Biochemistry USMLE Step 1 First Aid Flashcards

DNA
Terms Definitions
At which end of the tRNA is the aa bound?
The amino acid is covalentlybound to the 3' end of the tRNA.
Can RNA polymerase initiate chains?
Yes.
Define transition.
Substituting purine for purineor pyrimidine for pyrimidine.
Define transversion.
Substituting purine forpyrimidine or vice versa.
Define tRNA wobble.
Accurate base pairing is required only in the first 2 nucleotide positions of an mRNA codon, so codons differing in the 3rd 'wobble' position may code for the same tRNA/amino acid.
Describe DNA replication.
Origin of replication: continuous DNA synthesis on leading strand and discontinuous (Okazaki fragments) on lagging strand. Primase makes an RNA primer on which DNA polymerase can initiate replication. DNA polymerase reaches primer of preceding fragment; 5'®3' exonuclease activity of DNA polymerase I degrades RNA primer; DNA ligase seals; 3'->5' exonuclease activity of DNA polymerase 'proofreads' each added nucleotide. DNA topoisomerases create a nick in the helix to relieve supercoils.
Describe Euchromatin
Less condensed (vs.Heterochromatin), transcriptionally active.
Describe Heterochromatin
Condensed, transcriptionallyinactive
Describe key structuraldifferences between nucleotides.
1)Purines (A,G) have 2 rings.2)Pyrimidines (C,T,U) have 1 ring 3) Guanine has a ketone.4) Thymine has a methyl
Describe single-strand, excision repair.
Excision repair-specific glycosylase recognizes and removes damaged base. Endonuclease makes a break several bases to the 5' side. Exonuclease removes short stretch of nucleotides. DNA polymerase fills gap. DNA ligase seals.
Describe the difference between Eukaryotic Vs. Bacterial, viral and plasmid origin of replications
Eukaryotic genome has multiple origins of replication. Bacteria, viruses and plasmids have only one origin of replication.
Describe the main difference in eukaryotic and prokaryotic synthesis of RNA.
Eukaryotes have 3 different RNA polymerases ('I, II, III synthesize RMT') and prokaryotes have 1 RNA polymerase (which makes all 3 kinds of RNA).
Describe the method by which introns are removed from primary mRNA transcript.
Introns are precisely spliced out of primary mRNA transcripts. A lariat-shaped intermediate is formed. Small nuclear ribonucleoprotein particles (snRNP) facilitate splicing by binding to primary mRNA transcripts and formingspliceosomes.
Describe the number of bonds per purine-pyrimidine pair. Which is stronger?
G-C bond (3 H-bonds) A-T bond (2 H-bonds G-C bond is stronger
Describe the structure of Chromatin.
Condensed by (-) charged DNA looped around (+)charged histones(nucleosome bead). H1 ties the nucleosome together in a string (30 nm fiber)
Describe tRNA structure.
75-90 nucleotides, cloverleaf form, anticodon end is opposite 3' aminoacyl end. All tRNAs both eukaryotic and prokaryotic, have CCA at 3' end along with a high percentage of chemicallymodified bases. The amino acid is covalently bound to the 3' end of the tRNA.
Does RNA polymerase have a proof reading function?
No.
How do purines and pyrimidines interact, molecularly?
Purines and pyrimidines pair (A-T, G-C) via H-bonds
How does RNA polymerase II open DNA?
RNA polymerase II opens DNA at promoter site (A-T rich upstream sequence- TATAand CAAT)
How is the original RNA transcript processed in eukaryotes? (3)
1)Capping on 5' end (7- methyl G) 2)Polyadenylation on 3' end ( =200 As) 3)Splicing out of introns
In eukaryotes, what mustoccur before an newly synthesized RNA transcript leaves the nucleus?
Only processed RNA is transported out the nucleus of eukaryotes.
Name 3 types of RNA
1) mRNA 2) rRNA 3) tRNA
Name the charged histones around which (-) charged DNA loops (nucleosomecore).
H2A, H2B, H3, H4 histones
Name the enzyme responsible for the synthesis of RNA in prokaryotes.
RNA polymerase
Name the enzymes involved in ss-DNA repair. (5)
1) specific glycosylase. 2) endonuclease. 3) exonuclease. 4) DNA polymerase. 5) DNA ligase.
Name the enzymes responsible for the synthesis of eukaryotic RNA.
RNA polymerase I RNA polymerase II RNA polymerase III
What are exons?
Exons contain the actual genetic information coding for a protein
What are four types of mutations that can occur in DNA?
1) Silent 2) Missense 3) Nonsense 4) Frame shift
What are introns?
Introns are intervening noncoding segments of DNA
What are the four features of the Genetic Code?
1) Unambiguous 2) Degenerate 3) Commaless, non-overlapping 4)Universal
What atoms link aa in a protein chain?
Amino acids are linked N to C
What changes occur in DNA structure during mitosis?
In mitosis, DNA condenses to form mitotic chromosomes
What codon sequence is found at the 3' end of all tRNAs?
All tRNAs, both eukaryotic and prokaryotic, have CCA at 3' end.
What direction is DNA synthesized in?
5' --> 3'. Remember that the 5' of the incoming nucleotide bears the triphosphate (energy source for the bond). The 3' hydroxyl of the nascent chain is the target.
What direction is protein synthesized in?
Protein synthesis also proceed in the 5' to 3'
What direction is RNA synthesized in?
5' --> 3'. Remember that the 5' of the incoming nucleotide bears the triphosphate(energy source for the bond).The 3' hydroxyl of the nascent chain is the target.
What does the AUG mRNA sequence code for?
AUG codes for methionin, which may be removed before translation is completed. In prokaryotes the initial AUG codes for a formyl-methionin(f-met).
What does the P in P-site stand for? What does the A in A-site stand for?
P-site: peptidyl; A-site: aminoacyl;
What does the statement, 'the genetic code is 'commaless' mean? What is the exception to this rule?
The code is non-overlapping.The exception are some viruses.
What does the statement, 'the genetic code is degenerate' mean?
More than one codon may code for the same amino acid
What does the statement, 'the genetic code is unambiguous' mean?
Each codon specifies only one amino acid
What does the statement, 'thegenetic code is 'universal' mean? What are the exceptions (4)?
The same code is used in all lifeforms. The exceptions are;1. mitochondria, 2. archaeobacteria, 3. Mycoplasma, 4. some yeasts
What enzyme is responsible for 'charging' tRNA? How does it work?
Aminoacyl-tRNA synthetase.This enzyme (one per aa, usesATP) scrutinizes aa before and after it binds to tRNA. If incorrect, bond is hydrolyzed by synthetase. The aa-tRNA bond has energy for formation of peptide bond.
What inhibits RNA polymerase II?
alpha-amanitin inhibits RNA polymerase II
What is a conservative missense mutation?
Mutation results in a different aa encoded, but that new aa is similar in chemical structure to the original code
What is a frameshift mutation? What is usually the effect on the encoded protein?
A change in DNA resulting in misreading of all nucleotides downstream. Usually results in a truncated protein.
What is a missense mutation?
Mutation results in a different aa encoded.
What is a nonsense mutation?
A change in DNA resulting in an early stop codon.
What is a promoter?
Site where RNA polymerase and multiple other transcription factors bind to DNA upstream from gene locus.
What is a nonsense mutation?
A change in DNA resulting in an early stop codon.
What is a silent mutation?What usually causes a silent mutation?
Mutation resulting in the same aa encoded. Often the base change is in the 3rd position of the codon.
What is a snRNP? What is its function?
snRNP = small nuclear ribonucleoprotein. snRNPs facilitate splicing by binding to primary mRNA transcripts and forming spliceosomes.
What is an enhancer?
Stretch of DNA that alters gene expression by binding transcription facts. May be located close to, far from, or even within (an intron) the gene whose expression it regulates.
What is an Okazaki fragment?
The discontinuous DNA synthesized on the lagging strand during DNA replication
What is hnRNA?
hnRNA = heterogeneous nuclear RNA The initial RNA transcript is called hnRNA
What is responsible for the accuracy of amino acid selection during peptide synthesis?
Aminoacyl-tRNA synthetase and binding of charged tRNA to the codon are responsible for accuracy of amino acid selection.
What is the broad classification of nucleotides? (2)
Purines (A, G) and Pyrimidines (C, T, U)
What is the difference between hnRNA and mRNA?
hnRNA = the initial RNA transcript mRNA = capped and tailed transcript
What is the difference between thymine and uracil?
Uracil found in RNA Thymine found in DNA
What is the function of DNA ligase during DNA Replication?
DNA ligase seals synthesized DNA into a continuous strand
What is the function of DNA polymerase during DNA Replication? (2)
5'®3' exonuclease activity of DNA polymerase I degrades RNA primer; 3'®5'exonuclease activity of DNA polymerase 'proofreads' each added nucleotide.
What is the function of DNA topoisomerase during DNA Replication?
DNA topoisomerases create a nick in the helix to relieve supercoils
What is the function of primase in DNA Replication?
Primase makes an RNA primer on which DNA polymerase can initiate replication.
What is the function of RNA polymerase I?
RNA polymerase I makes rRNA
What is the function of RNA polymerase II?
RNA polymerase II makes mRNA
What is the function of RNA polymerase III?
RNA polymerase III makes tRNA
What is the mRNA initiation codon?
AUG, or rarely GUG
What is the mRNA stop codons? (3)
UGA (U Go Away) UAA (U Are Away) UAG (U Are Gone)
What is the result of 'mischarged' tRNA?
A mischarged tRNA (bound to wrong aa) reads usual codon but inserts wrong amino acid.
What is the role of endonuclease in ss-DNA repair?
Endonuclease makes a break several bases to the 5' side.
What is the role of excision repair-specific glycosylase in ss-DNA repair?
Recognizes and removes damaged base.
What is the role of exonuclease in ss-DNA repair?
Exonuclease removes short stretch of nucleotides.
What prevents an incorrect aa-tRNA pairing?
If incorrect, the aa-tRNA bond is hydrolyzed by aminoacyl-tRNA synthetase.
What prevents an incorrect aa-tRNA pairing?
If incorrect, the aa-tRNA bond is hydrolyzed by aminoacyl-tRNA synthetase.
What role does histone H1 play in chromatin structure?
H1 ties the nucleosome together in a string (30nm fiber)
What supplies the energy for formation of peptide bond?
The aa-tRNA bond has energy for formation of peptide bond.
What would most likely be the result of a mutation of the promoter sequence?
Promoter mutation commonly results in dramatic decrease in amount of gene transcribed.
When is ATP used in protein synthesis? When is GTP used in protein synthesis?
ATP is used in tRNA charging, whereas GTP is used in binding of tRNA ribosome and for translocations.
When is recombination involved in DNA repair?
If both strands are damaged, repair may proceed via recombination with undamaged homologous chromosome.
When is recombination involved in DNA repair?
If both strands are damaged, repair may proceed via recombination with undamaged homologous chromosome.
Where does RNA processing occur in eukaryotes?
RNA processing occurs in the nucleus.
Which is the largest type of RNA?
mRNA (massive)
Which is the most abundant type of RNA?
rRNA (rampant)
Which is the smallest type of RNA?
tRNA (tiny)
Which nucleotide position in the codon has room for 'wobble'?
Codons differing in the 3rd 'wobble' position may code for the same tRNA/amino acid
How do you do a Northern Blot?
Electrophorese RNA on a gel transfer to a filter expose filter to a labeled DNA probe visualize the DNA probe annealed to the desired RNA.
How do you do a Southern Blot?
Electrophorese DNA on a gel transfer to a filter and denature the DNA expose to a labeled DNA probe visualize probe annealed to desired DNA fragment
How do you do a Southwestern blot?
Separate protein by electrophoresis transfer to a filter expose to a labeled DNA probe visualize DNA bound to desired protein
How do you do a Western Blot?
Separate protein by electrophoresis transfer to a filter expose to a labeled antibody visualize Ab bound to desired protein
How do you do PCR? (4 steps)
1. Heat DNA to denature. 2. Cool DNA and let the primers aneal. 3. Heat-stable polymerase replicates DNA following each primer 4. Repeat
What are some genetic diseases detectable by PCR? (11)
SCID, Lesh-Nyhan, CF, familial hypercholesterolemia retinoblastoma, sickle cell, Bthalassemia, hemophilia A and B, von Willebrand's dz, lysosomal dz, and glycogen storage dz
What gene is involved in cystic fibrosis?
CFTR
What gene is involved in familial hypercholesterolemia?
LDL-R
What gene is involved in Lesh-Nyhan syndrome?
HGPRT
What gene is involved in retinoblastoma?
Rb
What gene/enz is involved in SCID?
adenosine deaminase
What gene is involved in Sickle cell and ?-thal?
? globin gene
What gene is involved in Sickle cell and ?-thal?
? globin gene
What is an ELISA (enzyme linked immunosorbant assay)?
Rapid lab test in which an antibody or an antigen (usually collected from a patient) is exposed to an Ag or Ab liked to to an enzyme. A positive test results in a Ag-Ab match and is usually indicated by a color change
What is PCR?
Lab procedure used to synthsize many copies of a desired fragment of DNA
Von Geirke's disease is a result of?
Glucose-6-phosphatase deficiency; also known as Type I Glycogen Storage disease
A build up of sphingomyelin and cholesterol in reticuloendothelial and parenchymal cells and tissues is found in what disease?
Niemann-Pick disease
A child is born with multiple fractures and blue sclera what is the diagnosis?
Osteogenesis imperfecta; disease of abnormal collagen synthesis resulting in fractures and translucent conn tiss over chorioid causing the blue sclera
A congenital deficiency of tyrosinase would lead to
Albinism, now can't synthesizemelanin from tyrosine
A patient presents with cataracts, hepatosplenomegaly, and mental retardation, what is the Dx?
Galactosemia
A patient presents with corneal clouding and mental retardation that is, based on family history, inherited in an Autosomal Recessive pattern, you impress your intern with a Dx of
Hurler's syndrome
A patient presents with 1.Hyperextensible skin 2.Tendency to bleed 3.Hypermobile joints, you astutely Dx them with
Ehlers-Danlos syndrome
Absence of Galactosylceramide Betagalactosidase leads to the build up of what compound in what disease
accumulation of galactocerebroside in the brain; Krabbe's disease
Absence of hexosaminidase A results in the accumulation of what molecule that is characteristic of what disease
GM2-ganglioside accumulation; Tay-Sachs disease
Albinism increase risk of developing what
skin cancer
Autosomal dominant defects will effect what members of a family
male and female
Autosomal recessive disorders often result in what kind of defect/deficiencie?
enzyme deficiencies
Autosomal recessive disorders usually effect how many generations in a family?
usually only one generation
Bloom's syndrome is characterized by sensitivity to what as a result of
sensitivity to radiation as a result of a DNA repair defect
Creatine and Urea are both made from?
Arginine
Defects in structural genes often follow what pattern of inheritance?
Autosomal dominant
Defiency of arylsulfatase A results in the accumulation of what molecule where
sulfatide in the brain, kidney, liver, and peripheral nerves. Characteristic of Metachromatic Leukodystrophy
define genetic imprinting
when differences in phenotype depend on whether the mutation is of paternal or maternal origin
define incomplete penetrance
when not all individuals with a mutant genotype show the mutant phenotype
define Linkage Disequilibrium
the tendency for certain alleles at two linked loci to occur together more often than expected by chance, as measured in a population
define pleiotropy
one gene has more than one effect on an individual's phenotype, autosomal dominant defects are often pleiotropic
Define variable expression
nature and severity of the phenotype varies from one individual to another
Fanconi's anemia is caused by what type of agents
cross-linking agents
Ganglioside is made up of what
Ceramide + oligosacharide + sialic acid
Gaucher's disease is caused by a deficiency of
Beta-glucocerebrosidase
Glucocerebroside accumulation in the brain, liver, spleen, and bone marrow are characteristic of
Gaucher's disease
Hglycine is used to make what important compound
Porphyrin which is then used to make Heme
Histamine is synthesized form what compound
Histidine
How does adenosine deaminase defiency cause SCID
Purine salvage pathway. ADA normal converts adenosine to inosine without it ATP & dATP build up inhibiting ribonucleotide reductase which prevents DNA synthesis lowering lymphocyte production
How does adenosine deaminase defiency cause SCID
Purine salvage pathway. ADA normal converts adenosine to inosine without it ATP & dATP build up inhibiting ribonucleotide reductase which prevents DNA synthesis lowering lymphocyte production
How is Lesch-Nyhan syndrome inherited and what is the result and symptoms
X-linked recessive; increase in uric acid production. Retardation, self mutalation, aggression, hyperuricemia, gout, and choreathetosis
Hunter's syndrome is characterised by what biochemical problem and how is it inherited?
deficiency of iduronate sulfatase; X-linked recessive mild form of Hurler's
In ataxia-telangiectasia DNA damage caused by what source cannot be repaired
X-rays
in G6PD deficiency the decrease in NADPH can lead to _____ if exposed to _____
hemolytic anemia; oxidizing agents ( fava beans, sulfonamides, primaquine) and antituberculosis
In PKU what builds up and what can be found in the urine?
phenyalanine builds up leading to phenylketones in the urine
In PKU, what amino acid becomes essential
tyrosine.
in the Hardy-Weinberg equation, what are the p and q and what is 2pq
p and q are each separate alleles; 2pq = heterozygote
no male to male transmission is characteristic of what type of genetic disorders?
X-linked recessive
Pompe's disease is caused by a defect in?
lysosomal alpha-1,4-glucosidase deficency
Sickle cell anemia is caused by what defect and what is it's prevalence?
AR single missense mutation in the beta globin; 1:400 blacks
Sickle cell anemia patients often present with
recurrent painful crisis and increased susceptibility to infections
Skin sensitivity to UV light secondary to a DNA repair defect is characteristic of what?
xeroderma pigmentosum
Sphingosine + fatty acid yields
ceramide
the COL1A gene mutation is associated with what disease and what type of mutation is this
Osteogenesis imperfecta;dominant negitive mutation
The main defect in Ataxiatelangiectasia is a ___
DNA repair defect
The most common form of Osteogenesis imperfecta has what genetic problem and inheritance
abnormal Collagen Type I synthesis; Autosomal dominant
the transporter for what amino acids is defective in cystinuria
COLA: Cys,Ornithine, Lysine and Arginine
Thymidine dimers are formed by exposure of DNA to UV light, are the dimers formed on the opposing strands of a DNA molecule or on the same side?
dimers are on same side
Thymidine dimers are formed by exposure of DNA to UV light, are the dimers formed on the opposing strands of a DNA molecule or on the same side?
dimers are on same side
Thymidine dimers are formed by exposure of DNA to UV light, are the dimers formed on the opposing strands of a DNA molecule or on the same side?
dimers are on same side
Thymidine dimers are formed by exposure of DNA to UV light, are the dimers formed on the opposing strands of a DNA molecule or on the same side?
dimers are on same side
Tryptophan can be used to make what three chemicals
Niacin, Serotonin, melatonin
Type III Glycogen storage disease is a deficency of ?
deficiency of debranching enzyme alpha-1,6-glucosidase
What is the cause Tx and symptoms of Lactase intolerance?
Lactase deficency; avoid diary products or add lactase pills to diet symptoms bloating, cramps, osmotic diarrhea
What % of kids born to father with mitochondrial myopathy will be effected
none! mitochondrial myopathies are inherited from mitochondria which is only inherited from the mother
What are the clinical signs of Krabbe's disease?
optic atrophy, spasticity, early death
What are the components of Cerebroside?
Ceramide + glucose/galactose
What are the components of Sphingomyelin?
Ceramide + phosphorylcholine
What are the components of sphingosine?
serine + palmitate
What are the findings and treatment of pyruvate dehydrogenase defic?
neurologic defects; increaseintake of ketogenic nutrients
What are the findings inMcArdles's disease and what is the problem?
increased glycogen in skeletal muscle due to a Glycogen phosphorylase deficency strenuous exercise cause myoglobinuria and painful cramps
What are the findings in PKU and what is the treatment?
Mental retardation, fair skin, eczema, musty body odor Tx. Decrease phenylalanin (nutrasweet) and increase tyrosine
What are the findings in Pompe's disease and what is it alternate name?
Cardiomegaly and systemic findings, leading to early death. Pompe's trashes the Pump. (Heart, Liver and muscle) Type II Glycogen storage disease
What are the findings in Von Gierke's disease?
severe fasting hypoglycemia, increased glycogen in the liver
What are the four assumptions of the Hardy-Weinberg equilibrium?
1.There's no mutation occurring at locus 2. There's no selection for any of genotypes at locus 3. Random mating 4. No migration in or out
What are the purely ketogenic amino acids?
lysine and leucine
What are the signs and symptoms of essential fructosuria?
asymptomatic, benign; Fructose appears in blood and urine
what are the signs and symptoms of Homocystinuria?
Homocysteine accumulates in urine and cystine becomes essential. Methionine and it's metabolites build up in blood. Mental retardation, osteoporosis, dislocation of the lens
What are the symptoms of Alkaptonuria?
Dark Urine from alkapton bodies; also connective tissue is dark, may have arthralgias.Bengin disease
What are the symptoms of Fructose intolerance?
hypoglycmeia, jaundice, cirrhosis
What are the symptoms of Maple syrup Urine disease?
CNS defects, mental retardation and death. Urine smells like maple syrup
What biological chemicals are derived form phenylalanine?
tyrosine; thyroxine, Dopa; dopamine NE, Epinephrine and Melanin
What causes Essential Fructosuria?
defect in fructokinase
What causes Lesch-Nyhan syndrome?
Absence of HGPRTase,(normally converts hypoxanthine to IMP and guanine to GMP) Lacks Nucleotide Salvage (LNS)- purines
What do melanin and norepinephrine have in common?
both derived directly from dopamine. Phenylalanine to tyrosine to Dopa to Dopamin
What does the term 'loss of heterozygosity' mean?
when one allele of an allele pair is lost. An example is when a patient inherits or develops a mutation in a tumor suppressor gene and the complimentary allele is then lost to deletion/ mutation. The patient would not develop the cancer until the loss of the normal allele.
What enzyme defiencies are associated with hemolytic anemia?
Glycolytic enzyme deficiencies; 1. Hexokinase2. glucose-phosphate isomerase 3. aldolase4. triose-phosphate isomerase5. phosphate-glycerate kinase enolase pyruvatekinase
What event in embryology can cause albinism?
lack of migration of neural crest cells to skin (form melanocytes)
What event in embryology can cause albinism?
lack of migration of neural crest cells to skin (form melanocytes)
What genetic error can cause Severe Combined Immnuodeficiency (SCID)?
Adenosine deaminase deficiency
what group of people can be seen with pyruvate dehydrognease deficiency
alcoholics due to B1 deficiency
What is a complication of cystinuria?
cystine kidney stones
What is a dominant negative mutation?
a mutation that exerts a dominant effect because the body cannot produce enough of the normal gene product with only one allele functioning normally
What is a good mnuemonic for the four glycogen storage diseases?
Very-Von Gierke's Poor-Pompes Carbohydrate-Cori'sMetabolism-McArdles
What is commonly associated with xeroderma pigementosa?
dry skin, melanoma and other cancers
What is crucial to the diagnosis of an Autosomal dominant disease?
Family history
What is genetic anticipation?
the severity of the disease worsens or age of onset of disease is earlier in succeeding generations
What is inheritance of G6PD deficiency and what population is effected more often?
X-linked recessive; blacks
What is NAD/NADP made from?
Niacin, Serotonin, melatonin
What is osteogenesis imperfecta often confused with?
child abuse
What is the biochemical defect in Metachromatic leukodystrophy and what is the inheritance pattern?
deficiency of arylsulfatase A;Autosomal recessive
What is the biochemical defect in Nieman-Pick disease and how is it inherited
deficiency of Betaglucocerebrosidase;autosomal recessive
What is the biochemical effect of G6PD deficiency?
decrease in NADPH which is necessary to reduce glutathione which in turn detoxifies free radicals and peroxides
What is the cause of Cystinuria and what are the signs/symptoms?
inheritied defect o the tubular amino acid transporter for Cystine, ornithine, Lysine and Arginine in kidneys excess cystine in urine
What is the cause of Fabry's disease and what is the common clinical problem
Alpha-galactosidase A deficiency; gives accumulation of ceramide trihexoside causing renal failure
What is the cause of Fabry's disease and what is the common clinical problem
Alpha-galactosidase A deficiency; gives accumulation of ceramide trihexoside causing renal failure
What is the cause of galactosemia?
Absence of galactose-1-phosphate uridyltransferase; accumualtion of toxic substances (galactitol)
What is the cause of Fabry's disease and what is the common clinical problem
Alpha-galactosidase A deficiency; gives accumulation of ceramide trihexoside causing renal failure
What is the characteristic defect in Hurler's syndrome?
Alpha-L-iduronidase deficiency leads to corneal clouding and mental retardation
What is the characteristic findings in Neurofibromatosis?
Multiple café-au-lait spots, neurofibromas, increased tumor susceptibilty
What is the clinical picture of a patient with cystic fibrosis?
pulmonary infections, exocrine pancreatic insufficiency, infertility in men
What is the clinical picture of Duchenne's muscular dystrophy?
muscular weakness and degeneration
What is the defect in Maple Syrup Urine disease?
decreased Alpha-ketoacid dehydrogenase. blocks degradation of branched amino acids; Ile. Val. Leu
What is the epidemiology of lactose intolerance?
Age-dependent and/or hereditary (blacks and Asians)
What is the etiology of Homocystinuria?
defect in cystathionine synthase. Two forms: 1. deficiency 2. decreased affinity of synthase for pyridoxal phosphate (cofactor)
What is the finding of Hunter's syndrome on H&P
mild mental retardation but no corneal clouding
What is the formula for Hardy-Weinberg equilibrium?
p^2 +2pq + q^2 =1 and p+q=1
What is the genetic mech. of Cystic fibrosis and it's inheritance?
AR; multiple loss-of-function mutations in a chloride channel
What is the genetic mechanism of Duchenne's muscular dystrophy?
X-linked recessive; caused by multiple loss-of-function mutations in a muscle protein
What is the genetic mechanism of Fragile X MR?
X-linked; progressive expansion of unstable DNA causes failure to express gene-encoding RNA-binding protein
what is the genetic mechanism of Neurofibromatosis
AD, multiple loss-of function mutations in a signaling molecule
What is the genetic problem in Down's Syndrome?
trisomy 21 chromosomal imbalance
What is the inheritance of Krabbe's disease?
Autosomal recessive
what is the inheritance pattern and carrier frequency in Tay-Sach's?
Autosomal recessive; 1:30 inJews of European descent and 1:300 in the general populaition
What is the inheritance pattern of Ehlers-Danlos syndrome?
10 types of this syndrome:Type IV; Auto Dominant Type VI; Auto Recessive Type IX; X-linked recessive
What is the inheritance pattern of Gaucher's disease?
Autosomal recessive
What is the inheritance pattern of xeroderma pigmentosa?
autosomal recessive
What is the inheritiance pattern of Fabry's disease?
X-linked recessive
What is the lab symptoms of G6PD deficiency?
Heinz Bodies: altered hemoglobin precipitate in RBC
What is the most distinguishing finding in Tay-Sach's disease on Physical exam
cherry red Macula; these patients die by 3
What is the pathogneumonic cell type founde in Gaucher's disease?
Gaucher's cells with the characteristic 'crinkled paper' appearance of enlarged cytoplasm
What is the pattern of inheritance of Leber's hereditary optic neuropathy?
mitochondrial inheritance
What is the phenotype in Osteogenesis imperfecta?
increased susceptibility to fractures; connective tissue fragility
What is the phenotype of Down's syndrome?
Mental and growth retardation, dysmorphic features, internal organ anomalies especially heart problems
What is the phenotype of Fragile X?
mental retardation, characteristic facial features, large testes
What is the predominant problem in Ehlers-Danlos syndrome?
Faulty collagen synthesis
What is the prevalance of cystic fibrosis?
1:2000 whites; very rare among Asians
What is the prevalance of Neurofibromatosis?
1:3000 with 50% being new mutations
What is the prevalence of Down's syndrome and what are the risk factors?
1:800; increased risk with advanced maternal age
What is the prevalence of Duchenne's musc. dys.
1:300; 33% new mutations
What is the prevalence of Fragile X- associated mental retardation?
1:1500 males: can be in females, is a multi-step process
What is the prevalence of osteogenesis imperfecta?
1:10,000
What is the prevalence of Phenylketonuria?
1:10,000
What is the priamry defect in Fructose intolerance and how is it inherited?
defiency of aldolase B,autosomal recessive
What is the primary defect in Alkaptonuria?
congenital defiency of homogentisic acid oxidase in the degradative pathway of tyrosine
What is the primary defect(s) found in Phenylketoneuria?
either 1.decreased phenylalanine hydroxylase or2. decreased tetrahydrobiopterin cofactor
What is the rate-limiting enzyme in the Hexose- Monophosphate shunt?
Glucose-6-phosphate dehydrogenase
What is the result of pyruvate dehydrognease deficiency?
backup of substrate (pyruvate and alanine) resulting in lactic acidosis
What is the specific defect in Xeroderma pigmentosa?
defective excision repair such as uvr ABC exonuclease; have inability to repair thymidine dimer formed by UV light
What is the treament of Cystinuria and what is a possible consequence of not treating?
Acetazolide to alkalinize the urine cystine kidney stones due to excess cysteine
What is the treatment of fructose intolerance?
decrease intake of both fructose and sucrose (glucose + fructose)
What is the treatment of Homocystinuria?
1. For a defiency in cystathionine synthase tx by decrease Met and increase Cys in diet 2. for decreased affinity of synthase Tx by decrease vitamin B6 in diet
What is the Tx of galactosemia?
Exclude galactose and lactose (galactose + glucose) from diet
what offspring of females affected with a mitochondrial inherited disease will be effected?
all offspring can be effected
what percent of offspringfrom two autosomal recessivecarrier parents will beeffected?
25%
what percent of sons of aheterazygous mother carryingan x-linked disease will beeffected?
50%
What period of life doautosomal dominant defectspresent in?
often present clinically afterpuberty
What three phenyl ketonesbuild up in the urine of PKUpatients?
phenyl-acetate, phenyl-lactate,phenyl-pyruvate
What to thyroxine and Dopahave in common
both derived form tyrosine
What type of genetic error isusually more severeautosomal recessive ordominant?
AR disorders are often moresevere
AR disorders are often moresevere
mitochondrial
When do patients usuallypresent with autosomalrecessive disorders?
present in childhood
Why are RBC so susceptible toGlycolytic enzyme def.
RBC's metabolize glucoseanaerobically (nomitochondria) and dependson glycolysis
Why do people with fructoseintolerance becomehypoglycemic?
deficent aldolase B causes the accumulation of Fructose 1- phosphate which acts as a phosphate sink and traps the phosphate. Decreased phosphate availability inhibits glycogenolysis andgluconeogenesis
X-linked recessive disease isaften more severe in
males
1,3-BPG to 2,3-BPG via..
bisphosphoglycerate mutase
Acyl
coenzyme A, lipoamide
aldehydes
TPP
Arachidonate
prostaglandins, thromboxanes, leukotrienes
Associate the following signalmolecule precursors.
j
At body pH, what AA arenegatively charged?
Arg and Lys (His is neutral at pH 7.4)
At body pH, what AA arepositvely charged?
Asp and Glu
ATP to cAMP via
adenylate cyclase
By what rxn order kineticsdoes alcohol dehydrogenaseoperate?
zero order kinetics
CH(3) groups
SAM
Choline
CDP-choline
CholineACh via
cholineacetyltransferase
CO(2)
biotin
Contrast glucagon andinsulin.
glucagon phosphorylates stuff; -turns glycogen synthase off andphosphorylase on
Contrast hexokinase andglucokinase.
hexokinase throughout thebody, -GK in liver and haslower affinity but highercapacity for glucose
Contrast hexokinase andglucokinase.
only HK is feedback inhibitedby G6P
Does insulin affect glucoseuptake of brain, RBC's andliver?
No
Does insulin inhibit glucagonrelease by alpha cells ofpancreas?
yes
electrons
NADH, NADPH, FADH(2)
Fructose-6-phosphate
fructose-1,6-bis-P via PFK(rate limiting step of glycolysis)
Glucose
Glucose UDP-Glucose
glutamate to GABA via
glutamate decarboxylase (requires vit. B6)
GTP to cGMP via
guanylate cyclase
How are ketone bodiesexcreted?
in urine
How are ketone bodiesformed?
FA and AA converted toacetoacetate and B-hydroxybutyrate
How do the statin drugswork?
they inhibit HMG-CoAreductase
How does disulfiram work?
inhibits acetylaldehyde dehydrogenase
How does FA enter thecytosol?
via citrate shuttle
How does FA enter themitochondria?
via the carnitine shuttle
How does lead affect hemesynthesis?
inhibits ALA dehydratase andferrochelatase prevents incorporation of Fe
How does the brainmetabolize ketone bodies?
to 2 molecules of acetyl coA
How is bilirubin removedfrom the body?
collected by liver, conjugated with glucuronate, excreted in bile
How is ethanol metabolized?
ethanol oxidized to acetylaldehyde by alcohol dehyd and NAD+acetalaldehyde ox to acetate by acetylaldehyde and NAD+
How is FA entering themitochondria inhibited?
by cytoplasmic malonyl-CoA
How is glutamate convertedto a-ketogluturate
By the loss of amonium andreduction of NADP
How is glutamine convertedto glutamate?
By the loss of amonium
How is heme catabolized?
scavenged from RBC's and Fe+2 is reused
How is LDL uptakeundergone?
by target cells throughreceptor-mediatedendocytosis
How is most plasmacholesterol esterfied?
LCAT(lecethin-cholesterol acyltransferase)
How is NAD+ generally usedmetabolically?
catabolic processes
How is NADPH generally usedmetabolically?
anabolic processes (steroid and FA synthesis), respiratory burst, P-450
How is TCA regulated?
by need for ATP and supply ofNAD+
How many ATP's per acetylCoA?
12
How many ATP equivalantsare needed to generateglucose from pyruvate?
6
How many enzyme activitiesdoes pyruvate dehydrognasepossess
3
How many moles of ATP aregenerated aerobically throughG3P shuttle?
36
How many moles of ATP aregenerated aerobically throughmalate shuttle?
38
How many moles of ATP aregenerated anaerobically?
2
In what tissue does hemesynthesis occur (2)?
liver and bone marrow
Insulin mneumonic
insulin moves glucose intocells
Is Serum C peptide presentwith exogenous insulinintake?
No
Kwashikor results from aprotein deficient MEAL(mneumonic)
Malabsorption, Edema,Anemia, Liver (fatty)
Mnemonic forgluconeogenesis irreversibleenzymes?
Pathway Produces FreshGlucose
Mnemonic for SAM.
SAM the methyl donor man
Name 6 common products ofpyruvate metabolism?
glucose, lactate, Acetyl CoA, CO2, OAA, Alanine
Name the activated carrierswith associated moleclues(one carbon units).
tetrahydrofolates
phosphoryl
ATP
Uncouplers stop ATPproduction? T/F.
False
Underproduction of hemecauses what anemia?
microcytic hypochromic anemia
What AA are required duringperiods of growth?
Arg and His
What are clincial syndromesof this disorder?
xanthomas, atherosclerosishomozygotes = MI by age 30
What are major pathwaysoccur in the liver (8)?
most includinggluconeogenesis, etc.
What are the activators ofglycgenolysis?
cAMP, and calcium ion (Sk.Ms.)
What are the cofactors ofpyruvate dehydrogenase (5)?
pyrophosphate, lipoic acid,CoA, FAD and NAD
What are the components of acholymicron remnant?
TG, FFA and apo E
What are the components of acholymicron?
TG, apo C-II, apo E, B-48, apo A
What are the components ofIDL?
less TG, CE, B-100 and E
What are the components ofLDL?
CE and B-100
What are the components ofVLDL?
TG, Cholesterol ester, B-100,CII and E
What are the degradationproduct steps (3)?
heme to biliverdin to bilirubin
What are the effectorhormones of cholesterolsynthesis?
insulin increases, glucagondecreases
What are the effectorhormones of glyc and pyr ox?
decreased glucagon andincreased insulin
What are the effectorhormones of glycogenolysis?
insulin decreases, epi andglucagon increases
What are the effectorhormones of lipogenesis (2)?
insulin increases, glucagondecreases
What are the electrontransport chain inhibitors?
rotenone, antimycin A, CN-, CO
What are the essentialglucogenic/ketogenic AA?
Ile, Phe, Try
What are the essentialgluconeogenic AA?
Met, Thr, Val, Arg, His
What are the essentialketogenic AA?
Leu and Lys
What are the irreversibleenzymes of gluconeogenesis(4)?
pyruvate carboxylase, PEP carboxykinase,fructose-1,6 bisphosphotase, glu-6-phosphotase
What are the irreversibleenzymes of glycolysis (4)?
glucokinase/hexokinase,PFK,pyruvate kinase,pyruvate dehdrogenase
What are the main substratesused by adipose tissue (2)?
-glucose, -lipoproteintriacylglycerol
What are the main substratesused by brain?
-glucose, -aa and ketonebodies when starved, -polyunsat FA in neonates
What are the main substratesused by heart?
FFA, -some glucose, -lactate,-ketone bodies, VLDL andcholymicrom triacylglycerol
What are the main substratesused by liver?
FFA, -glucose, -lactate, -glycerol, fructose, -AA
What are the major activatorsof gluconeogenesis?
Acetyl CoA for pyruvatecarboxylase and cAMP for PEPcarboxykinase and F-1,6-bis-P
What are the major activatorsof glycolysis and pyruvateoxidation?
AMP, fructose2,6-bis-P,fructose 1,6-bis-P in muscle,CoA, NAD, ADP and pyruvate
What are the major metabolicpathways of the adiposetissue (2)?
- esterfication of FA's -lipolysis
What are the major metabolicpathways of the brain (2)?
-glycolysis,-aa metabolism
What are the major metabolicpathways of the heart?
Aerobic pathways like Boxidation and TCA cycle
What are the major productsof the adipose tissue (2)?
-FFA, -glycerol
What are the major productsof the brain?
lactate
What are the major productsof the liver (10)?
glucose,-VLDL,-HDL,-ketonebodies,-urea,-uric acid, -bileacids, -plasma proteins
What are the major regulatoryenzymes of gluconeogenesis(3)?
pyruvate carboxylase, PEPcarboxykinase and F-1,6-bis-P
What are the major regulatoryenzymes of glycolysis andpyruvate oxidation?
PFK and pyruvatedehydrogenase
What are the major regulatoryenzymes of cholesterolsynthesis?
HMG-CoA reductase
What are the products of theliver in the fasting state?
glucose and ketone bodies
What are the products of theliver in the fed state?
glycogen and fats/VLDL
What are the products of theTCA cycle?
3NADH, 1FADH2, 2CO2,1GTP per Acetyl CoA
What are the some causes ofhyperbilirubinemia (4)?
massive hemolysis, -block incatabolism, -displaced frombinding sites on albumin,decreased excretion
What are the sources ofhyperbilirubinemia (2)?
conjugated (direct/glucuronidated) andunconjugated(indirect/insoluble)
What are the specialistenzymes of muscle (2)?
-lipoprotein lipase, and welldeveloped resp chain
What are the specialistenzymes of the adiposetissue (2)?
-lipoprotein lipase,-hormonesensitive lipase
What are the specialistenzymes of the heart (2)?
-lipoprotein lipase, -respiratory chain welldeveloped
What are the specialistenzymes of the liver?
-glucokinase,-glu-6-phosphotase,-glycerolkinase, -PEP carboxykinase, -fructokinase,-arginase,-HMGcoA synthase and lyase, -7ahydroxylase
What are the three sites in theelectron transport chain foractive proton transfer?
NADH dehydrogenase, Cyt b/c1, and cytochrome oxidase aa3
What can occur as an excessof cholymicrons (3)?
pancreatitis, lipemia retinalisand eruptive xanthomas
What can occur as an excessof VLDL?
pancreatitis
What catalyzes cholymicronto cholymicron remnant?
lipoprotein lipase
What catalyzes IDL to LDL?
hepatic TG lipase
What catalyzes VLDL to IDL?
lipoprotein lipase
What causes a hangover?
acetylaldehyde accumulates
What color is bilirubin andwhat is the condition ofexcess?
yellow, jaundice
What complex is pyruvatedehydrogenase similar to?
a-ketogluturatedehydrogenase complex
What do LT c4, D4 and E4 do(4)?
bronchconstriction,vasoconstriction, contractsmooth muscle, increasevascular permeability
What does breath smell likeduring ketoacidosis?
fruity (acetone)
What does excess LDL cause(3)?
atherosclerosis, xanthomas,and arcus corneae
What does oligomycin do toETC?
ATPase inhibitor thatincreases proton gradient butnot ATP production
What does PGI stand for?
platelet gathering inhibitor
What does the COX pathwayyield?
thromboxanes,prostaglandins andprostacyclin
What does the lipooxygenasepathway yield?
leukotrienes
What does this stand for?
Ornithine, citrulline,carbamoyl-p, aspartate,arginosuccinate, fumurate,arginine, urea
What enzyme catalyzes therate limiting step ofcholesterol syn.?
HMG-CoA reductase
What induces the PPP?
insulin
What is a major component ofatherosclerotic plaque?
modified LDL
What is an uncoupling agentto the ETC?
2,4 DNP (dynamite)
What is cofactor required formethionine (SAM)regeneration?
vit B12
What is does PGI 2 inhibit (2)?
platelet aggregation andvasodilation
What is familial hypercholesteremia?
AD genetic defect in LDLreceptor
What is Kwashikor?
protein malnutrition
What is LT B4?
neutrophil chemotactic agent
What is Marasmus?
Protein-calorie malnutritionresulting in tissue wasting
What is the activator oflipogenesis?
Citrate
What is the activator of PPP?
NADP+
What is the clinical picture ofKwashikor?
small child with swollen belly
What is the committed step ofheme synthesis?
glycine + succ CoA to deltaaminolevulinate
What is the composition ofATP?
Base(adenine), ribose, 3phosphoryls
What is the consequence ofaccumulated intermediates ofheme synthesis?
porphyrias
What is the easy way toremember the cofactors ofPDH complex?
First 4 B vitamins + lipoicacid
What is the effector hormonefor glycogenesis?
Glucagon
What is the energy content ofthe 2 phosphoanhydridebonds?
7 kcal/mol each
What is the functiion of HDL(2)?
transfers cholesterol fromperiphery to liver acts as arepository for apoC and apoE
What is the functioin oflipoprotein lipase?
FA uptake to cells fromcholy's and VLDL's
What is the function ofaminolevulinate (ALA)synthase ?
rate limiting step of hemesynthesis converts succinylCoA and glycine to ALA
What is the function ofcholymicrons (2)?
delivers dietary TG toperipheral tissues deliversdietary cholesterol to liver
What is the function ofhormone sensitive lipase?
degradation of stored TG's
What is the function of LDL?
delivers hepatic cholesterol toperipheral tissues
What is the function ofphospholipase A2?
liberates arachidonic acidfrom cell membrane
What is the function of PPP(3)?
-produces ribose-5-P from G6P for nucleotide synthesis,-produces NADPH,-part of HMP shunt
What is the function of SAM?
transfers methyl units to widevariety of receptors
What is the function of theCori Cycle?
transfers excess reducingequivalants from RBC's andmuscle to liver to allowmuscle to functionanaerobically
What is the function of Tx A2(2)?
platelet aggregation andvasoconstriction
What is the function of VLDL?
Delivers hepatic TG toperipheral tisssue
What is the inhibitor oflipogenesis (2)?
long-chain acyl-CoA, -cAMP
What is the inhibitor of PPP?
NADPH
What is the limiting reagentof ethanol metabolism?
NAD+
What is the main substrate offast twitch muscle?
glucose
What is the main substrate ofslow twitch muscle?
ketone bodies, FFA, triacylglycerol
What is the major function offast twitch muscle?
rapid movement
What is the major function ofslow twitch muscle?
sustained movement
What is the major function ofthe a1 receptor?
increase vascular smoothmuscle contraction
What is the major function ofthe a2 receptor (2)?
-decrease sympathetic outflow, -decrease insulinrelease
What is the major function ofthe B1 receptor (5)?
increase HR, -inc. contractility, -inc. renin release,-inc. lipolysis, -inc. aq. Humor formation
What is the major function ofthe B2 receptor (3)?
vasodilation, bronchodilation,inc. glucagon release
What is the major function ofthe D1 receptor?
relax renal vascular smoothmuscle
What is the major function ofthe D2 receptor?
modulate transmitter release,esp. in brain
What is the major function ofthe H1 receptor (4)?
-increase mucous production,-contract bronchioles, -pruritis, -pain
What is the major function ofthe H2 receptor (4)?
increase gastric acid secretion
What is the major function ofthe liver?
service for the other organsand tissues
What is the major function ofthe M1 receptor?
CNS
What is the major function ofthe M2 receptor?
decrease heart rate
What is the major function ofthe M3 receptor?
increase exocrine glandsecretions
What is the major function ofthe V1 receptor?
increase vascular smoothmuscle contraction
What is the major function ofthe V2 receptor?
increase water permeabilityand reabsorption in the renalcollecting tubules
What is the major inhibitor ofglyc and pyr ox?
citrate (FA and ketone bodies)ATP and cAMP, -acetyl CoA,NADH, ATP
What is the major inhibitor ofTCA?
ATP, long-chain acyl-coA
What is the major inhibitor ofcholesterol synthesis (2)?
cholesterol and cAMP
What is the major inhibitor ofglycogenesis?
ADP and AMP and F-2,6-bis-P
What is the major metabolicpathway of fast twitchmuscle?
glycolysis
What is the major metabolicpathway of slow twitchmuscle?
Aerobic pathways like B oxidation and TCA cycle
What is the major product offast twitch muscle?
lactate
What is the major product ofslow twitch muscle?
lactate
What is the major regulatoryenzyme of glycogenolysis?
glycogen synthase
What is the major regulatoryenzyme of lipogenesis?
acetyl CoA carboxylase
What is the major regulatoryenzyme of pentosephosphate pathway (PPP)?
glucose-6-P dehydrogenase
What is the major regulatoryenzyme of TCA?
citrate synthase
What is the mechanism forthe ETC inhibitors?
directly block ETC, causedecreased proton gradient
What is the mechanism forthe ETC uncoupler?
inc. membrane permeability,decreases proton gradientand increases O2 consmption
What is the mechanism ofethanol hypoglycemia?
NADH/NAD increases in livercauses diversion of pyruvateto lactate and OAA to malateinhibits gluconeogenesis andthus leads to hypoglycemia
What is the mnemonic for thevarious substrates of the TCAcycle?
Cindy Is Kinky So SheFornicates More Often
What is the mneumonic foressential AA?
PriVaTe TIM HALL
What is the mneumonic formajor apolipoproteins?
A-1 Activates LCAT B-100Binds to receptor C-II is aCofactor for LPL E mediatesExtra (remnant) uptake
What is the mneumonic forthe Urea cylce substrates?
Ordinarily, Careless CrappersAre Also Frivolous AboutUrination
What is urobilinogen?
an intestinal intermediatereabsorbed to blood andexcreted in urine as urobilin
What other physiological sideaffect occurs by thishypoglycemia?
fatty liver seen in chronicalcoholics
What rxn does pyruvatedehydrogenase catalyze?
pyruvate+NAD+CoA goes toacetyl-CoA +CO2+NADH
What second messengersystem does Gi workthrough?
adenylcyclase reduces cAMP levels and protein kinase A is reduced
What second messengersystem does Gq workthrough?
phospholipase C, PIP2 to IP3 and DAG. DAG works through protein kinase C IP3 increases IC calcium ion
What second messengersystem does Gs workthrough?
adenylcyclase converts ATP tocAMP to phosphorylateprotein kinase A
What some properties ofbilirubin (3)?
sparingly water soluble toxicto CNS transported byalbumin
What step does this enzymework on?
HMG-CoA to mevalonate
What suppressesglycogenesis?
insulin
What tissues require insulinfor glucose uptake?
adipose and skeletal muscle
What type of metabolismoccurs in the both (3)?
-gluconeogenesis, -urea cycle, -heme synthesis
What type of metabolismoccurs in the cytoplasm (5)?
glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER)steroid synthesis (SER)
What type of metabolismoccurs in the mitochondria(3)?
Beta oxidation, Acetyl-CoA production, Kreb's cycle
When are ketone bodiesformed (2)?
during prolonged starvationdiabetic ketoacidosis
Where are basic AA found inhigh amounts?
in Histones that bind tonegative DNA
Where are cholymicronsmade?
small intestine
Where are ketone bodiesmade?
liver
Where does FA degradationoccur?
mitochondria, where it will be used
Where does FA synthesisoccur?
cytosol
Where is ALA synthase foundand what inhibits it?
mitochondria, heme
Where is HDL secreted from(2)?
liver and small intestine
Where is insulin made?
B cells of pancreas
Where is NADPH generated?
is a product of HMP shuntand the malate dehydrogenase rxn
Where is SAM generated?
From ATP and methionine
Where is VLDL made?
liver
Which ketone body isdetected in urine test (1only)?
acetoacetate
Carbon monoxide has agreater affinity for whatmolecule?
CO has 200x greater affinityfor hemoglobin than foroxygen
Describe the subunits forhemoglobin?
hemoglobin is composed of 4polypeptide subunits (2 alphaand 2 beta)
During the cycle of thesodium pump, it is __.
phosphorylated
How are enzymes regulated?
1. enzyme concentration alteration (synthesis and/or destruction) 2. covalent modification (eg. phosphorylation) 3. proteolytic modification (zymogen) 4. allosteric regulation (eg. feedbackinhibition) 5. transcriptional regulation (eg. steroid hormones)
How does calcium causeskeletal muscle contraction?
Ca2+ ; activates troponin ; moves tropomyosin ; exposes actin-bining site ; allows actin/myosin interaction
How does calcium causesmooth muscle contraction?
Ca2+ ; binds to calmodulin because smooth muscle doesn't have troponins!
How does procollagenmolecules become collagenfibrils?
procollagen molecules cleavedat terminal regions bypeptidases to become insolubletropocollagen, which aggregatesto form fibrils procollagenmolecules are exocytosed intoextracellular space, where thisprocess occurs
How is CO2 transported fromtissue to lungs?
- binds to amino acids inglobin chain (at N-terminus),not to heme - favors T form of Hb (thus promotes O2unloading)
How is collagen fibillarstructure reinforced?
by the formation of covalentlysine-hydroxylysinecrosslinks betweentropocollagen molecules
How is hemoglobin structureregulated?
increased Cl-, H+, CO2, DPG,and temperature favor T form(low affinity of O2)--shiftingthe dissociation curve to theright, leading to increased O2unloading
Most cells are in which cellcycle phase?
G0
On what cellular stuctures aremicrotubules found?
flagella, cilia, mitotic spindles
On which cells isphosphotidylcholine (lecithin)a major component?
- RBC membranes - myelin - bile - surfactant (DPPC-dipalmitoyl phosphatidylcholine) - also used in the esterification ofcholesterol
Only the cytoplasmic side ofmembrane contains what?
glycosylated lipids or proteins
The lower the Km, the(higher/lower/remains same)the affinity
higher
What are the 2 forms ofhemoglobin?
- T (taut) form has low affinity for oxygen - R (relaxed) form has 300xhigher affinity for oxygen Hb exertspositive cooperativity and negativeallostery, accounting for thesigmoid-shaped O2 disassociationcurve (which myoglobin doesn't have)[Hint: When you're RELAXED, you doyour job better (carry more O2)]
What are the cell cyclephases?
Mitosis (Prophase- Metaphase-Anaphase-Telophase) G1 (Gap or Growth) S (Synthesis of DNA)G2 (Gap or Growth) G0 (quiescent G1 phase)
What are the characteristicsof a microtubule?
- cylindrical structure 24nm india and variable length - helicalarray of polymerized dimers ofalpha- and beta-tubulin (13 percircumference) - each dimer has2 GTP bound - grows slowly,collapses quickly - involved inslow axoplasmic transport inneurons
What are the characteristicsof competitive inhibitors?
- resemble substrates - bind reversibly to active sites ofenzymes - high substrate concentrations overcomes effect of inhibitors - Vmax remains unchanges - Km increases compared to uninhibited
What are the characteristicsof noncompetitive inhibitors?
- doesn't resemble substrate - bind to enzyme but notnecessarily at active site - inhibition can't be overcome byhigh substrate concentration - Vmax decreases - Km remains unchanged compared touninhibited
What cell cycle phases arevariable in duration?
G1 and G0
What drugs act onmicrotubules?
mebendazole/thiabendazole (antihelmintic)-taxol (anti-breast cancer) - griseofulvin (antifungal) - cholichicine (anti-gout)
What drugs inhibits thesodium pump?
- Ouabain inhibits the pumpby binding to the K+ site -cardiac glycosides (digoxin,digitoxin) also inhibit thepump, causing increasedcardiac contractility
What is methemoglobinemia?
blood disorder wheremethemoglobin, an oxidizedform of hemoglobin (ferric,Fe3+) that does not bind O2as readily. Iron in Hb isnormally in a reduced state(ferrous, Fe2+)
What is the differencebetween collagen fibril andcollagen molecule?
fibril is made of moleculescollagen fibril--manystaggered collagen moleculeslinked by lysyl oxidasecollagen molecule--3collagen alpha chains, usuallyof Gly-x-y (x and y = pro,OH-pro, or OH-lys)
What is the first step informing collagen from prolyland lysyl residues? Wheredoes it occur? What nutrientdoes it require?
hydroxylation endoplasmicreticulum vitamin C
What is the plasmamembrane composition?
- cholesterol (~50%, promotes membrane stability)- phospholipids (~50%) - sphingolipids - glycolipids - proteins
What is the sodium pump?
Na-K ATPase
What molecules, how many ofthem, and in what directionare moved across themembrane by the sodiumpump?
3 Na go out and 2 K go in
Where is the sodium pump?
on the membrane, with theATP site on the cytoplasmicside of the pump
Which cell cycle phase isshorter in rapidly dividingcells?
rapidly dividing cells have ashorter G1 phase
Which cell cycle phase isusually shortest?
mitosis
Arthralgia's, fatigue,headaches, skin changes,sore throat, alopecia aresymptoms foundin whatvitamin deficiency
Vit A (Retinal)
How does sarcoidosis causehypercalcemia?
in sarcoid, epitheliodmacrophages convert vitaminD into it's active form leadingto increased absorption ofcalcium
How many ATP are madefrom Niacin
Niacin=NAD niacin is B3=3 ATP
What are the characteristicfindings seen in Riboflavindeficiencies
Riboflavin is B2 2C's=cheilosis and Cornealvascularization and alsoAngular stomatitis
What are the fat solublevitamins
D,A,K,E
What are the findings in Vit Dexcess?
Hypercalcemia, loss ofappetite, stupor
What are the possible causesof hypercalcemia?
1. Vit D intoxication 2.Malignancy 3.Hyperparathyroidism 4. Milkalkalisyndrome 5.Sarcoidosis 6. Paget's diseaseof bone
What are the signs andsymptoms of vit B12deficiency?
1. Macrocytic megaloblasticanemia 2. Neurologicsymptoms-optic neuropathy,subacute combineddegeneration 3. glossitis
What are the signs of Biotindeficiency and what arepossilble causes?
dermatitis, enteritisantiobiotic use and ingestionof raw eggs
What are the signs of Folatedeficiency?
Macrocytic megaloblasticanemia sprue
What are the symptoms in VitB5 deficiency
dermatitis, enterititis,alopecia, adrenal insufficiency
What are the symptoms ofPellagra
3 D's Diarrhea, Dermatitis,Dementia, and also Beefyglossitis
What are the usual causes ofVit B12 deficiency?
1. Malabsorption- Sprue,enteritis, Diphyllobthriumlatum (Dr. Lohr's fish tapeworm) 2.lack of intrinsic factor (pernicious anemia) 3.Absence of the terminal ileum- Crohn's disease or surgery
What are the water solublevitamins
B complex vitamins(B1,2,3,5,6,12), Vit C, Biotin,Folate
What can induce pyridoxinedeficiency? Symptoms?
INH and oral contraceptivesconvulsion, hyperirritability
What clotting factors are Vit Kdependent and what anticlottingdrug acts as a Vit Kantagonist?
Factors II, VII, IX, X andProtein C and S Warfarin
what disease is characterizedby polyneuritis, cardiacpathology and edema andwhat is the cause
Beriberi (Ber1BerI), due to VitB1 deficiency
What diseases conditions arecaused by Vitamin Ddeficiency?
Rickets in kids Osteomalaciain adults hypocalcemic tetany
What diseases is caused byVit C deficiency and what arethe findings?
Scurvy swollen gums,bruising, anemia, poor woundhealing
What is B12 used for in thebody?
Cofactor for homocysteinemethylation andmethylmalonyl-CoA handling
What is Niacin's function inthe body and from what can itbe derived
part of NAD, NADP and isderived from tryptophan
What is the active form ofVitamin D?
1,25 (OH)2 D3 = active form
What is the alternate name ofVit B3, problems indeficiency, common cause ofdefieciency
niacin Pellagra Hartnupdisease, malignant carcinoidsyndrome, and INH
What is the alternate name ofvitamin B1 and what are thecharacteristic diseases of it'sdeficiency
Beriberi and Wernicke-Korsakoff syndrome
What is the folic acidprecursor in bacteria andwhat antibiotics exploit thisfact?
PABA is the precursor sulfadrugs and dapsone are PABAanalogs
What is the form of vitamin Dconsumed in milk?
D2 = ergocalciferol
What is the form of Vitamin Dfound in sun-exposed skin?
D3 = cholecalciferol
What is the function andalternate name of Vit. B2
cofactor in oxidation andreduction (FAD,FMN)RiboFlavin
What is the function of Biotin?
Cofactor for carboxylations 1. Pyruvate to oxaloacetate 2. Acetyl-CoA to malonyl Co-A3. Prprionyl-CoA to methylmalonyl-CoA
What is the function of folicacid?
coenzyme for 1-carbontransfer;methylation reactionsimportant for the synthesis ofnitrogenous bases in DNAand RNA
What is the function of Vit A,it's alternate name, andsymptoms in deficiency
visual pigments (retinal)retinol night blindness anddry skin
What is the function of Vit B1
it becomes ThiaminePyrophosphate (TPP) and isused in: oxidativedecarboxylation of Alphaketoacids (pyruvate, Alphaketoglutaratecofactor fortranketolase in the HMP shunt
What is the function of Vit B6
B6 (pyridoxine) is convertedto pyridoxal phosphate acofactore in transaminationreactions (ALT & AST),decarboxylation, and transsulfuration
What is the function of Vit E?
antioxidant; especially inErythrocytes where it protectsthem from hemolysis Vit E isfor Erythrocytes
What is the function ofvitamin C?
1. Cross linking of collagen hydroxylation of proline and lysine in collagen synthesis keeping iron in the Fe2+ reduced state making it more absorbable 3. Cofactor for coverting dopamine to norepinephrine
What is the function ofVitamin D?
increase intestinal absorptionof Calcium and phosphate
What is the function ofVitamin K?
catalyzes gammacarboxylationof glutamicacid residues on variousproteins concerned withclotting.
What is the most commonvitamin deficiency in theUnited States?
Foilic Acid
What is the rule of 2's for VitB2
2 F's, 2C's and 2ATP 2F's=FAD&FMN 2 C's =signs of deficiency cheilosisand corneal vascularizationoxidation of FADH2 leads to 2ATP
What is the sotrage form ofVitamin D?
25-OH D3
What is the source of Vit B12and what is B12's other name
found only in animal productscobalamin
What is vit B5's function andalternate name
constituent of CoA, part offatty acid synthase. Cofactorfor acyl transfersPantothenate (Pantothen-A isin Co-A)
What manifestation is specificto wet beriberi?
high output cardiac failure(dilated cardiomyopathy)
What molecule in egg whitebinds up Biotin and causesdeficiency
Avidin
What problems do you see inVit K deficiency?
Neonatal hemorrhage withincreased PT increased aPTT,but normal bleeding time ingeneral, mild vitamin kdeficiency will prolong PT andhave normal PTT severedeficiency will prolong PT andPTT
What scenerios are vit Bdefieciencies often seen in
alcholism and malnutrition
What test is used to detectB12 deficiency
Schilling test
What two general types ofthings will cause fat solublevitamin deficiency
Malabsorption syndromes( cystic fibrosis and sprue)and mineral oil intake
What vitamins morecommonly cause toxicity andwhy
fat soluble vitamins b/c theseaccumulate in fat
What water soluble vitamindoes not wash out easily fromthe body
B12 which is stored in theliver
What will a defieciency in Vit Elead to?
Increased fragility oferythrocytes
Where is B12 synthesized andstored
synthesized only inmicroorganisms storedprimarily in liver
Where is Vit K synthesizedand what is one cause of Vit Kdeficiency?
synthesized by ntestinal floraprolonged broad spectrumantibiotic use can kill off theflora can cause a deficiency
/ 558
Term:
Definition:
Definition:

Leave a Comment ({[ getComments().length ]})

Comments ({[ getComments().length ]})

{[comment.username]}

{[ comment.comment ]}

View All {[ getComments().length ]} Comments
Ask a homework question - tutors are online