Biochem Lecture 30 (Urea)

Question 1

How is glutamate DH reg’d?

Answer 1

1) mass action (rxn is reversible)
2) allosterically: ATP & GTP decrease activity; ADP & GDP increase activity
(i. e. “if energy levels are low in the presence of sufficient amino acids, oxidative deamination of glutamate is stimulated and promotes amino acid catabolism into TCA cycle intermediates.”)

Question 2

What is the overall stoichiometry of urea synthesis?

Answer 2

CO2 +NH4 +3ATP+Aspartate+2H2O —> urea+2ADP+2Pi+AMP+PPi+fumarate

Question 3

Draw the urea cycle (??) At the very least list the enzymes involved.

Answer 3

Question 4

What is the rate limiting step in the urea cycle? What regulates it?

Answer 4

L-Ornithine

—[carbamoyl phosphate synthetase I]—>

L-Citrulline

(Inside mitochondria)

Short-term reg by: directly by [N-acetyl glutamate] which is made when there is an excess of a.a.’s, specifically Arg (i.e. after a protein-rich meal)

Question 5

What is the long-term reuglation of the urea cycle? Under what conditions would it be upregulated?

Answer 5

Long term reg = transcriptional control

—increased in starvation 10-20 fold

Question 6

How do you get the amino groups to the liver to begin with?

Answer 6

There are two routes:

1) Gluatamine Path

First IN PERIPH TISSUE: glutamine synthetase rxn transfers the NH3 to glutamate:

Glutamine Synthetase: glutamate + NH4 + ATP —> glutamine + ADP + Pi

Then IN LIVER glutaminase reverses the rxn in the liver:
Glutaminase: glutamine + H2O glutamate + NH4

2) Glucose-Alanine Pathway (incr w/ starvation)

First IN MUSCLE: NH3 is transferred from A.A. to pyruvate —transam—> alanine —>bloodstream

Then IN LIVER: Alanine + aKG —transam—> glutamate (to urea cycle) + pyruvate (gluconeogenesis back to muscle)

Question 7

Talk to me about inborn errors in urea metabolism

Answer 7

There are congential anomalies assoc’d w/ a defect in each of the five enzymes in the pathway (carbamoyl phosphate synthetase I, arginosuccinate synthase, arginosuccinate lyase, arginase, and ornithine transcarbamoylase)

There is also a 6th assoc’d with N-acetylglutamate synthetase

Question 8

What clinical s/sx would lead you to suspect an inborn error in urea metabolism?

Answer 8

elevated [NH3]plasma