Protein & Amino Acid Metabolism

Question 1

What do all of the amino acid catabolic pathways include?

Answer 1

Removal of amino group (transamination/deamination) - converted to urea. C skeleton is converted.

Question 2

Define ketogenic

Answer 2

Amino acids that produce acetyl~coA - acetyl can be used to synthesise ketone bodies

Question 3

Define glucogenic

Answer 3

Amino acids that produce other products which can be used for gluconeogenesis

Question 4

What are the enzymes involved in transamination and what are they stimulated by?

Answer 4

Aminotransferases, stimulated by cortisol

Question 5

What does glutaminase catalyse?

Answer 5

It’s a high specificity enzyme that converts glutamine to glutamate and NH3

Question 6

What does glutamate dehydrogenase catalyse?

Answer 6

Glutamate + NAD+ + H2O —> alpha-keto glutarate + NH4 + NADH + H+

Question 7

What is phenylketonuria?

Answer 7

Inherited disorder in which the urine contains large amounts of phenylketones produced from phenylalanine. Defective phenylalanine hydroxylase.

Question 8

How do you diagnose PKU?

Answer 8

Detection of phenylketones in the urine or high phenylalanine blood conc.

Question 9

How do you treat PKU?

Answer 9

Diet which is low in phenylalanine

Question 10

What is homocysinuria?

Answer 10

CBS enzyme is defective. Autosomal recessive disease.

Question 11

How do you diagnose homocystinuria?

Answer 11

Increase in homocysteine in plasma (some of which is converted to methionine). High levels of homocystine in urine.

Question 12

What are the effects of PKU if untreated?

Answer 12

Inhibition of brain development due to pyruvate uptake by phenylpyruvate

Question 13

What are the effects of homocystinuria if untreated?

Answer 13

Disorders of connective tissue, muscle, CNS and CVS. Can be confused for Marfan’s in children

Question 14

Why might a measure of creatinine in the blood be useful?

Answer 14

Indicative of muscle wastage

Question 15

What are the effects of hyperammonia?

Answer 15

Blurred vision, slurred speech and coma which eventually leads to death

Question 16

What are the essential amino acids?

Answer 16

Lysine, isoleucine, leucine, threonine, valine, tryptophan, phenylalanine and methionine (to produce tyrosine you need phenylalanine)

Question 17

How is excess ammonia toxic?

Answer 17

Reacts with alpha-ketoglutarate to form glutarate in mitochondria via glutamate dehydrogenase, thus removing alpha-ketoglutarate from the TCA cycle, which slows down. Affects pH and interferes with neurotransmitter release

Question 18

What effect does phenylpyruvate have on the brain?

Answer 18

Prevents uptake of pyruvate in the brains mitochondria

Question 19

Outline ammonia detoxification in the liver and the kidney

Answer 19

Question 20

Outline nitrogen metabolism

Answer 20

Question 21

Why is urea more favourable than ammonia?

Answer 21

It’s non-toxic, metabollically inert and has a high nitrogen content (therefore can be used to excrete unwanted N)

Question 22

Write an overall equation for the urea cycle

Answer 22

HCO3- + NH4+ + aspartate + 3 ATP —> CO(NH2)2 + fumarate + 2 ADP + AMP + 4Pi

Question 23

How is urea synthesis regulated?

Answer 23

There is no feedback inhibition, however the enzymes are inducible - high-protein diet.

Question 24

What can defects in the urea cycle lead to?

Answer 24

Hyperammonaemia, accumulation of a certain product. Can lead to vomiting, lethargy and irritability. Usually have mental retardation and in severe cases seizures or death.