Week 13 Objectives

Question 1

Describe protein turnover, indicate the mean rate of protein turnover in healthy individuals, and provide examples of human proteins that are degraded at rates greater than the mean rate.

Answer 1

Protein Turnover: most degraded AAs are reused
If not used immediately, AAs are
degraded NOT stored.

Question 2

Outline the events in protein turnover by both ATP-dependent and ATP-independent pathways, and indicate the roles in protein degradation played by the proteasome, ubiquitin, cell surface receptors and lysosomes.

Answer 2

ATP mediated protein degradation: damaged proteins degradation, requiring ubiquitin and ATP

Ubiquitin: attaches signalling target for destruction (changes confirmation)
Proteosome: what gets destroyed

Question 3

• Illustrate the central roles of transaminases (aminotransferases), of glutamate dehydrogenase, glutamine synthetase, and of glutaminase in human nitrogen metabolism.

Answer 3

aminotransferases: transfer of an amino group to make a keto acid.(a-ketoglutarate)

GDH: glutamate + NAD(P) → α-ketoglutarate + NH3 + NAD(P)H (frees ammonia and requires NADPH)

GS: glutamate -> glutamine, fixes ammonia

G: glutamine-> glutamate, frees ammonia into UC

Question 4

Describe the reactions that convert NH3, CO2, and the amide nitrogen of aspartate into urea, and identify the subcellular locations of the enzymes that catalyze urea biosynthesis

Answer 4

Mitochondria: o CO2 + NH4+ combine in the mitochondria to generate carbamoyl phosphate
o Citrullene is shuttled out of the mitochondria
UC: CP, Citrulline, (Aspartate), Arginosuccinate, (Fumarate), Arginine, (Urea), Ornithine

Question 5

Indicate the roles of allosteric regulation and of acetyl-glutamate in the regulation of the earliest steps in urea biosynthesis.

Answer 5

CPS1 requires N-acetylglutamate (NAG) as an allosteric activator
▪ NAGs is synthesized by N-acetylglutamate synthetase
● The enzyme N-acetylglutamate synthetase is activated by arginine

Question 6

Explain why metabolic defects in different enzymes of urea biosynthesis, although distinct at the molecular level, present similar clinical signs and symptoms.

Answer 6

Deficiencies in OTC: increased ammonia, low citrulline and increased orotic acid (orotic aciduria)

Deficiencies in CPS: low everything but CP and ammonia

Deficiencies in arginine/argininosuccinate enzyme: high citrulline and ammonia

Question 7

Movement of Amino acids

Answer 7

Movement of amino acids
● Amino acids move between organs
o Alanine – glucose cycle in muscle
o Alanine and glutamine are the primary amino acids in circulation
▪ Two non-toxic carriers of ammonia