Metabolism of alpha amino group of amino acids and urea cycle- Lecture 74 Flashcards
Excess amino acids are metabolized to ______.
pyruvate, TCA cycle intermediates, and acetyl CoA
Most amino acid metabolism occurs in the _____ by the _____ pathway.
liver
urea cycle
Describe the pathway of the breakdown of amino acids via TA reactions that feed into the urea cycle.
amino groups from amino acids are collected as glutamate via transamination in muscle which can be sent to liver where glutamic dehydrogenase converts it to NH3 in a reversible reaction
______ can be broken down by alternative pathways to TA to yield NH3.
serine, histidine, threonine, and cysteine
What is the NH3 yielded from the breakdown of serine, histidine, threonine, or cysteine used for in non-liver tissue?
Glut + NH3 + ATP –> Gln + ADP + Pi
irreversible
Why is the NH3 from the breakdown of serine, histidine, threonine, or cysteine in non-liver tissue used to convert Glut to Gln?
because it needs to get to the liver and NH3 cannot circulate through the blood because it is toxic to the brain
What does a high BUN indicate?
(blood urea nitrate) indicates kidney failure
Where do the steps of the urea cycle occur?
the first two steps occur in the mitochondria
steps 3-5 occur in the cytosol
What is the first reaction of the urea cycle?
HCO3- + NH4+ + 2ATP –> Carbamoyl Phosphate + 2ADP
via carbamoyl phosphate synthase 1 (CSPI)
_____ of urea is made in the first step of the urea cycle.
2/3
____ is a major positive effector of the CSP-1.
Biochemical N-acetyl glutamic acid
What are the final four steps of the urea cycle designed to accomplish?
addition of the alpha amino group of aspartate to CP to form urea
these are difficult and rate limiting
What is the second reaction of the urea cycle?
Ornithine + Carbamoyl –> citrulline + Pi
via ornathine transcarbamolyase (OTC)
citrulline leaves mito
_____ is the most common deficiency in inborn errors of the urea cycle.
OTC
What is the third reaction of the urea cycle?
citrulline + aspartate + ATP –> argininosuccinate + ADP
via argininosuccinate synthase
What is the fourth reaction of the urea cycle?
argininosuccinate –> fumarate + arginine
via argininosuccinate lyase
What is the fifth reaction of the urea cycle?
arginine + H2O –> urea + ornithine
via arginase
ornithine enters mito via same carrier as citrulline in exchange and reenters cycle at reaction 2
How can the urea cycle be linked to the TCA cycle?
fumarate produced in step 4 of the urea cycle can enter the TCA cycle and be converted to malate then OAA
OAA can be converted to aspartate via GOT
What is ammonia toxicity?
deficiency of OTC resulting in inability of NH3 to be converted to urea for excretion
What are the symptoms of ammonia toxicity?
GI tract irritability, nausea, vomiting, lethargy
if more severe, neurological disturbances, mental retardation, seizures, coma, death
Why is NH3 toxic?
interference with blood pH (is basic), depletion of alpha KG out of TCA cycle (via glutamic dehydrogenase reaction), and formation of excess of the excitatory neurotransmitter glutamine (via glutamine synthase reaction)
What treatments are available for NH3 toxicity?
low protein diet
maintain blood pH (acetate buffer)
clean out gut (levulose syrup)
benzoate or phenylacetate (help indirectly remove NH3)
What is the mechanism of action of benzoate for NH3 toxicity?
remove glycine (NH3 –> glycine via glycine synthase)
What is the mechanism of action of phenylacetate for NH3 toxicity?
remove glutamine (NH3 –> Gln via GS)
