Amino Acid and Protein Metabolism Flashcards
negative nitrogen balance
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
what is an essential amino acid
an amino acid that we cannot synthesize in our body and therefore need to consume
list the essential amino acids
isoleucine
leucine
lysine
methionine
phenylalanine
threonine
tryptophan
valine
histidine
*arginine, cysteine, and tyrosine are only essential if their precursors are unavailable
how are essential amino acids obtained
through the diet
how do amino acids get into the cells for utilization
sodium-amino acid cotransporters
enteropeptidase
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
autophagy and protein breakdown
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
ubiquitin-proteosome system
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
4 ways that proteins can be broken down
1) cathepsins in lysosomes
2) calpains (free proteases in cytosol)
3) autophagy
4) ubiquitin-proteosome complex
how does HPV virus use the ubiquitin pathway to promote cancer
HPV virus creates E6 protein, which binds to p53 (tumor suppressor gene) and effectively targets it for degradation by the ubiquitin proteosome system
transamination of an amino acid in amino acid catabolism
*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
what is the a-keto acid produced by transamination used for
- energy yielding rxns in TCA cycle
- ketone body synthesis
- gluconeogenesis
how are glutamate and glutamine important for regulation of ammonia levels
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
how does amino acid catabolism create ATP?
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
how do amino acids get converted to glucose
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
which amino acids can be used to make ketone bodies
phenylalanine
tyrosine
isoleucine
threonine
tryptophan
leucine
lysine
how do we convert amino acids to ketone bodies
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
which amino acids are ONLY ketogenic (cannot make glucose)
leucine
lysine
maple syrup urine disease - causes
*blocked degradation of BRANCHED amino acids (isoleucine, leucine, valine) due to decreased branched-chain alpha-ketoacid dehydrogenase (B1), leading to low blood pH
*causes increased alpha-ketoacids in the blood, especially those of leucine
I Love Vermont maple syrup from maple trees (with B1ranches)
-amino acids = I, L, V (isoleucine, leucine, valine)
-B1
-branched chain amino acids
-maple syrup urine disease
maple syrup urine disease - presentation
*urine smells like maple syrup/burnt sugar
*vomiting
*poor feeding
*progressive neurological decline / intellectual disability
mnemonic for maple syrup urine disease
I Love Vermont maple syrup from maple trees (with B1ranches)
-amino acids = I, L, V (isoleucine, leucine, valine)
-B1
-branched chain amino acids
-maple syrup urine disease
branched-chain alpha-ketoacid dehydrogenase
converts the branched chain amino acids to ketones and succinyl-CoA; deficiency leads to maple syrup urine disease
functions of the urea cycle
*prevent ammonia toxicity by converting ammonia to urea in the liver
*biosynthesis of arginine
major pathophysiologic cause of hyperammonemia
*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)
what enzymes use heme as a prosthetic group
oxygen-bearing proteins, including:
-myoglobin
-hemoglobin
-catalase
-cytochromes
*cytochrome P450
-prostaglandin endoperoxide synthase
-guanylyl cyclase
what is the rate-limiting enzyme for heme biosynthesis
aminolevulinic acid synthase
how is aminolevulinic acid synthase regulated
*inhibited by glucose and hemin
*low levels of heme increases activity of ALA synthase
*high levels of heme decreases activity of ALA synthase
locations of the steps of heme biosynthesis
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
porphyria - overview
results from a disturbance in heme biosynthesis, leading to overproduction and accumulation of heme
characteristics of acute intermittent porphyria
*severe abdominal pain
*tachycardia
*anxiety
*depression
*generalized pain
port wine color urine
*no cutaneous photosensitivity
what enzyme defect causes acute intermittent porphyria
insufficient activity of porphobilinogen deaminase
mechanism of acute intermittent porphyria in P450 activity
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
kernicterus
severe unconjugated hyperbilirubinemia
Crigler-Najjar syndrome
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
*findings: jaundice, kernicterus (unconjugated bilirubin deposition in brain), elevated unconjugated bilirubin
