Amino Acids Metabolism

Question 1

Ammonia Toxicity

Answer 1

• liver failure- treated with dietary restriction. As little protein as possible, and only essential amino acids
• in some inborn errors of metabolism- effects of ammonia intoxication are primarily on the nervous system, leading to dizziness, coma, convulsion

Question 2

Possible Mechanisms of Ammonia Toxicity

Answer 2

• brain glutamate dehydrogenase forms glutamate from alpha ketoglutarate and NH3, lowering brain pools of alpha ketoglutarate; hence flux through the TCA cycle is reduced
• increased glutamate leads to increased glutamine from the excess NH3. Brain pools of glutamate decrease. Glutamate is a neurotransmitter in the brain and is a precursor of GABA (GABA levels fall in the brain)
• glutamine leaves brain neurons in exchange for tryptophan. Trp is converted to serotonin a neurotransmitter. High serotonin is thought to be an important factor in coma associated with liver failure
• Summary: uncontrolled changes in the levels of 3 neurotransmitters (glutamate, GABA, and serotonin) in the brain

Question 3

Symptoms of ammonia toxicity

Answer 3

• irritability
• vomiting
• lethargy and confusion
• respiratory distress
• migraines

Question 4

Purpose of degradation of AA carbon skeletons

Answer 4

• removal of nitrogen (already covered)

- disposal of carbon skeletons to harvest energy

Question 5

Ketogenic amino acid

Answer 5

-Ketogenic- amino acids are degraded to either acetyl coenzyme A or acetoacetyl coA, which give rise to ketone bodies -lysine(K) and leucine (L)

Question 6

Glucogenic amino acid

Answer 6

• amino acids are degraded to pyruvate or citric acid cycle intermediates, which can give rise to glucose via formation of phosphoenolpyruvate
• A,R,D,N,C,E,Q,G,H,M,P,S,T,V

Question 7

Ketogenic and Glucogenic

Answer 7

• some amino acids can be degraded into multiple intermediates which can be classified as ketogenic and glucogenic
• I,F,Y,W,T

Question 8

Three carbon amino acid, threonine and glycine converted to pyruvate

Answer 8

• Alanine is converted to pyruvate by transamination with alpha ketoglutarate by alanine transaminase
• serine is converted to pyruvate by direct deamination by serine dehydratase (three pathways for degradation of, this is the major one)
• cysteine can be converted by pyruvate by a desulfhydrase in many steps
• glycine is converted by serine hydroxymethyltransferase to serine which is then converted to pyruvate; glycine can also be broken down into carbon dioxide and free ammonia by glycine cleavage enzyme
• threonine (4 carbon aa) is converted via aminoacetone to glycine then to serine and so on to make pyruvate (acetyl CoA molecule is generated), enzyme theronine dehydrogenase

Question 9

Five carbon amino acids are converted to glutamate which is converted to alpha- ketoglutarate by oxidative deamination by glutamate dehydrogenase

Answer 9

• glutamine- converted to glutamate by glutaminase, then converted to alpha ketogluterate
• histidine-converted to glutamate by a series of reaction that include transfer of its formino group to tetrahydrofolate
• arginine- converted to ornithine, and then glutamate semialdehyde and then to glutamate
• proline- it is also converted to glutamate semialdehyde and then to glutamate

Question 10

Degradation of branched chain amino acids

Answer 10

• valine, leucine and isoleucine each are converted to their corresponding alpha-keto acid by the actions of transaminases
• branched chain AA tranaminase deficiency in mice has been shown to cause increased insulin sensitivity, increased protein turnover
• all three recognized by branched chain keto acid dehydrogenase which catalyzes the oxidative decarboxylation, uses cofactors lipoamide, thiamine pyrophosphate, FAD, NAD
• the three CoA derivatives are then degraded by different pathways to yield different final products

Question 11

Maple syrup urine disease

Answer 11

• branched chain ketoaciduria
• caused by a defect in branched chain keto acid dehydrogenase
• the build up of these keto acids give the urine a characteristic odor for which the disease is named
• treatment includes dietary restriction of these amino acids
• in addition some patients will respond to high doses of thiamine

Question 12

Catabolism of amino acids to succinyl CoA

Answer 12

-methionine, isoleucine, and valine are degraded by different pathways to form succinyl CoA via methylmalonyl CoA

Question 13

Catabolism of Phenylala

Answer 13

h