BIO250 Spr11-30

BIO250 Spr11-30 - How is it I extract strength From the...

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Unformatted text preview: How is it I extract strength From the beef I eat? - Walt Whitman Leaves of Grass (1865) 1 11.4.04 Recall: Nitrogen and Carbon Go Separate Ways 2 Fig. 18-1 11.4.04 Outline – Amino Acid Metabolism Sources and destinations of amino acids Dietary and endogenous turnover Non-essential amino acids – biosynthesis Managing the ammonia – nitrogen metabolism From tissues to liver Reactions in the liver – the urea cycle Integrative pathways – TCA, urea, and gluconeogenesis Extracting the energy – carbon catabolism Carbon entry into the TCA cycle One-carbon transfer reactions Glucogenic and ketogenic amino acids 3 11.4.04 Alternative Fates of Amino Acids Many amino acids are absorbed and used Many directly - as is - in tissue protein synthesis. For humans, 10 of the 20 natural amino acids are “essential”, and must be obtained from the must diet (“Pvt. Tim Hall”). diet Excess amino acids cannot be stored, but can Excess be oxidized for energy – carnivores derive up to 90% of their energy needs from amino acid oxidation (for people it’s 10-15%) oxidation 11.4.04 4 Except for TV, what’s the difference? 5 3eTable 18-2 Pv t . T im H al l 11.4.04 Amino Acids Not Used in Biosynthetic Reactions Undergo Oxidative Degradation Amino acids as fuel may be derived from A diet rich in protein Cellular protein turnover Abnormal protein turnover (starvation or Abnormal diabetes) diabetes) Energy comes from the α-keto acid carbon Energy -keto skeleton, after removal of the amino group, into either the TCA cycle or gluconeogenesis either Removal of the amino group (waste) requires Removal expenditure of energy expenditure 11.4.04 6 The Ten Amino Acids We Can Make The rest, we The must ingest… must Cys, Gly, Ser come from 3-phosphoglycerate 7 Fig. 18-15 11.4.04 The TCA Cycle Note a curious Note fact: each entry point for the catabolism of amino acid backbones follows an oxidation step in the cycle in 8 Fig. 16-13 11.4.04 28 Precursors for Carbon Entry to TCA 5 4 6 4 9 5 2 2 Fig. 18-15 11.4.04 Where Carbon Skeletons from Amino Acids Can Enter the TCA Cycle ASN and ASP TYR, PHE,TRP TYR, LEU, and LYS LEU, MET, VAL, ILEU, THR MET, GLN, HIS, ARG, PRO and GLU ALA, SER, CYS, GLY, THR and TYR ILE, LEU, THR and TRP TYR and PHE TYR Oxaloacetate Acetoacetyl~CoA Succinyl~CoA Succinyl α-Ketoglutarate α-Ketoglutarate Pyruvate Acetyl~CoA Fumarate Fumarate You don’t have to memorize these, but you should know the identity of the 5 main entry points to the TCA. 10 11.4.04 Extrahepatic Metabolism of Val, Ile, and Leu Fig. 18-28 The branched-chain α -keto acid dehydrogenase complex The catalyzes oxidative decarboxylation (guess how many catalyzes guess cofactors? How many proteins?) cofactors? Enzyme is phosphorylated (inactive - recall other examples?) Enzyme recall unless excess branched aa’s are present; if defective, the α-keto acids accumulate, and… 11 11.4.04 Fate of Amino Acid Carbon Skeletons The carbons of the 20 amino acids converge into the TCA The cycle (multiple entries give 28 paths), but cycle In fact, they enter it at only 5 places after each oxidation In step in the cycle step Carbons from larger amino acids may enter the TCA cycle Carbons at more than one place at Phe, Tyr, Leu, and Ile at 2 places (note relationships!) Trp (and Thr) can enter at 3 places The cell employs 2 reactions frequently Transaminations One-carbon transfers All the reactions occur in the liver, except for the branchedAll except chain amino acids: leucine, isoleucine, and valine 12 11.4.04 Overview of Carbon Flow: Glucogenic and Ketogenic Amino Acids Carbons from the pink Carbons pink amino acids can all participate in gluconeoparticipate genesis (see Ch. 14, 16) Carbons from the blue Carbons blue amino acids can all end up as acetoacetyl-CoA and, if in excess, can produce ketone bodies produce Trp, Phe, Tyr, Ile are in Trp, both categories both Only Leu and Lys are Only solely ketogenic solely 13 Fig. 18-15 11.4.04 Glucogenic vs Ketogenic Amino acids degraded to pyruvate, αAmino αketoglutarate, succinyl~CoA, fumarate, or ketoglutarate, oxaloacetate are called “glucogenic” because these intermediates can be used in gluconeogenesis gluconeogenesis Amino acids degraded to acetyl~CoA or Amino ~CoA acetoacetate are called “ketogenic”. Many fit both categories; however, leucine and lysine leucine lysine are exclusively ketogenic. are 11.4.04 14 Cofactors Involved in One-Carbon Transfers Fig. 18-16 - Most oxidized OOC- Most reduced Intermediate Aka “THF” Aka “SAM” • Three major cofactors are employed for carrying onecarbon units: biotin, SAM, and THF • Each is specific for particular oxidation states of carbon • Although THF is the most versatile, SAM is 1000x more Although reactive when methyl groups are being transferred reactive 15 You don’t need to know these structures! 11.4.04 You The Versatility of THF Fig. 18-17 10 Both N5 and N10 can carry one-carbon groups groups Or they can share 3 different oxidation different states of carbon can be carried, and be Used as donors in Used one-carbon transfers one-carbon 16 11.4.04 THF Can Add or Remove Single Carbons ria te an im ac b al s 3eFig. 18-19 • Although THF is used in both of these reactions, • Only in bacteria does the glycine α-carbon end up in the Only -carbon TCA cycle (where? What happens to the carboxyl carbon?) TCA • In animals, the α -carbon is carried off by THF In His also loses a carbon to THF (Fig. 18-26) 17 11.4.04 Can You Now Answer These Questions? 1. Why are there only 20 amino acids in proteins, 1. but 28 “paths” into the TCA cycle? but 2. For many of these “paths” the stoichiometry of 2. carbon atoms does not add up: can you name a couple of ways that these carbons are directed elsewhere? are 3. What is a “glucogenic” amino acid? 4. What is a “ketogenic” amino acid? 5. What other pathway interfaces with the latter? 6. Can an amino acid be both glucogenic and 6. ketogenic? Use an example to explain. ketogenic? 11.4.04 18 Summary of Amino Acid Oxidation - 2 Carbon skeletons end up in TCA where they can be Carbon ketogenic or glucogenic (or both) ketogenic Leu, Ile, and Val are degraded extrahepatically Amino acids only undergo partial oxidation in the liver, Amino but this can fulfill the “fed” liver ATP needs but For both making urea and for gluconeogenesis Thus, gluconeogenesis and urea synthesis can be Thus, considered parts of the same pathway, integrated with the TCA cycle: high urea synthesis reflects a high need for glucose need As with amino acid carbon catabolism, genetic defects As in the urea cycle can have serious consequences. in 11.4.04 19 What’s Wrong With This Child? Calories do not constitute nutrition… 20 11.4.04 Not All Proteins Are Created Equal (or) Why Rice and Beans? Corn Lysine Methionine Threonine Tryptophan Legumes + + Rice + Soy + + “There are no good or bad foods, just good or bad diets…” 21 11.4.04 Sources of Stored Metabolic Energy For a 70 kg male after overnight fasting… mass mass Glycogen – liver: 80 gm Glycogen – muscle: 150 gm Fat: 15,000 gm Protein: 6,000 gm But, is the protein really “stored”? 22 11.4.04 % of cal of 0.2% 0.4% 85% 14.5% Survival Value of Stored Energy 23 11.4.04 Diseases of AA Carbon Catabolism Sir Archibald Garrod discoved alkaptonuria as a genetic disease, which was nuria genetic the beginning of our understanding of “inborn errors of metabolism”… “inborn Alkaptonuria A defect in amino acid catabolism defect causes your urine to turn black Defective homogentisate 1,2dioxygenase Tyrosinemia I Defective fumaryl-acetoacetase 24 Fig. 18-23 11.4.04 Diseases of AA Carbon Catabolism Fig. 18-23 Phenylketonuria: Defective phenylDefective alanine hydroxylase Accumulation of Phe and phenylpyruvate and phenyllactate is deleterious deleterious Where might these last two come from? (Hint: see Fig. 18-25) see 25 11.4.04 Other Diseases of Amino Acid Carbon Catabolism Albinism Defective tyrosine 3-mono-oxygenase Melanin synthesis from tyrosine is blocked Affected individuals lack skin pigmentation Maple syrup urine disease Branched-chain α-ketoacid dehydrogenase Branched-chain -ketoacid (Ile, Leu, Val) (Ile, Methylmalonic acidemia [see Box 18-2!] [see Methylmalonic Methylmalonyl-CoA mutase (conversion of Methylmalonyl-CoA propionyl-CoA to succinyl-CoA) propionyl-CoA 26 11.4.04 For the final exam… Pick one genetic disease of amino acid catabolism Pick that intrigues you (except albinism, PKU, or maple syrup urine disease) and be able to articulate the information presented in Table 18-2 (except for incidence). This will be worth 15 pts. This You may include a disease not in this Table (such as You nonketotic hyperglycinemia, p. 694). nonketotic Do no more than 30 min of research on the disease, Do so that you can describe in 3 sentences or less something about the symptoms, severity, and treatment of the disease. The internet (Web MD, OMIM, etc) is a legitimate source of information – but don’t necessarily believe everything you read…! don’t 27 11.4.04 Overview: The Three Stages of Cellular Respiration Stage 1: Acetyl-CoA Stage Production from Production Glucose Fatty Acids Amino Acids Stage 2: Acetyl-CoA Stage Oxidation (TCA cycle) Oxidation Stage 3: Electron Transfer Stage & Oxidative Phosphorylation Phosphorylation Now you know what happens 28 Fig. 16-1 to the carbons! 11.4.04 ...
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This note was uploaded on 05/01/2011 for the course BIO 250 taught by Professor Culver during the Spring '08 term at Rochester.

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