Amino Acid and Protein Metabolism

Question 1

negative nitrogen balance

Answer 1

not enough protein intake results in need to hydrolyze proteins for energy, leading to large amounts of purines and heme being made and therefore large amounts of nitrogen, which is excreted as urine

Question 2

what is an essential amino acid

Answer 2

an amino acid that we cannot synthesize in our body and therefore need to consume

Question 3

list the essential amino acids

Answer 3

isoleucine
leucine
lysine
methionine
phenylalanine
threonine
tryptophan
valine
histidine
*arginine, cysteine, and tyrosine are only essential if their precursors are unavailable

Question 4

how are essential amino acids obtained

Answer 4

through the diet

Question 5

how do amino acids get into the cells for utilization

Answer 5

sodium-amino acid cotransporters

Question 6

enteropeptidase

Answer 6

activates several of the enzymes required for protein breakdown (trypsinogen -> trypsin; pancreatic enzymes)
-mutation of enteropeptidase will result in inability to breakdown proteins into amino acids

Question 7

autophagy and protein breakdown

Answer 7

autophagosome fuses with the lysosome and causes degradation of proteins; functions include:
1. replenish nutrient pools
2. nutrients/ATP for starved and stressed cells
3. removal of damaged organelles/dead cells/misfolded proteins

Question 8

ubiquitin-proteosome system

Answer 8

1) proteins are marked for degradation by ubiquitination
-E1 (UB activating enzyme) requires ATP to activate
-E2 (UB conjugating enzyme) conjugates ubiquitin to E2
-E3 (UB ligase complex) transfers ubiquitin from E2 to the target protein
2) receptors on the proteosome bind the ubiquitinated protein
3) the protein-UB complex is degraded by the proteosome

Question 9

4 ways that proteins can be broken down

Answer 9

1) cathepsins in lysosomes
2) calpains (free proteases in cytosol)
3) autophagy
4) ubiquitin-proteosome complex

Question 10

how does HPV virus use the ubiquitin pathway to promote cancer

Answer 10

HPV virus creates E6 protein, which binds to p53 (tumor suppressor gene) and effectively targets it for degradation by the ubiquitin proteosome system

Question 11

transamination of an amino acid in amino acid catabolism

Answer 11

*substrates = amino acid and a-ketoglutarate
*products = a-keto acid and glutamate and ammonia
*cofactor = pyridoxal-5-phasphate (PLP), the active form of vitamin B6
*glutamate becomes an amino donor for non-essential amino acid synthesis

Question 12

what is the a-keto acid produced by transamination used for

Answer 12

1. energy yielding rxns in TCA cycle
2. ketone body synthesis
3. gluconeogenesis

Question 13

how are glutamate and glutamine important for regulation of ammonia levels

Answer 13

1) in the tissues, ammonia gets attached to glutamate (by glutamine synthetase) to form glutamine
2) glutamine is shuttled to the liver and converted back to glutamate (by glutaminase)
3) the free ammonia is excreted by the urea cycle; the glutamate is converted to a-ketoglutarate and used in the TCA cycle

Question 14

how does amino acid catabolism create ATP?

Answer 14

carbon skeletons of amino acids (especially alanine in muscle tissue) gets converted to TCA cycle intermediates and pyruvate, and the TCA cycle yields NADH and FADH2 to be used in the ETC

Question 15

how do amino acids get converted to glucose

Answer 15

all amino acids EXCEPT LEUCINE AND LYSINE can get converted to TCA cycle intermediates and eventually to oxaloacetate, which can be used in gluconeogenesis to form glucose

Question 16

which amino acids can be used to make ketone bodies

Answer 16

phenylalanine
tyrosine
isoleucine
threonine
tryptophan
leucine
lysine

Question 17

how do we convert amino acids to ketone bodies

Answer 17

the ketogenic amino acids are converted to acetyl-CoA, which can form the ketone bodies (beta-hydroxybutyrate and acetoacetate) which can be transported to tissues and enter the TCA cycle to be used for energy
*RATE-LIMITING ENZYME = HMG CoA Synthase

Question 18

which amino acids are ONLY ketogenic (cannot make glucose)

Answer 18

leucine
lysine

Question 19

maple syrup urine disease - causes

Answer 19

blocked degradation of BRANCHED amino acids (isoleucine, leucine, valine) due to decreased branched-chain alpha-ketoacid dehydrogenase, leading to low blood pH

Question 20

maple syrup urine disease - presentation

Answer 20

urine smells like maple syrup/burnt sugar; causes CNS defects, intellectual disability, vomiting, poor feeding

Question 21

mnemonic for maple syrup urine disease

Answer 21

I Love Vermont maple syrup from maple trees (with B1ranches)
= Isoleucine, Leucine, Valine

Question 22

branched-chain alpha-ketoacid dehydrogenase

Answer 22

converts the branched chain amino acids to ketones and succinyl-CoA; deficiency leads to maple syrup urine disease

Question 23

functions of the urea cycle

Answer 23

*prevent ammonia toxicity by converting ammonia to urea in the liver
*biosynthesis of arginine

Question 24

major pathophysiologic cause of hyperammonemia

Answer 24

mutation in ornithine transcarbamylase (an important enzyme in the urea cycle)
-leads to elevated ammonia and glutamine levels
-arginine becomes an essential amino acid (b/c we are no longer synthesizing it)

Question 25

what enzymes use heme as a prosthetic group

Answer 25

oxygen-bearing proteins, including:
-myoglobin
-hemoglobin
-catalase
-cytochromes
*cytochrome P450
-prostaglandin endoperoxide synthase
-guanylyl cyclase

Question 26

what is the rate-limiting enzyme for heme biosynthesis

Answer 26

aminolevulinic acid synthase

Question 27

how is aminolevulinic acid synthase regulated

Answer 27

*inhibited by glucose and hemin
*low levels of heme increases activity of ALA synthase
*high levels of heme decreases activity of ALA synthase

Question 28

locations of the steps of heme biosynthesis

Answer 28

1) rate-limiting step (ALA synthase) occurs in the mitochondria
2) intermediate steps occur in the cytosol and ultimately produce protoporphyrin
3) protoporphyrin goes to the liver, and in the mitochondria, Fe2+ gets added to make heme

Question 29

porphyria

Answer 29

results from a disturbance in heme biosynthesis, leading to overproduction and accumulation of heme

Question 30

characteristics of acute intermittent porphyria

Answer 30

*severe abdominal pain
*tachycardia
*anxiety
*depression
*generalized pain
**port wine color urine
*no cutaneous photosensitivity

Question 31

what enzyme defect causes acute intermittent porphyria

Answer 31

insufficient activity of porphobilinogen deaminase

Question 32

mechanism of acute intermittent porphyria in P450 activity

Answer 32

1) P450 requires heme in order to activate drugs in our body, lowering the amount of free heme
2) ALA synthase is activated by low levels of heme and begins working, producing its intermediaries and ultimately porphobilinogen
3) the defective porphobilinogen deaminase causes buildup of porphobilinogen and ultimately buildup of ALA

Question 33

kernicterus

Answer 33

severe unconjugated hyperbilirubinemia

Question 34

Crigler-Najjar syndrome

Answer 34

a heritable form of hyperbilirubinemia caused by a mutation of the gene encoding UDP-glucoronyltransferase
-loss of its activity results in the inability to attach glucuronic acid to bilirubin (unable to conjugate it) to make it water soluble, so unconjugated bilirubin builds up in the blood