SYLLABUS 15: Metabolism of the Alpha Amino Group of Amino Acids and the Urea Cycle Flashcards
what happens to excess aa?
metabolized to pyruvate, TCA cycle intermediates, and acetyl CoA
what happens to alpha amino groups of aa in excess?
all pooled into glutamate by transamination reactions
glutamate releases these amino groups as ammonia
ammonia is converted to urea in liver by urea cycle
where does most aa metabolism occur
muscle and liver
this is where glutamate - aa transamination reacitons occur
what happens in glutamate DH reaction?
where does it occur?
in the liver
takes the alpha amino groups from aa which were collected as glutamate and releases them to ammonia
that is, glutamate is oxidized to aKG + NH3 + NAD(P)H
uses NAD+ or NADP+ as cofactor
this is reversible
indicates that glutamate is a non-essential amino acid b/c can form it from aKG + NH3 + NADH
how does muscle ammonia get metabolized differently than liver ammonia? what reaction takes place?
whereas liver NH3 mixes w/ NH3 from GDH reaction and enters urea cycle, in muscle, must get NH3 to liver to undergo urea cycle, b/c muscle doesn’t have urea cycle
do not want to circulate this NH3 through blood b/c it is toxic to the brain
thus muscle NH3 reacts w/ glutamate to produce glutamine in glutamine synthase reaction
which amino acids undergo the glutamine synthase rxn?
Ser, His, Thr, Cys
what happens to product(s) of the glutamine synthase rxn?
glutamine leaves muscle, circulates to liver
aka glutamine is caryring NH3 produced in muscle to liver
in liver, the enzyme glutaminase hydrolyzes glutamine back to glutamate + NH3, and NH3 -> urea cycle. uses a water to do this.
after a high-protein meal, what is found in the blood? why?
large amounts of glutamate and glutamine
they carry a-amino groups from muscle to liver
what are the reactions of the urea cycle? where does each step occur?
- carbamoyl phosphate synthetase (CPS-I) in MITO
- ornithine transcarbamoylase in MITO
- argininosuccinate synthetase in CYTO
- argininosuccinate lyase in CYTO
- arginase in CYTO
describe the urea cycle
- in the mito, NH3 + CO2 react via CPS-I to form Carbamoyl Phosphate; takes 2ATP -> ADP + Pi
- RATE LIMITING STEP: Carbamoyl Phosphate reacts w/ Ornithine transcarbamoylase to form Citrulline; releases Pi
- Citrulline travels from Mito -> Cyto
In cyto, Citrulline reacts w/ Aspartate, uses an ATP -> ADP + Pi, via Argino Succinate Synthase to make Argino Succinate
- Argino Succinate Lyase acts on intermediate Argino succinate, makes Arginine, releasing Fumarate
- Arginase hydrolyzes Arginine w/ H2O, makes UREA
UREA -> URINE, ORNITHINE is regenerated and enter mito for next round
what is most highly deficient enzyme in urea cycle
ornithine transcarbomylase, rate limiting step of the cycle
is arginine an essential amino acid
only in children, when growing/developing, because cannot make enough Arg from urea cycle for growth/development
in adults, do not need high amounts of Arg, and make enough via urea cycle
what is the structure of urea
where do its parts come from
2 alpha amino groups: 1 from ammonia, 1 from alpha amino group of aspartate
C=O from CO2
how much of urea is made in CPT-1 step fo urea cycle
2/3
what activates CPS-1
NAGA, N-acetylglutamate
it’s formed from glutamate + acetyl CoA, activated by arginine