Amino Acid Metabolism 2

Question 1

Urea cycle produes urea to detoxify _____

Answer 1

NH4+ (Ammonia)

Question 2

Where does the urea cycle begin?

Answer 2

Mitochondria

Question 3

In addition to urea, what other important product is generated via the urea cycle?

Answer 3

Arginine

Question 4

___ ATP molecules are used in the mitochondria to produce carbamoyl phosphate

___ ATP molecules are used in the cytosol to produce argininosuccinate from citrulline.

Answer 4

2

1

Question 5

____ is required to activate carbamoyl phosphate synthetase 1 and links the TCA cycle and amino acid metabolism.

Answer 5

Acetylglutamate

Question 6

What do high levels of glutamate indicate?

What impact does this have on TCA cycle?

Considering this, explain how the TCA cycle and Urea cycle are linked.

Answer 6

High levels of amino acid metabolism for energy use that is outpacing the pace of the urea cycle

In order to deal with the nitrogen in AAs, AKG is converted to glutamate, so there is a decrease in AKG which will result in decreased flux through TCA.

Urea cycle decreases [glutamate] and in glutmate metabolism AKG is produced, so the urea cycle can restore the balance of TCA cycle intermediates by increasing [AKG] and allowing TCA to continue

Question 7

Acetyl coA levels will _____ if AKG is converted to Glu.

Answer 7

Increase

Question 8

What is the major presentation of urea cycle defects?

Answer 8

Hyperammonemia

Question 9

Ornithine transcarbamylase deficiency is inherited via ______ inheritance

Deficiencies in other urea cycle enzymes are inherited via ______ inheritance

Answer 9

X-linked

Autosomal recessive

Question 11

Ammonia is highly toxic to the ______ system

Answer 11

Nervous

Question 12

Defects in urea cycle enzymes are noticed at what stage of life?

Answer 12

1 - 2 days after birth (poor feeding, vomiting, coma, seizure)

Question 13

Ornithine transcarbamylase deficiency leads to production of ______

Answer 13

Orotic acid

Question 14

How does OTC deficiency impact pyrimidine synthesis?

Answer 14

When OTC is deficient, carbamoyl phosphate builds up and can leak from the mitochondria and impact pyrimidine biosynthesis

Question 15

How can hyerammonemia be treated using conjugates that are administered to a patient (2)?

Answer 15

1) In the body: ammonia can be added to glycolytic intermediate to make glycine

Drug: benzoate given –> combines with glycine to be excreted safely

2) In the body: ammonia can be added to glutamate to make glutamine

Drug: Pehnylacetate given –> combines with glutamine to be excreted safely

Question 16

The kidney can take up glutamine from the blood and convert it to glutamate producing NH4+. Why does it do this?

Answer 16

Removal of NH3 from glutamine allows the kidney to combine NH3 with H+ to produce NH4+ and thus excrete excess H+ ions in times of high [H+] in blood. Thus, the kidney produces urea directly in order to maintain pH balance.

Question 17

Describe the reason why the kidney performs gluconeogenesis.

Answer 17

Glutamate produced from glutamine degradation in kidney is converted to AKG by glutamate dehydrogenase in kidney. AKG feeds into gluconeogenesis pathway in kidney (kidney has enzymes for Gluconeogenesis). Thus, kidney is CONSTITUTIVELY performing gluconeogenesis because it is always maintaining pH balance so it is always generating AKG.

Question 18

____ is used to synthesize tyrosine.

Answer 18

Phe

Question 19

Tyrosine is non-essential as long as ___ is in excess.

Answer 19

Phe

Question 20

Degradation of tyrosine releases ___ and results in production of ___.

Answer 20

Fumarate

Acetyl-coA

Question 21

PKU is a defect in which enzyme?

Answer 21

Phenylalanine hydroxylase, which is needed to make tyrosine from Phe

Question 22

Untreated PKU is associated with ______

Answer 22

Intellectual disability

Question 23

PKU Defects

• Patients with this defect present with ___?
• What is the treatment for PKU?
• What is a clinical sign of PKU?

Answer 23

• Hyperphenylalaninemia and phenylketonuria
• Phe restricted diet
• Musty smelling urine

Question 24

Alkaptonuria is a defect in the breakdown of ______. The result is a build up of ______.

Answer 24

Tyrosine

Homogenistic acid

Question 25

What happens to the urine and bones in alkoptonuria?

Answer 25

• Urine turns black upon standing
• Build up of homogentisate results in polymerization and formation of dark pigment that is deposited in cartilage and turns joints black

Question 26

What 2 compounds is tyrosine a precursor for?

Answer 26

Catecholamines and melanin