Metabolism of alpha amino group of amino acids and urea cycle- Lecture 74

Question 1

Excess amino acids are metabolized to ______.

Answer 1

pyruvate, TCA cycle intermediates, and acetyl CoA

Question 2

Most amino acid metabolism occurs in the _____ by the _____ pathway.

Answer 2

liver

urea cycle

Question 3

Describe the pathway of the breakdown of amino acids via TA reactions that feed into the urea cycle.

Answer 3

amino groups from amino acids are collected as glutamate via transamination in muscle which can be sent to liver where glutamic dehydrogenase converts it to NH3 in a reversible reaction

Question 4

______ can be broken down by alternative pathways to TA to yield NH3.

Answer 4

serine, histidine, threonine, and cysteine

Question 5

What is the NH3 yielded from the breakdown of serine, histidine, threonine, or cysteine used for in non-liver tissue?

Answer 5

Glut + NH3 + ATP –> Gln + ADP + Pi

irreversible

Question 6

Why is the NH3 from the breakdown of serine, histidine, threonine, or cysteine in non-liver tissue used to convert Glut to Gln?

Answer 6

because it needs to get to the liver and NH3 cannot circulate through the blood because it is toxic to the brain

Question 7

What does a high BUN indicate?

Answer 7

(blood urea nitrate) indicates kidney failure

Question 8

Where do the steps of the urea cycle occur?

Answer 8

the first two steps occur in the mitochondria

steps 3-5 occur in the cytosol

Question 9

What is the first reaction of the urea cycle?

Answer 9

HCO3- + NH4+ + 2ATP –> Carbamoyl Phosphate + 2ADP

via carbamoyl phosphate synthase 1 (CSPI)

Question 10

_____ of urea is made in the first step of the urea cycle.

Answer 10

2/3

Question 11

____ is a major positive effector of the CSP-1.

Answer 11

Biochemical N-acetyl glutamic acid

Question 12

What are the final four steps of the urea cycle designed to accomplish?

Answer 12

addition of the alpha amino group of aspartate to CP to form urea
these are difficult and rate limiting

Question 13

What is the second reaction of the urea cycle?

Answer 13

Ornithine + Carbamoyl –> citrulline + Pi
via ornathine transcarbamolyase (OTC)
citrulline leaves mito

Question 14

_____ is the most common deficiency in inborn errors of the urea cycle.

Answer 14

OTC

Question 15

What is the third reaction of the urea cycle?

Answer 15

citrulline + aspartate + ATP –> argininosuccinate + ADP

via argininosuccinate synthase

Question 16

What is the fourth reaction of the urea cycle?

Answer 16

argininosuccinate –> fumarate + arginine

via argininosuccinate lyase

Question 17

What is the fifth reaction of the urea cycle?

Answer 17

arginine + H2O –> urea + ornithine
via arginase
ornithine enters mito via same carrier as citrulline in exchange and reenters cycle at reaction 2

Question 18

How can the urea cycle be linked to the TCA cycle?

Answer 18

fumarate produced in step 4 of the urea cycle can enter the TCA cycle and be converted to malate then OAA
OAA can be converted to aspartate via GOT

Question 19

What is ammonia toxicity?

Answer 19

deficiency of OTC resulting in inability of NH3 to be converted to urea for excretion

Question 20

What are the symptoms of ammonia toxicity?

Answer 20

GI tract irritability, nausea, vomiting, lethargy

if more severe, neurological disturbances, mental retardation, seizures, coma, death

Question 21

Why is NH3 toxic?

Answer 21

interference with blood pH (is basic), depletion of alpha KG out of TCA cycle (via glutamic dehydrogenase reaction), and formation of excess of the excitatory neurotransmitter glutamine (via glutamine synthase reaction)

Question 22

What treatments are available for NH3 toxicity?

Answer 22

low protein diet
maintain blood pH (acetate buffer)
clean out gut (levulose syrup)
benzoate or phenylacetate (help indirectly remove NH3)

Question 23

What is the mechanism of action of benzoate for NH3 toxicity?

Answer 23

remove glycine (NH3 –> glycine via glycine synthase)

Question 24

What is the mechanism of action of phenylacetate for NH3 toxicity?

Answer 24

remove glutamine (NH3 –> Gln via GS)