13- Amino Acid Metabolism

Question 1

What are the two products of aa catabolism

Answer 1

AA –> NH3(toxic) + carbon skeleton

Question 2

What do the transaminase need to work?

Answer 2

Pyridoxal-P as coenzyme

comes from Vitamin B6

Question 3

cerebral edema

Answer 3

if ammonia enters the brain.

Question 4

what can the carbon skeleton be used for?

Answer 4

Used in glycolytic pathways

Also can be used to make other things like epinephrine.

Question 5

In what two forms can NH3 be removed?

Answer 5

Urea (liver)

Ammonia (kidney)

Question 6

What are the enzymes that break down amino acids?

Answer 6

transaminases
– removes amino group

One for each amino acid (so 20)

Question 7

Urea and pathway to excretion

Answer 7

Two amino groups linked by carbonyl

MADE in the liver and dumped into blood. No transporter needed.

Will not change pH, not charged. Polar so will go through membrane.

Question 8

What happens to nitrogen in most cells?

Answer 8

NH3 + glutamate > glutamine > kidney

enzyme is glutamine synthatase

Question 9

What happens to glutamine in the kidney?

Answer 9

Glutaminase: Glutamine > glutamate + NH3

ammonium excreted in tubules
NH3 is a minor amount of excreted N

Question 10

How do we carry ammonium in the blood?

Answer 10

Always as glutamine

Because it’s non polar and doesn’t change pH

Question 11

Who is intestine tied into ammonia pathway?

Answer 11

Glutamine > intestine

Glutaminase: Glutamine > glutamate + NH3

NH3 (also from bacterial NH3) > hepatic portal vein > liver

Question 12

When does muscle use AA and what happens to it?

Answer 12

During starvation.

AA > NH3 > NH3 + a keto glutarate > glutamate > NH3 + pyruvate > alanine > blood (not change pH)

Muscles also have transaminase (pyridoxal P)

Transaminase remove amino from AA

alanine aminotransaminase: takes amino group from glutamate puts it on pyruvate > alanine

Question 13

What is alanine used for? coming from muscle

Answer 13

Alanine > liver > glutamate + pyruvate > glutamate > urea cycle

a-ketogluatarate: helps convert alanine to glutamate

Question 14

Where does urea cycle begin?

Answer 14

Liver mitochondria

Question 15

Urea cycle

Answer 15

Carbamoyl phosphatate synthetase I: NH4+ + HCO3- + 2 ATP > carbamoyl phosphotate
—- N acetyl glutamate and high protein activate it.

Orthinine Transcarbomoylase:
carbamoyl phosphate > citrulline

Question 16

BUN

Answer 16

Blood Urea Nitrogen

Decreased BUN = liver dysfunction
— either OT or CPS I might not be working correct

Increased BUN= Kidney dysfunction

Question 17

how is ammonium transported in the blood?

Answer 17

from muscle: alanine

usually: glutamine

Question 18

What other enzymes can be used to determine liver function?

Answer 18

Alanine transaminase

Aspartate transaminase

Question 19

Carbamoyl phosphate synthetase I defect

Answer 19

Hereditary, autosomal recessive

Inability for ammonia to be metabolized via urea cycle

No orotic aiduria 
hyperammonemia 
Blood glutamine increase 
BUN decreased 
Cerebral edema 
Lethargy convulsions, coma death

Question 20

Ornithine transcarbamoylase

Answer 20

Hereditary, X lined recessive

Orotic aciduria and increase uracil (gout)
hyperammonemia 
Blood glutamine increase 
BUN decreased 
Cerebral edema 
Lethargy convulsions, coma death

Question 21

Enzyme deficiencies in urea cycle

Answer 21

Complete loss = death shortly after birth

Leads to:
Hyperammonemia
Build up of glutamin and glutamate
–brain swelling and neuro problems

Treated by dietary restriction in proteins

Question 22

What is the key regulating enzyme in urea synthesis?

Answer 22

Carbamoyl phosphate synthetase I:

activated by n acetyl glutamate (NAG)

Question 23

What does the urea cycle accomplish for the body?

Answer 23

Urea synthesis provides an efficient mechanism for land animals to remove excess nitrogen from the body. Urea is synthesized in the liver and exported to the kidneys where it enters the bladder.

Question 24

Argininosuccinase deficiency

Answer 24

Inhibits flux through the urea cycle and causes hyperammonemia and neurological symptoms

Treated with a low protein diet that is supplemented with arginine, thereby resulting in argininosuccinate excretion a substitute for urea.

Question 25

What are the seven intermediates for AA biosynthesis?

Answer 25

Glycolytic:
pyruvate, 3-phosphoglycerate, phosphenolpyruvate

Pentose phosphate:
ribose-5-phosphate, erythrose-4-phosphate

citrate cycle:
a ketoglutarate, oxaloacetate

Question 26

Why is tyrosine important?

Answer 26

precursor for neurotransmitters (epinephrine, dopamine) and melanins

Tyrosine hydroxylase deficiency or no tyrosine leads to downstream of these molecules not being made

Question 27

Phenylketonuria (PKU)

Answer 27

Defect in phenylalanine hydroxylase gene (chromosome 12) is responsible for the metabolic disease. autosomal recessive

Phenylalanine hydroxylase:
Phyenylalanine > tyrosine

Symptoms:
Increase phenylalanine (30-50x higher)
urine has musty odor (phenylalanine > phenylketones)
Mental retardation

Treat:
restriction of phenylalanine in diet
–(do not drink aspartame)

Question 28

Maple syrup urine disease

Answer 28

deficiency in BRANCHED CHAIN A KETO ACID DEHYDROGENASE

produces high levels of branched chain amino acids and their a-keto acids in blood,
causing neurotoxic and potential brain damage

The a-keto acids and their metabolites are excreted in urine – maple syrup aroma

Infants exhibit feeding problems, vomiting, severe metabolic acidosis, mental retardation

and poor myelination of nerves occur

Question 29

What is treatment for maple syrup urine disease?

Answer 29

Treatment of this rare, autosomal recessive disorder involves a diet low in these amino acids
as well as dietary supplementation with keto acids and thiamine