Amino Acid Catabolism

Question 1

What is the major site of amino acid degradation?

Answer 1

the liver

Question 2

what happens to the excess amino acids which aren’t used as building blocks for protein?

Answer 2

they are degraded as amino acids cannot be stored

Question 3

Where are amino acids absorbed into the body?

Answer 3

proteolytic enzymes in stomach and intestine produce single amino acids and di- and tri-peptides
absorbed into intestinal cells and released into blood for absorption by other tissues

Question 4

What are the substances which are toxic in high concentrations which are produced by amino acid breakdown?

Answer 4

ammonia and ammonium

Question 5

What are the major nitrogen-containing excretory muscles?

Answer 5

Urea (made in the liver)
uric acid
creatinine
ammonium ion (NH4+)

Question 6

what are the 3 steps of urea synthesis?

Answer 6

transamination
deamination
urea/ornithine cycle

Question 7

What are the precursors for the urea cycle?

Answer 7

ornithine and carbonyl phosphate

Question 8

What happens in transamination?

Answer 8

aminotransferases move the amino group from alpha-amino acids to alpha-keto acids
usually alpha-ketoglutarate, a TCA intermediate which will give glutamate
transamination occurs in all tissues

Question 9

How is the glutamate produced by transamination transported to the liver?

Answer 9

the amino group of glutamate is transferred to the pyruvate to give alanine or glutamine synthase adds NH4+ to glutamate giving glutamine, these products are major carriers of nitrogen in the blood to liver

Question 10

What happens in deamination?

Answer 10

the amino group of glutamate is converted to free ammonium ion
this happens in the liver

Question 11

What happens in the urea cycle?

Answer 11

one nitrogen from free ammonium, the other from aspartic acid feed into the cycle along with a carbon from CO2 and synthesise urea
the urea cylcle happens in the liver

Question 12

urea cycle

CO2 + NH4+ + 3 ATP + aspartate + 2 H2O to

Answer 12

urea + 2 ADP + 2 Pi + AMP + PPi + fumarate

Question 13

what is the significance of fumarate?

Answer 13

it is generated as an end product of the urea cycle in the cytosol and its conversion to malate enables its carbon to be transported back to the mitochondrial matrix via the malate-aspartate shuttle.

Question 14

How are the carbon skeletons of amino acids degraded after their alpha amino group has been removed?

Answer 14

they are converted to major metabolic intermediates and either converted to glucose or oxidised in the TCA cycle
Ketogenic amino acids
- degraded to acetyl-CoA or acetoacetyl-CoA and can give rise to ketone bodies or fatty acids
Glucogenic amino acids
-degraded to pyruvate or TCA cycle intermediates and can be converted into phosphoenolpyruvate and then into glucose

Question 15

What is alcaptonuria?

Answer 15

an inheited condition where degradation of phenylalanine and tyrosine is blocked

Question 16

What is Maple syrup urine disease?

Answer 16

an inherited disorder where degradation of valine, isoleucine, and leucine is blocked
it causes urine smells like maple syrup and mental and physical retardation
prevented by appropriate diet

Question 17

What is Phenylketonuria?

Answer 17

an inherited disorder where phenylalanine accumulates in all body fluids it leads to severe mental retardation if untreated
therapy: low phenylalanine diet

Question 18

What happens if there is a defect in a urea cycle enzyme?

Answer 18

accumulation of urea cycle intermediates
glutamine levels increase in the circulation
alpha-ketoglurarate is no longer regenerated
alpha-ketoglurarate levels become too low to fix more free ammonium ion
elevated levels of ammonia in the blood are toxic for the nervous system

Question 19

What is the management of a defect in a urea cycle enzyme?

Answer 19

treatment with low-protein diet
drugs which remove nitrogen
e.g. forming complexes with amino acids which are excreted
gene therapy in hepatocytes