Protein turnover and amino acid catabolism Flashcards
What is the proteasome?
Barrel like protein structure–proteins to be degraded are inserted
Protease activity inside
Lids have ATPase activity and can unfold substrates and deliver into barrel
What is a lysosome?
Membrane bound organelle with acid hydrolases inside
Can degrade stuff
How are proteins to be degraded identified?
Tagged with ubiquitin–directs proteins to proteasome
How are short lived proteins degraded?
By ubiquitin proteasomal system (UPS)
What are degrons?
Signals on some short lived proteins that signal for ubiquitination
e.g. N-terminal residues that are basic or bulky hydrophobic residues
or specific peptide sequences
How does ubiquitination work?
Catalyed by 3 sequential enzymes–E1, E2, and E3 ligases
What does E1 ligase do?
Activates ubiquitin
Covalently binding E1 via high energy thioester bond
Only 1 E1 enzyme
What does E2 do?
Covalent bond broken and formed
Dozens of E2 enzymes in body
What does E3 do?
Recognizes degrons and binds to them and E2s
Ubiquitin is transfered from E2 to protein substrate
Ubiquiting becomes covalently attached to ubiquitin forming polyubiquitin chain
What is the autophagy lysosomal system?
Cellular degradation pathway for long lived proteins and damaged organelles
What is chaperone mediated autophagy?
Chaperone proteins bind to target proteins and escort them to the lysosome
What is microautophagy?
Small pieces of cytoplasm are engulfed by lysosome and degraded
What is macroautophagy?
Large pieces of cytoplasm and organelles become surrounded by a double membrane–isolation membrane–
fuse with a lysosome and degraded.
What is a glucogenic amino acid?
Degraded to pyruvate or citric acid cycle intermediates–can be used for gluconeogenesis
What is a ketogenic amino acid?
Degraded to acetyl-CoA or acetoacetyl-CoA–can be converted to fatty acids or ketone bodies
How does deamination work?
Transamination or oxidative deamination
Excess AAs usually results in synthesis of urea–in liver
How is nitrogen transported to liver from muscle?
Amino acid converted to alanine
Alanine transported in blood to liver
How is nitrogen transported to liver from non-muscle tissues?
Catalyzed by glutamate dehydrogenase–reverse of the nitrogen fixing reaction that occurs in prokaryotes
Glutamine
How is urea synthesized in liver?
Alanine from muscle is converted to glutamate
Glutamine is converted to glutamate and NH4+ by glutaminase
glutamate is converted to NH4+ and alpha-ketoglutarate by glutamate dehydrogenase
NH4+ used to synthesize urea
Where do the nitrogens in urea come from?
Ammonium and aspartate
How is urea formed?
Carbamoyl phosphate formed in mitochondria by carbamoyl phosphate I
Reacts with ornithine to produce citrulline–enters cytoplasm
Aspartate reacts with citrulline
Cleaved to form fumarate and arginine
Arginase cleaves arginine to form ornithine and urea
What is hyperammonemia?
Potentially fatal–high blood levels of NH4+
How is urea cycle regulated?
Carbamoyl phosphate synthetase I is allosterically activated when glutamate and arginine levels are high
What is the relationship between CAC and urea cycle?
Oxaloacetate can be converted to aspartate which can be used in urea cycle
Fumarate produced in urea cycle enters CAC
What is PKU?
Phenylketonuria–accumulate phenylalanine and block AA transport
Brain damage due to low protein and neurotransmitters
How does albinism happen?
Deficit in enzymes that convert tyrosine to melanin
What is alkpatonuria?
Deficit in enzyme that converts tyrosine to acetoacetate–intermediate accumulates
blackens urine, arthritis risk, alters skin pigmentation
What is maple syrup urine disease?
Defect in enzyme that degrades keto acids to propionyl-CoA
accumulates keto-acids
vomiting, convulsions, brain damage
control by limiting branched chain AA consumption
