AA metabolism Flashcards
Where do free amino acids come from?
- .Protein turnover
- .Digested food
- .De novo synthesis**
How are amino acids used?
Production of body protein
Synthesis of nitrogen-containing compounds
Degradation
What is hartnup disease? what happens?
Defective transport of nonpolar or neutral amino acids (e.g. Tryptophan) leads to concentrated level in the urine.
protein transporters mediate transport of amino acids in and out of cells, kidney and SI
failure to thrive, nystagmus, tremor, intermittent ataxia and photosensitivity.
Cystinuria?
Defective transport of dimeric cystine and dibasic amino acids Arg, Lys, and ornithine
Formation of cystine crystals in the kidneys (renal calculi)
How are aromatic aa made?
Phe- Tyr
Rib5P- His
How is ala made?
Pyruvate to ala
how is aspartate made?
oxaloacetate to asp to asn
how is glutamate made?
aketo to glutamate
what are Proteolytic enzymes?
degradation of proteins for reabsorption, exo and endo
what does Exopeptidase do?
attacks at C- (carboxypeptidase) or N-terminus
what does Endopeptidase do ?
attacks within the protein at a specific site.
mechanism of action which is dependent on the catalytic enzyme in the active site
what are the 3 intracelluar protein degradation pathways?
Proteasome, lysosome and autophagosome
Lysosomal /Autophagy? what is it
nonselective, active at pH5
What does proteosome do?
large proteasome cytoplasmic complexes that cleave polyubiquinated proteins ubiquitin pathway
how does Extracellular Proteolytic Control work?
enzymes secreted as needed
Secreted as inactive zymogens, activated by proteolytic cleavage
trypsinogen activated by enterokinase
activates chemotrypsinogen
What role do enteropeptidases play in protein digestion?
They are membrane-bound intestinal proteins
They are serine proteases
Convert the zymogen trypsinogen to active trypsin
.Allows trypsin to convert other zymogens to active forms
What are the ketogenic aa?
Leu, Lys
What are the ketogenic and glutogenic aa?
Ile trp, phe, tyr,thr
What does Trp become in TCA cycle?
Pyruvate
What does Lys become in TCA?
acetoacetate
What contributes to GLU in TCA cycle?
Gln, His, Arg
What are the three cycles of how aa are metabolized?
- transaminase
- glutamate dehydrogenase
- urea cycle
what is transamination? what happens?
- Amino group is transferred to an α-ketoacid
- Coupled reactions
- Enzymes called transaminases/aminotransferases
What are the three most important transaminase reactions?
pyruvate + glutamate—- (alanine transferase/ alt)— alanine+ aketo
oxalo +glutamate— (aspartate aminotransferase/ ast)—- asp + aketo
glutamine +h2o—- (glutamine aminohydrolase/GA)—- glutamate + nh3
Transaminases, what do they require?
(PLP)– Derivative of Vitamin B6
What is homocysteinemia?
Met to homocysteine issue , homocysteine methyltransferase nt working , vitamin deficiency
What is homocystinuria?
cystathionine β-synthase not working, met to homocysteine
what are the consequences of homocysteinemia and homocystinuria?
Four organ systems: eye, skeletal, CNS, vascular
What do BCAs metabolize to?
Val and ILe become succincyl CoA
Leu become acetyl CoA
what is maple syrup disease? what happens?
issues with metabolizing BCA
urine give the hallmark maple syrup smell.
accumulate in blood causing toxic effects on brain function and eventually mental retardation
What is Phe metablized into, what enzyme and whats the significance?
Phe to Tyr (phenylalanine hydroxylase)
Phenylketonuria happens here
What is PKU caused by?
defects in the activity of phenylalanine hydroxylase (PAH)
Secondary PKU resulting from tetrahydrobiopterin deficiency
Phe instead converted to phenylpyruvte and then to phenyllactate
What is an important Ser derivative?
Acetylcholine
Important Trp derivatives?
Serotonin, Niacin, needs b6!
Important Tyr derivatives
Dopamine, thyroid, melanin
Important Glu derivatives
Gaba
important arginine derivatives
Arg, Gly,Met
Creatine phosphate, kidney dysfunction means higher blood levels
What is albinism, how does it occur?
Tyrosine to melanin is blocked due to defective tyrosinase
Where do thyroid hormones come from?
Come from Tyr, need iodine (graves disease and stuff)
hyperthyroidism patients treated with iodine, decrease T4 and T3
What are the two ways Nitrogen can be removed?
As ammonia, Glu and Gln in brain, gln and ala in other tissues
As urea
How is NH4 removed from brain?
aKG to GLU to GLN (this process requires ATP and NADPH)
then, Gln becomes Glu again, makes NH4 which goes to urea cycle
How is NH4 removed in muscle?
Glucose becomes pyruvate which is turned into Ala, Ala goes to liver, becomes pyruvate which releases NH4
This NH4 enters urea cycle
In liver, Ala goes to pyruvate via ALT, aKG to Glu via GLDH, NH4 produced
*Alt used to convert pyruvate to Ala
What is the rate limiting step of the urea cycle
NH4 to carbamoyl phophate via carbamoyl synthetase
When is urea produced in urea cycle?
When Arg becomes orthinine via arginase
When can hyperammonemia occur?
NH4—carbamyol phosphate
ornithine—-citrulline
when can citrullemia occur?
citrulline—argininosuccinate (as synthetase)
when can arginosuccinate aciduria occur?
arginosuccinate—arg (arginosuccinate lyase)
what is ammonia toxicity?
NH3 is a toxic agent
pH imbalance ,
Glutamate dehydrogenase catalyzes of glutamate to a-ketoglutarate, a key reactant in the TCA cycle; this inhibits the activity of the TCA cycle
Depletion of glutamate, depletion of neurotransmitter activity
Urea cycle and the high protein diet , correlation?
urea production is increased by a high protein diet and decreased by high carb diet
Provides a source of ammonia nitrogen for gut bacteria, salvage and reuse
Creatine, relevance?
Synthesized from Arg, Gly, Met
Cardioselective isoform of creatine kinase (CK-MB) can serve as a diagnostic for myocardial infarction
non-enzymatically converted from creatine phosphate to creatinine
indicative for kidney dysfunction and muscle degeneration
