATP = 106 ATP
461. How can we treat hyperammonemia? 461. Benzoate, pheylacetateàremoves gly and Gln causes cell to utilize NH3 to resynthesize them
333. Total cholesterol =300 mg/dL, HDL= 100 , TG=100, what is LDL (mg/dL) 333. 180
128. What is ACP attached to? 128. Pantothenic acid
219. What is 2-acetyl and 1-alkyl derivative of ethanolamine plasmalogen (saturated alkyl chain) 219. Platelet activating factor (remember it has a 2-acetyl group!)
241. What is a gangliosidose caused by deficiency in alpha-galactosidase A? 241. Fabry’s (x-linked recessive, accumulation of globsides[trihexosylceramide], kidney, heart failure, burning pain in lower extremeties)
213. What can CDP-DAG also form? 213. PIP2, and phophsatidylinositol
576. T or F: low concentrations of heme increase ALA synthase levels 576. T
557. How many steps occur in the cytosol? 557. Steps 2,3,4
454. Name two sources for NH3 in urea cycle 454. Glutamine via glutaminase, alanine via ALT
472. What are the purely ketogenic AA’s? 472. Leucine/Lysine
114. What does FA synthesis use to build FA chains primarily? 114. Acetyl CoA, malonyl CoA, NADPH, FADH2, also requires pantotheic acid for FA synthase complex
210. What are some examples of head group addition using activated DAG? 210. Phosphatidylinositol, cardiolipin, phosphatidylglycerol
289. What is the main defect in congenital adrenal hyperplasia? 289. 21-beta-hydroxylase deficiency (deficiency in mineralcorticoids and glucocorticoids) less inhibition of ACTH by cortisol more shunting through pathway and more androgens produced (masculinization of female infants)
108. What regulates ketone synthesis? 108. Availability of FA (malonyl CoA inhibits CPT1)
304. What is the function of Apo A-1? 304. Major apolipoprotein of HDL, co factor for LCAT which esterfies free cholesterol into HDL’s
561. How is ALA synthase regulated (3 ways) 561. Allosteric feedback by heme, transcriptional regulation by high or low levels of heme, inhibition of transport of pre-ala synthase from cytosol to mitochondria
168. What is the mechanism of PGE,PGD,PGI? 168. ACàcAMPàPKA
101. In KB synthesis what removes CoA to allow 2 AcetylCoA’s to be joined? 101. Thiolase
207. Where does PLA1 cleave? PLA2? PLC? PLD? 207. Ester linkage of first acyl chain, ester linkage of 2nd acyl chain, phosphate group linkage to C3, phosphate linkage to head group
117. How do FA leave liver? How are they released? 117. VLDL via lipoprotein lipase
260. What is the initial substrate for cholesterol synthesis? 260. Acetyl CoA
43. What FA can humans not synthesize, thus require in diet? 43. ω-3,ω-6
636. What is the major anabolic hormone? 636. Insulin
255. T or F: ABCG8 and ABCG5 are transcribed in the same direction 255. F
453. How is most nitrogen carried in blood? 453. Glutamine
635. When do ketones become the primary source of fuel for the brain? 635. 20-40 day starvation
56. What is the method of transport for long chain FA’s into the mt.? 56. Carnitine transport
354. What do deficiencies in the gene for ADSL cause? 354. Succinylpurinemic autism
79. How many ATP’s are generated by oxidation of a saturated 109 C FA? 79. 757, so how do I get these #? Use the formula 2(N-2)+5N-2 for any saturated FA where N = # of carbons
61. What is the second step of β-oxidation 61. Hydration via enoy CoA hydratase
450. Where do steps 3-5 take place? 450. Cytosol
575. What can inhibit ferrochelatase? 575. Lead
222. How is a FA attached to a sphingosine backbone? 222. Amide linkage
156. What does prostaglandin synthase make from Ara? 156. PGH2
282. What are the three components that give us a critical micellar concentration? 282. Cholesterol, lecithin, bile salts
202. What is an intermediate in TG synthesis? 202. Glycerophospholipid
412. What are some factors affecting the rates of protein degradation? 412. Glucocorticoids (increase degradation), thyroid hormones (protein turnover), insulin (protein synthesis), lysosomes (proteolysis), denaturation
301. What role do apolipoproteins have? 301. Assembly,secretion, peripheral metabolism and clearance of lipoproteins
254. What is the secondary structure of ABCG5/ABCG8? 254. Heterodimer
38. How are FA transported? 38. bound to serum albumin
169. What is the mechanism of PGF2 &TXA2? 169. PLCàDAG,IP3àCalcium
77. How many ATP’s are generated by oxidation of a saturated 22 C FA? 77. 148
621. What transports iron in the serum? 621. Transferrin
413. What are 4 AA’s degraded via the ubiquitin protesome pathway? 413. P,E,S,T
81. What is the major control of FA oxidation? 81. Availability of FA
459. What synthesizes the answer to #458? 459. N-acetyl glutamate synthetase (NAGS)
375. What is the branchpoint in pyrimidine synthesis (similar to what was seen for IMP in purine synthesis)? 375. UMP
141. What is the most common elongation rx.? 141. Stearate from palmitate
356. How many ATP equivalents to make GMP? AMP? 356. 8 and 7 respectively
104. If cellular NADH is high what can acetoacetate become? 104. Β-hydroxybutyrate via B-hydroxybutyrate DH using NADH
196. What FA are significant in milk? 196. Butyric, Capric (C4 and C10)
203. Can Adipose tissue directly phosphorylate glycerol? 203. No, it does not have glycerol kinase
308. What is the function of Apo-E? 308. Ligand for hepatic chylomicron remant receptor and LDL receptor
428. Transamination moves an amino group from an AA to what? 428. Alpha keto acid
631. How many days after starvation do ketone body levels significantly rise? 631. 2
542. What two substrates does heme arrive from? 542. Gly and succinyl CoA
519. What are some functions of NO? 519. Vasodilation, neurotransmitter, helps in respiratory burst of macrophages, inhibits platelet aggregation
402. What inhibits thymidylate synthase? 402. Methotrexate etc. (inhibits N5,10 THF out by causing inhibition of dihydrofolate reductase)
559. What is a cofactor for ALA synthase? 559. PLP (Vit. B6)
550. T or F: porphyrinogens are reduced porphyrins 550. T
312. What activates LCAT? 312. Apo A1
314. What is the rate limiting step of cholesterol synthesis? 314. HMG CoA reductase
521. What causes albinism? 521. Deficiency of tyrosinase, (defect in melanin synthesis pathway)
212. What forms cardiolipin? 212. CDP-DAG being joined with P-Glycerol to form diphosphatidylglycerol
163. What are potential stimuli for releasing Ara from membrane? 163. Epi, thrombin, AGII which activate PLA2 and other lipases
380. Where is CPS I used? 380. Urea cycle in mitochondria
590. What could be some causes of hyperbilirubinemia? 590. High RBC turnover, blockage of bile channels, physiological jaundice of newborn, etc.
85. What vitamin does methylmalonyl coa mutase require? 85. B12 (corrin ring structure)
299. Which lipoprotein transports most of the cholesterol? 299. LDL
133. What is the 5th step? 133. Reduction of double bond using NADPH
361. What activates GPAT? 361. PRPP
407. How are all of the active sites for ATcase, dihydroorotase, dihydroorotase DH assembled? 407. On one peptide (substrate channeling)
45. Describe hepatic glycerol metabolism. 45. Gycerol kinase phosphorylates glycerol to glycerol 3 phosphateàG3P DHàGNG
368. How can excess bases be scavenged? 368. HGPRT, APRT can combine PRPP with bases to form IMP,AMP,GMP
268. What is the function of LXR’s? 268. Put cholesterol in a safer place by transcriptional regulation of key intermediates/enzymes (avoids cholesterol overload)
431. What does glutamate and oxaloacetate produce via AST? 431. Alphaketoglutarate and aspartate
173. Describe the structure of a PG 173. Pentyl ring with 2 acyl chains
567. What two enzymes are needed to form heme from prophobilinogen? 567. Uroporyphyrinogen I synthase & cosynthase, & porphyobilinogen deaminase (forms 4 pyrrole rings)
363. What enzyme in purine degradation deficiency can cause SCID? 363. Adenosine deaminase (dATP inhibits DNA synthesis and kills rapidly proliferating cells such as lymphocytes)
3. Give some examples of lipids 3. Fatty acids, TAG, TG, cholesterol, membrane phospholipids, steroid hormones, etc.
544. What type of Heme is in Hb? 544. D
258. What drug inhibits NPC1L1? 258. Ezetimibe
577. What are the two types of porphyrias 577. Erythropoietic & hepatic
298. Which lipoprotein is the largest in size? 298. CM
646. A sailor has been fasted for 7 days, the suddenly jumps overboard to swim to shore, where does his fuel come from? 646. Muscle glycogen, (used during periods of exertion or maximal activity, if it was a slow relaxed swim it might have been fatty acids or ketones)
11. What protein binds to lipase and stabilizes it by displacing a bile salt in a micelle? 11. Colipase
239. What is a disease caused by absence of hexoaminidase A? 239. Tay Sach’s (GM2 ganglioside accumulates, neurodegeneration, common in Ashkenazi jews)
184. Is aspirin a covalent modification on PS? 184. Yes but ibuprofen and Tylenol are not (competitive inhibitors)
508. What are some major effects of histamine? 508. major mediator of allergic response via mast cells, constricts lungs in bronchospasms, releases HCl in stomach, excitatory neurotransmitter in brain
214. What is the main component of surfactant? 214. Dipalmitoylphosphatidylcholine (reduces surface tension)
240. What is a gangliosidose caused by deficiency in Beta-glucosidase? 240. Gauchers (glucocerebroside accumulates, Autosomal recessive)
310. What is the function of HL? 310. Remnant lipoprotein uptake, attached to heparin sulfate PG on hepatocytes
476. By enzymatic action of an oxidase what can glycine become? 476. Glyoxalate
317. What is the function of LRP? 317. Heptake uptake of remnant CM
261. Describe briefly, cholesterol synthesis 261. Acetyl coa àacetoacetyl CoA via acetyl CoA thiolaseà3-hydroxy-3methylgutaryl CoA (HMG CoA) via HMG CoA synthaseàMevalonate via HMG CoA reductase (regulated, commited step) using 2NADPHà3 mevalonates form farnesyl pyrophosphate via a series of stepsà2 farnesyl pyrophosphates joined to make squalene (30 carbon precursor)àvarious decarboxylations etc. to make dcholesterol (27 carbon)
33. Does the same glycerol cleaved take part in TAG resynthesis for instance in adipocytes? 33. No, it’s a new glycerol molecule
640. T or F: glucagon increases ketogenesis 640. T
137. Beginning with ACetylCoA only? 137. Have to form Malonyl CoA’s à need 7 ATP’s in addition and 7 CO2’s to what is in the answer to #137
150. What bonds are unsatured in arachidonic acid? 150. 5,8,11,14
235. What is an example of a ganglioside? 235. Ceramide-glc-gal, GM1,GM2
90. What is the most common sort of deficiencies in FA oxidation? 90. Oxidation of MCAD’s: treatment is to avoid fasting, eat meals with less fat to control lipolysis and decrease dependence on ketones
583. Would barbiturates help a AIP patient? 583. No it would stimulate ALA synthase and worsen the problem by making more ALA and PBG
444. What enzyme in the Urea cycle adds nitrogen onto bicarbonate? 444. CPSI using ATP
538. How is melatonin synthesized from serotonin? 538. Acetylation via acetylCoA and methylation via SAM
93. Second largest source? 93. Proteins
186. What is the fxn. Of lipoxygenase? 186. Incorporate oxygen into double bond of ArA forming hydroperoxy group which isomerizes to hydroxyl
4. Describe the structure of a fatty acid 4. Long chain carboxylic acid
26. Where is a TG converted to 2-MG or FA ? (free fatty acids) 26. Intestinal lumen
273. Are CYP7A and ABCG5/ABCG8 upregulated by LXR’s? 273. Yes
497. What does a defect in this step cause? 497. Tyrosinemia II (eye, skin, lesions, neurological disorders) àlow tyr and low phe diet is treatment
434. T or F: glutamate is a neurotransmitter 434. T
35. How much energy does oxidation of fat yield? 35. 9kcal/g
175. Where is the carboxyl group located on PG? 175. C1
126. What portion of FA synthase attaches to FA synthesis intermediates? 126. ACP portion has phopspho-pantetheinyl prosthetic group (two sulfhydryl groups)
518. What is nitric oxide formed from? 518. Arginine using nitric oxide synthase (NOS) (requires NADPH and oxygen)
309. What activates LPL? 309. Apo CII
24. What organelle is responsible for apo particle maturation and secetion? 24. Golgi
247. How much cholesterol is absorbed from the small intestine? 247. 70%
491. Can our bodies synthesize aromatic rings? 491. No (makes them essential AA’s)
66. How many rounds of β-oxidation to completely breakdown palmitate? 66. 7
30. What activates mature CM? 30. LPL
49. What are long chain FA’s carried on in the blood? 49. Serum albumin
537. What have low levels of serotonin been associated with? 537. OCD, migraine, IBS, tinnitus, fibromyalgia,etc.
134. How is the malonyl CoA transferred to AcetylCoA? 134. CH2 group binds to carbonyl of acetyl group forming B-keto intermediate
124. What long term regulation is ACC under? 124. Transcriptional regulation
209. What are some examples of head group addition using activate head groups? 209. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine
553. What organelle does heme synthesis begin and end in? 553. Mitochondria (succinyl CoA) goes into cytoplasm then back into mitochondria
496. What is the first step in degradation of tyrosine? 496. Removal of ammonia via tyrosine aminotransferase
16. How is a FA activated? 16. Acylated by addition of CoAsh (high energy thioester) utilizing ATP to AMP, produces FA-CoA
265. What are some factors that effect HMG CoA reductase? 265. Insulin (+), glucagon (-), thyroid hormone (+), cortisol (-), intracellular HMG CoA reductase levels, and intracellular cholesterol levels
432. If there is an abnormal increase in the substrates for these reactions (AST and ALT) what organ is in failure? 432. Liver
272. Is NPC1L1 upregulated by LXR’s? 272. No, downregulated (takes less cholesterol up)
601. What is the purpose of conjugation? 601. Make BR more soluble for secretion into bile ducts
611. What is found in the urine in post hepatic jaundice? 611. Conjugated BR, not urobilinogen since it is bypassing intestines from liver and only comes from blood stream
51. What happens to FA in the mitochondria? 51. Oxidizing environment, NAD is high relative to NADHà rx. Favoring reducing equivalents favored and NADH/FADH2 produced for energy utilization via CAC,ETC, KB,etc.
371. Can high levels of urate be useful to humans (evolutionarily)? 371. Yes, prevents oxidative damage & allows us to senesce
249. How is circulating cholesterol transported? 249. In lipoproteins with cholesterol on surface and cholesteryl esters in the core
10. What digests TG into monoacylglycerols and diacylglycerols? 10. Lipase (gastric or pancreatic)
372. What is an antagonist of GPAT that mimics Gln? 372. Azoserine
200. Where are TG resynthesized? 200. Intestinal epithelial cells
645. 20 yr old boy is starving for 30 hours, what is main source of primary fuel for brain? 645. Muscle protein
58. What are the enzymes that reversibly transport FA-CoA and Fa-Carnitine in the mt.? 58. Carnitine-palmitoyl-transferase 1 and 2 (CPT1,CPT2); CPT1 is on outer mt membrane, CPT2 is on inner membrane (reforms FA-CoA and releases carnitine inside mt.)
162. What is the control point for making eicosanoids? 162. Release of Ara from membrane (TQ)
507. What is homocystinuria type 2/3 caused by? 507. deficiency in methl-b-12 and methyl THF synthesis (high serum homocysteine and low methionine levels)
305. How is the mRNA for Apo-B edited in making B-48 instead of B-100? 305. Single base pair substation, inserts stop codon using APOBEC-1 complex that has a mooring sequence to help precisely insert A for a C
616. Does a mechanism exist to get rid of iron? 616. No (not other than sloughing off cells)
385. After ring closure what enzyme forms orotate from dihyrdoorotate? 385. Dihydroorate dehydrogenase via NAD+ (which passes e- to UQ)
405. What compounds can be used to inhibit nucleotide synthesis reactions that use Gln as a substrate? 405. Azoserine, DON (GPAT,CPS II, CPT synthase etc.)
334. Total cholesterol =300 mg/dL, HDL= 100 , TG=100, what is LDL (mmol/L) 334. 155
470. What is a ketogenic AA? 470. Can be made into AcetylCoA or acetoacetate
277. What are some characteristics of the answer to #276? 277. High plasma 7-dehydrocholesterol which is toxic, mental retardation and multiple congenital malformations
387. What activates ATcase? 387. ATP (means we have enough purine, make pyrimidinesàCTP inhibits)
384. What enzyme closes the pyrimidine ring? 384. Dihydroorotase
622. In blood what oxidation state of iron can cross plasma membrane? What oxidation form is iron stored as? 622. Fe2+, Fe3+
92. What accounts for most of energy stores in vivo? 92. TAG’s
452. How are the TCA and urea cycle linked? 452. Via fumarate and alphaketoglutarate
201. What do chylomicrons contain? 201. Cholesterol, phospholipids, TAG
358. What enzymes phosphorylate AMP/GMP? 358. Adenylate kinase, guanylate kinase
512. What is used to measure heart malfunction? Kidney malfunction? 512. Serum CK, plasma CK
423. Do pt. with hartnup or cystinuria have hyperamionacidemia? 423. No, they do not absorb them so they are not in excess in serum
71. How does free carnitine return across the membrane? 71. translocase
563. What enzyme causes two d-ALA’s to condense to form pyrrole ring? 563. ALA dehydratase which forms prophobilinogen ring
149. What are some functions of Eicosanoids (6)? 149. Inflammatory response, smooth muscle contraction, water and sodium excretion, blood pressure regulation, constrictors and dilators of BV, bronchoconstriction & bronchodilation
89. Where does omega-oxidation take place? 89. ER
545. What are some examples of hemoproteins? 545. Cytochromes, catalase, peroxidase, tryptophan
237. How are sugars activated to attach to glycolipids? 237. UDP or CMP head groups
531. What is high vanillyl mandelic acid indicative of? 531. Tumor of chromaffin cells
503. What are the branched chain AA’s? 503. Val, Ile, Leu
153. What enzyme activates arachidonic acid (Ara) ? 153. Phospholipase A2 (or PLC)
602. What is the rate limiting step of heme breakdown? 602. Conjugated BR being excreted into bile canaliculi (against concentration gradient)
171. What is the most oxidized PG? What is the 2nd most? 171. PGA, PGB (alphabetical order from most oxidized to most reduced)
438. What are Ser and Thr deaminaetd by? 438. Ser and Thr dehydratase to pyruvate & a-ketobutyrate respectively
397. If dATP is bound to RR what does this do? 397. Opposite of #396
69. Why can short and medium chain FA enter mt but not long chains? 69. …large ones are bigger à can’t diffuse..recall the pores acoss mt are membrane are selective for size
129. What is the 1st step of FA synthase? 129. Transfer of malonyl CoA to synthase (after FA synthase is primed with AcetylCoA on other sulfhydryl pantothenic acid group)
29. What forms a mature chylomicron? 29. ApoCII added by HDL+ApoE
360. What inhibits formation of AMP? GMP? 360. AMP and GMP respectively (block each of their respective pathways, feedback inhibition)
75. How are electrons transferred from FADH to ETC? 75. ETFàCoQàETC via a series of semiquinones,etc.
135. What happens after malonyl CoA transfer? 135. Reduction using NADPH to form hydroxyl on w-1 ketone to form hydroxylàdehydrationàreduction using NADPH againà now chain is saturated
166. What does HETE stand for? 166. Hydroxyeicosatetraenoic aid
110. What are FA stored as? 110. TAG
233. Are acidic glycolipids charged at neutral pH? 233. Yes
587. What enzyme makes bilirubin from biliverdin? 587. Biliverdin reductase
39. What are some examples of saturated fA? 39. palmitate (16C), stearate (18C), arachidate (20C)
418. What is re-converted to GSH in the g-glutamyl cycle? 418. Oxyproline
441. If the liver is damaged would NH3 levels rise? 441. Yes without urea cycle it would accumulate
474. Describe the pathway of glycine synthesis 474. Pyruvateàserineàglycine via PLP and THFàGly
270. What do LXR’s heterodimerize with? 270. RXR (retinoid X receptor)
346. Is this step regulated? 346. Yes, allosterically by ADP/GDP
424. What genetic defect in AA absorption is linked with cystinuria? 424. Defective Lys, ornithine, cysteine absorption
290. Describe briefly, vitamin D synthesis 290. Converted to vitamin D3 from 7dehydroxy cholesterol in malpighian layer of skinàundergoes hydroxylation at C25 in liver and C1 in kidney to form 1,25 dihydroxycholecaciferol
57. Where are very long chain FA’s oxidized? 57. Peroxisome
501. Where does the carbon skeleton of Trp end up? 501. Ala
83. What is different in oxidation of unsaturated FA? 83. Isomerizes from cis unconjugated double bonds via enoylCoA isomerae to trans, cisàcontinue beta oxàreduce conjugated double bond via 2,4 dienoyl CoA reductase (uses NADPH) and produces trans d3 and is then isomerized into trans d2
448. What is the 4th step? 448. Arginnosuccinase to cleave fumarate from argininosuccinate
404. What are some examples of methyl xanthine stimulators? 404. Chocolate, coffee, etc. (increase cAMP by inhibiting phosphodiesterase)
278. How can we treat the answer to #276? 278. Feed cholesterol which can feedback inhibit HMG CoA reductase, or use statins
120. Describe the citrate cycle 120. Citrate Synthase (OAA+AcCoA)àCitrate lyase (now in cytosol, to reproduce OAA and AcCoA) using ATPàMalate DH makes malate from OAA àmalic enzyme produces NADPH or FA synthesisàpyruvate carboxylaseàback to OAA (logic is to keep NAD/NADP pools distinct in cell)
570. What decarboxylates side chains of uroporphyriongen? 570. Uroporphyriongen decarboxylase (makes acetate groups into methyl groups)
429. What do all transaminases use to transfer amino groups? 429. Pyridoxyl 5’ phosphate (PLP)
98. How is nitrogen waste utilized? 98. Urea cycle
74. What is the regulated step of FA oxidation? 74. CPT1, entry into mt. recall cytosol and mt have diff. CoA pools (mt is used for ox, cyt. Is used for synthesisàcompartmentalization once we move between pools we are more or less committed to the pathway).
234. What do acidic glycolipids contain? 234. N-acetylneuraminic aid (NANA)
130. What is the 2nd step? 130. Condensation of malonyl and acyl groups
205. Describe formation of a TAG 205. Glycerol 3 phosphate formedàaddition of FA’s via glycerophosphate acyltransferase using FaCoA as substrateàphosphatidic acid is cleaved to add final FaCoA (TG synthetase complex is bound to ER)
9. What composes bile salts? 9. Cholesterol esters (planar ring structure with hydroxyl groups facing towards hydrophilic surface, and steroidal surface facing hydrophobic areas)
367. What is an inhibitor of xanthine oxidase? 367. Allopurinol (prevents uric acid from building up by instead having hypoxanthine/xanthine buildup which are more soluble), used to treat gout
638. What stimulates release of insulin? 638. Glc
398. What does the specificity site do? 398. Ensures a balanced pool of nucleotides (if we have too many purines, make pyrimidines etc.)
498. What does deficiency in homogentisate oxidase cause? 498. Alcaptonuria (accumulation of homogentisate which causes arthritis)
378. What is the regulated step for pyrimidine synthesis in Eukarya? Bacteria? 378. CPS II, ATCase
613. Describe physiological jaundice of the newborn 613. Jaundice after 2 days of birth, very common, no urinary bilirubin or uorbilinogen (no gut bacteria), bilirubin in meconium, treat by using light which isomerizes bilirubin to a less toxic form
525. Is type 3 as severe as 2? 525. No, can’t notice unless from a dark skinned family
536. T or F: Serotonin is a diamine neurotransmitter 536. F, monoamine
109. What is the goal of FA synthesis? 109. Store glucose breakdown products as FA
244. What dietary products contain cholesterol listed in lecture? 244. Meat,eggs,dairy
302. What are the functions of ApoB-100? 302. From liver, essential for VLDL packaging and secretion (contains LDLR domain)
612. What are some genetic defects that can cause post hepatic jaundice? 612. Dubin Johnson syndrome, rotor’s syndrome (disorders which can conjugate bilirubin but can’t secrete it into bile)
262. What is the total cost of cholesterol synthesis? 262. 18 moles Acetyl CoA, 36 moles ATP, 16 moles NADPH
353. What enzyme forms AMP from Inosinate by releasing fumarate? 353. Adenylosuccinate lyase (ADSL)
547. How many rings does heme B have? 547. 4 pyrrole rings (tetrapyrrole)
376. What enzyme is required to make deoxyribonucleotides? 376. Ribonucleotide reductase
415. What are the essential AA’s? 415. Arg, His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val (MILK RH FTW V)
554. T or F: heme regulates its own synthesis 554. T
580. How does a porphyria defect prior to formation of porphyrinogens present? 580. Accumulate ALA and PBG
623. If iron is not needed how is it disposed of? 623. Rapid sloughing off of intestinal cells
513. What is the main function of creatinine phosphate? 513. Store phosphate bonds as energy reserve
99. In the starved state what becomes a major souce of energy? 99. Ketone bodies from FA oxidation
469. What are all 20 AA’s able be broken down into? 469. AcetylCoA, pyruvate, 4 TCA intermediates (OAA, fumarate, succinylCoA, alphaketoglutarate)
396. If ATP is bound to RR what does this do to the enzyme? (in its activity site) 396. Turns it ON: basically says we are in a dividing state so we need more pyrimidine synthesis for DNA synthesis
599. What adds glucuronic acid to bilirubin? 599. UDP glucuronic acid via UDP glucuronyl transferase
180. What is the parent compound of other PG’s? 180. PGH2
246. What is the majority of cholesterol delivered to the small intestine from ? 246. Biliary cholesterol (800-1200mg/day)
502. Trp to NAD requires what cofactor? What does a deficiency in this cofactor cause? 502. PLP, pellagra like symptoms
639. What inhibits release of insulin? 639. Epinephrine
517. What is converted by decarboxylation of Glu? 517. GABA (using PLP)
399. What is thymines only function? 399. To make DNA
315. What is the function of ACAT? 315. Conversion of free cholesterol to cholesterol ester
389. Does CTP inhibit CPS II? 389. No (this is counterintuitive)
182. If you were treating pulmonary hypertension what PG would you use? 182. PGI2
82. What enzyme does insulin stimulate in FA synthesis? 82. ACC (Acetyl CoA carboxylase)
337. Elevalated levels of Apo (a) and Lp (a) are associated with what? 337. Promoting clot formation on atherosclerotic plaques (LDL bound to ApoA looks like kringles)
426. What is the compound that is excreted containing nitrogen? 426. Urea
296. What kind of lipoproteins are present in the liver? 296. VLDL,LDL,HDL
72. What inhibits CPT1? 72. malonyl coA a FA synthesis precursor
326. Is transfer of CM to Golgi via PCTV microtubule dependent? 326. No
335. Do lifestyle changes effect monogenic dyslipidemia’s? 335. Typically not, most require drug therapy, whereas polygenic is opposite
359. What enzymes phosphorylate nucleoside diphosphate? 359. Nucleoside diphosphate kinase
539. What is the ring in heme called? 539. Porphyrin
625. Does glycogen metabolism in muscle respond to signals from insulin/glucagon? 625. No
21. If the B –apoprotein gene is going to produce a protein destined for the liver how much of the AA transcript is transcribed? 21. 100%, thus its termed ApoB-100
478. What is a clinical condition manifested by excess glyoxylate 478. kidney stones (ppt. with calcium)
436. What enzyme deaminates aspartate? 436. AST
271. What do oxysterols indicate? 271. Amount of free cholesterol
32. Where does the glycerol travel to? 32. Liver (glycerol cycle)
250. What is the cholesterol transporter of the small intestine? 250. NPC1L1
91. What is the energy diff. in peroxisomal oxidation of FA? 91. Loss of energy from first step (still produces FADH but is not coupled to ETC since its not in mt, transfers e- instead to peroxide)
295. What is the purpose of a lipoprotein? 295. Provide a thermodynamically stable particle to transport lipid through bloodstream
350. What step adds aspartate to CAIR? 350. SAICAIR
323. Describe the pathway of FA from exogenous sources 323. Intestinal epitheliumàFABPàApoB-48 àCM via MTPàPCTVàGolgiàSecretion
138. How long of a chain does FA synthase produce? 138. 16C
95. Describe insulin/glucagon ratio in fed state. 95. High ratio
147. What is the main precursor to PG’s? What are two other minor precursors? 147. Arachidonic acid; Eicosatrienoicacid (gamma linoleic acd) & eicosapentaenoic acid
223. What is the difference between sphingolipids, glycolipid, and ceramides? 223. Sphingolipids have a p-choline group, glycolipids have carbohydrate group, ceramides don’t have a group
204. How does adipose tissue produce glycerol 3 phosphate? 204. Glucose metabolism
437. What do tumor cells require for growth that can be inhibited in these pathways? 437. Asparagine, inhibited by adding asparaginase which converts Asn to Asp
499. What does a deficiency in degradation of fumarylacetoacetate cause? 499. Tyrosinemia I (liver failure and death within 1 yr of life)
6. From which end does the numbering system using ω start? α? 6. Hydrocarbon end; Acid end
105. Acetoacetate can spontaneously decarboxylate to what ? 105. Acetone
230. What are some disease states associated with glycolipid/sphingomyelin degradation? 230. Gauchers,Tay Sachs, Fabray’s (CNS symptoms)
597. Where is bilirubin conjugated with glucuronic acid? 597. Liver
228. What makes ceramide into sphingomyelin? 228. Pshophocholine attachment
286. What senses drop in ECFV and causes release of renin? 286. Juxtaglomerular apparatus (JGA)
63. What is the third step of β-oxidation? 63. B-hydroxyacylCoA DH , oxidizes hydroxyl to ketone & produces NADH
369. What can loss of HGPRT cause? 369. Lesch Nyan syndrome (mental problems, biting, self mutilation)
381. Where does carbomoyl phosphate get its nitrogen from? 381. Gln
489. What does a deficiency in cystathionine synthase cause? 489. Homocystinemia/Homocystinuria (accumulation of homocysteine and met in brain, can cause loss in cognitive fx. , tall stature, CV disease, thrombi, emboli, etc.)
161. What does cytP450 form via Ara? 161. Epoxides
569. What is the difference between uroporphyrinogen I and III? 569. Different side groups (propionyl and acetate is reversed)
352. Where do the carbons from purines derive from? 352. Glutamine, glycine (largest contribution), aspartate
144. Can desaturases add double bond to carbon 12 from the alpha carbon? 144. No, only up to carbon 10, thus why we can’t make omega-3 and omega-6 FA’s (counting from opposite end)
170. What is the parent compound of PG’s? 170. Prostanoic acid
560. If there is a deficiency in PLP what can ensue? 560. Hypochromic anemia
284. Where are glucocorticoids produced ? mineral corticoids? Sex hormones? 284. Zona fasciulata, reticularis; zona glomerulosa; testes and ovary
619. How is the body’s iron content regulated? 619. Absorption
421. Decrease in cysteine uptake can cause? 421. Cystinuria via oxidation to cystine in urine
362. Describe purine degradation 362. AMPànucleotidaseàadenosineàadenosine deaminase to inosineànucleotide phosphorylase to hypoxanthineàxanthine oxidase to xanthine and uric acid
556. What product eventually comes back into the mitochondria? 556. Copropophyrinogen III
293. What can also stimulate induction of 1-alpha hydroxylase directly? 293. Hypocalcemia and hypophosphatemia
227. Glycolipids have a _______ backbone with ________ groups attached. 227. Ceramide, carbohydrate
552. 70% of the heme synthesized in the liver is used for what? 552. Cyt P450
36. What are fats largely ingested as? 36. TAG
224. What is a sphingolipid that forms the backbone of all other classes of sphingolipids? 224. Ceramide
113. Where does FA synthesis occur? 113. Cytosol
59. Is there a shuttle for FA-CoA? 59. If there was, why are we talking about all this carnitine transport business
571. What happens after modification of side chains? 571. Coproporphyrinogen III moves to mitochondria
248. Where are Biliary cholesterol molecules synthesized? 248. Liver
115. What TCA intermediate can be shunted for FA synthesis? How is this done? 115. Citrate by using citrate lyase to form Acetyl CoA
608. What color is conjugated BR? Unconjugated? 608. Green, yellow
319. How does HDL take cholesterol back to the liver (enzyme)? 319. Via SRBP1 (scavenger receptor B1)
291. What are some effects of vitamin D? 291. Increased absorption of calcium by transcriptional regulation of enzymes, recruits stem cells to make osteoclasts, absorbs calcium and phosphate more readily in the intestine
194. What composes a glycerophospholipid? 194. 2 FA’s glycerol and head group
19. What composes most of a chylomicron? 19. TAG’s
458. What is an activator of CPS I? 458. N-acetyl glutamate
193. What composes a TAG? 193. Glycerol and 3 FA’s
473. What are the ketogenic/glucogenic AA’s? 473. Phe/Tyr, Ile, Trp
328. Describe Exogenous CM metabolism 328. CM from intestines w/ApoB-48àE and CII attach and activate LPL, CII recycled to HDLàchylomicron remnants into Liver
127. FA synthase is a _____________ (tertiary structure) 127. Dimer
626. What does excess breakdown of protein result in ? 626. Increased ammonia
466. Where is the nitrogen in urea derived from? 466. Aspartate and ammonia
143. What kind of system does desaturases use for electron transfer in FA desaturation? 143. Iron sulfur centers using cyt b5 and cyt b5 reductase, inserts double bound at d9 (ex. Oleate from stearate)
364. What other enzyme deficiency can cause SCID? 364. Nucleoside phosphorylase (after ADA in degradative pathway, still accumulates same products)
324. What transfers lipid from ER membrane to newly translated apo B ? 324. Microsomal Triglyceride transfer protein
624. What is most of the fuel stored as in the body? 624. Fat (TAG’s etc.)
572. In the mitochondria what converts coproporphyrinogen III into protoporphyrinogen IX? 572. Decarboxylation of propionyl groups into vinyl groups
325. What is another function of MTP? 325. Transfer bulk lipid from ER membrane to lumen for further lipoprotein particle lipidation
112. What does the fatty aid synthase complex form? 112. Palmitate
332. What levels indicate risk for cholesterol? 332. 5.2mmol/L, 200mg/dL
416. Lack of a single AA can give rise to wasting disease called? 416. Kwashiorkor (causes edema due to increased osmotic pressure in interstitium)
195. What are some examples of ether glycerolipids. 195. Plasmalogens, platelet activating factor
257. Where is the maximum expression of NPC1L1 257. Proximal jejunum
494. What does a deficiency in Phe hydroxylase present as? 494. Phenylketouia (PKU), phenylpyruvate accumulates and is excreted (mental retardation, lighter skin due to impaired tyrosine synthesis)
392. Describe the flow of electrons in the RR mechanism 392. Electrons move to RR via thioredoxin/thioredoxin reductase using sulfhydryl groups which undergo reversible oxidations to form disulfide bonds that can be reduced back to SH groups (to dump electrons into nucleotide via putting H instead of O)
409. What are proteins that undergo extensive synthesis and degradation in reticulocytes? 409. Heme products
242. What is cholesterol a precursor for? 242. Bile acids, steroid formation, vitamin D, etc.
190. Are HPETE’s stable? 190. No extremely unstable and reduced rapidly to form HETE’s which can be converted to leukotrienes and lipoxins
2. What properties define whether a substance is called a lipid or not? 2. Solubility properties
60. What is the first step of β-oxidation 60. AcylCoA DH takes 2e- out into FADH2 from saturated FA, oxidizes alpha-beta carbon bond to alkene
206. Is LPL secreted in response to glucagon? 206. No, in response to insulin
475. During glycine synthesis what is a methyl group transferred to that can form carbon dioxide and ammonium ion? 475. THF
274. What are some complications of therapeutic LXR activation? 274. Hypertryglyceridimia, enhanced cholesterol esterification and storage, apoptosis and inflammation
604. What is the darkening of feces when exposed to air due to? 604. Oxidation of urobilinogens to stercobilinogens
600. What is the overall reaction of conjugating BR? 600. UDP glucose+2NAD+àUDP glucuronic acid+2 NADH +2H+
627. What does skeletal muscle export in the resting state? 627. Nothing
276. What syndrome is associated with 3-beta-delta-7hydroxylase deficiency? 276. Smith-lemli-opitz syndrome
643. What are mechanisms regulating liver metabolism? 643. Substrate supply, allosteric effects, phosphorylation, adaptive enzymes
329. Describe Endogenous CM metabolism 329. ApoB-100 CMàLDL to release FA, cholesterol recycled via ABCG1/A1
54. What nucleotide is cleaved to activate FA? 54. ATP to AMP.. if you miss this now you deserve to get it wrong
634. T or F: when a fasting person is refed it takes time for normal fed state to be re-established. 634. T
279. In infants what AA is conjugated to bile acids? Adults? 279. Taurine, glycine
401. What intermediate is used to make thymidine from cytidine 401. N5,10 THF
259. What OTC substance can we use to increase dietary sterols and inhibit cholesterol absorption thereby lowering plasma cholesterol? 259. Benecol
13. What enzyme cleaves FA from TAG at the 2 position? 13. phospholipaseA2
546. Do hemoproteins need to be synthesized constantly? 546. Yes because they have a short half life
44. Does glucagon stimulate FA synthesis? 44. no, it stimulates lipolysis
165. Describe the three main pathways for metabolism of arachidonic acid 165. COXàPG’s, Thromboxanes; Lipoxygenase àHPETEàLeukotrienes,HETE,Lipoxins; CytP450àEpoxides(diHETE, HETE)
78. How many ATP’s are generated by oxidation of a saturated 49 C FA? 78. 337
593. What is the heme ring first cleaved to? 593. Biliverdin by heme oxygenase (biliverdin is a linear tetrapyrrole)
70. Why is the AcylCoA synthetase rx irreversible? 70. Entropy, imagine trying to rearrange PPi to ATP with so very few PPi’s present (cleavage of PPi and the thioster bond is similar in free energy)
216. What class of glycerolipids are plasmalogens in? 216. Ether glycerolipids
637. What are some counterregulatory hormones to insulin? 637. Glucagon, epi, norepi, cortisol, somatostatin, GH, TH
516. What are poryphins synthesized from? 516. Gly and Succinyl CoA
331. What is the role of SREBP? 331. Bound to SCAP which measures concentration of oxytrols (indicator of cholesterol) when cholesterol is low SREBP is released and LDLR’s are upregulated, leads to increase in cholesterol levels in the cell
551. Where is heme (for hemoproteins) synthesized? 551. Erythropoietic tissues and liver
86. What is the 1st step of peroxisome oxidation of FA? 86. AcylCoa DH (makes FADH2 and peroxide)
121. What is the substrate and products of the malic enzyme rx.? 121. Malate; carbon dioxide, NADH, and pyruvate respectively
439. What is the only form of nitrogen that can pass through membranes? 439. NH3
344. What signals in the purine synthesis pathway can stimulate cell division? 344. Diadenosyl tetraphosphate, diadenosyl triphosphate
617. Where do we store iron? 617. Liver and intestinal cells
174. What constituents are on the pentyl ring at positions X and Y (C9 and C11) 174. Hydroxyl or keto group
142. Where are desaturases for FA located? 142. ER
373. How can muscle replenish TCA intermediates via purine synthesis? 373. Using ADA to form IMP which can be used via ASDL to produce fumarate