Amino Acid Metabolism - RR

Question 1

What are the symptoms of ammonia toxicity?

Answer 1

Irritability, vomiting, lethargy, confusion, respiratory distress, migraines

Question 2

Ammonia toxicity results in neurological symptoms. What is the proposed mechanism involving neurotransmitters that explains this?

Answer 2

1. Brain glutamate dehydrogenase converts alpha-ketoglutarate to glutamate. This decreases the amount of alpha-ketoglutarate and TCA.
2. Glutamine synthase converts glutamate to glutamine (which can store more ammonia). But need glutamate to make GABA. So lose GABA production
3. Glutamine leaves the brain in exchange for tryptophan. Tryptophan is then converted to serotonin which can lead to coma.

Question 3

When ketogenic amino acids are degraded, what is formed?

Answer 3

Acetyl CoA or acetoacetyl CoA which then gives rise to ketones

Question 4

When glucogenic amino acids are degrades, what is formed?

Answer 4

Pyruvate or CAC intermediates which can give rise to glucose

Question 5

What two amino acids are considered ketogenic?

Answer 5

leucine and lysine

Question 6

What amino acids can be degraded to eventually produce pyruvate? (there are 6)

Answer 6

Threonine, Gylcine, Tryptophan, Alanine, Serine, Cysteine

Question 7

What amino acids can be degraded to eventually produce alpha-ketoglutarate? (there are 5)

Answer 7

arginine, histidine, glutamine, proline, glutamate

Question 8

Which amino acids can be degraded to eventually produce succinyl CoA? (there are 4)

Answer 8

valine, threonine, isoleucine, methionine

Question 9

Which amino acids can be degraded to eventually produce fumarate? (there are 3)

Answer 9

aspartate, tyrosine, phenylalanine

Question 10

Which amino acids can be degraded to form oxaloacetate? (there are 2)

Answer 10

arginine, asparagine

Question 11

What amino acid can pyruvate form? What is this reaction? What enzyme performs this reaction?

Answer 11

Alanine; alanine transaminase (ALT)

Pyruvate + glutamate –> alanine + alpha-ketoglutarate

Question 12

What enzyme performs serine degradation? What is the product?

Answer 12

Serine dehydratase

Pyruvate

Question 13

There are three pathways for glycine degradation. What are they?

Answer 13

1. Glycine to serine which then goes onto pyruvate (serine hydroxymethyl transferase does this reaction)
2. Glycine to CO2 and NH4+ and 5,10-methylene THF (this is important because of the THF as a cofactor)
3. Glycine to CO2 and NH4” by glycine cleavage enzyme

Question 14

Amino acids with 4 carbons typically are converted to what CAC intermediate?

Answer 14

oxaloacetate

Question 15

Amino acids with 3 carbons are typically converted to what glycolytic intermediate?

Answer 15

pyruvate

Question 16

Amino acids with 5 carbons are typically converted to what CAC intermediate?

Answer 16

alpha-ketoglutarate (via glutamate formation)

Question 17

What two reactions use THF (tetrahydrofolate)?

Answer 17

Glycine to serine

Histidine to glutamate

Question 18

What are ALT and AST?

Answer 18

“liver enzymes”

Alanine aminotransferase and aspartate aminotransferase

Question 19

What is the pathway for arginine degradation?

Answer 19

Arginine is a product of the urea cycle. Arginase (irreversible enzyme) cleaves arginine into urea and ornithine. Ornithine is then converted to glutamate via THF and ultimately to alpha-ketoglutarate

Question 20

Branched amino acids are typically converted to what CAC intermediate?

Answer 20

succinyl-CoA

Question 21

What are the general steps in the conversion of branched amino acids into their CAC intermediate?

Answer 21

1. Branched chain transaminase converts into the AA specific keto-acid
2. The AA specific keto-acid is then converted to get the AA derivative bound to CoA - by branched-chain keto acid dehydrogenase (same mechanism as pyruvate dehydrogenase)

Question 22

A defect in what enzyme causes maple syrup disease? How is it treated?

Answer 22

Branched chain keto-acid dehydrogenase

Treatment: Dietary restriction to avoid the amino acid, in some cases high doses of thiamine

Question 23

How is tyrosine normally formed? What enzyme and what cofactor?

Answer 23

Hydroxylation of phenylalanine via phenylalanine hydroxylase with cofactor tetrahydrobiopterin

Question 24

A defect in which enzyme causes PKU? What builds up? How is it treated?

Answer 24

Defect in phenylalanine hydroxylase so phenyalanine builds up and get toxic derivatives of phenylalanine like phenylpyruvate
Treatment: diet- avoid foods with phenylalanine

Question 25

A defect in which enzyme causes atypical PKU?

Answer 25

defect in dihydrobiopterin reductase so can’t regenerate the cofactor tetrahydrobiopterin needed to hydroxylate phenylalanine

Question 26

What is maternal PKU?

Answer 26

A mother who has PKU needs to return to the PKU diet in order to avoid neurological issues for the fetus

Question 27

An enzyme in what pathway is defective in alkaptouria?

Answer 27

Conversion of phenylalanine to tyrosine

Question 28

What enzyme is deficient in alkaptonuria? What are the symptoms? How is it diagnosed?

Answer 28

Homogentisate oxidase
Symptoms: black urine and arthritis at an earlier age
Diagnosed: can see deposits when shining light onto ear lobe

Question 29

Pellagra results from a deficiency in what amino acid?

Answer 29

Tryptophan

Question 30

There are 3 methods for adding amino groups to molecules. What are these 3 methods?

Answer 30

1. transamination
2. aspartate–> fumarate
3. glutamine –> glutamate

Question 31

How is alanine formed?

Answer 31

Pyruvate converted into alanine via alanine transaminase

Question 32

How is aspartate formed?

Answer 32

Oxaloacetate converted to aspartate via aspartate transaminase

Question 33

How is asparagine formed?

Answer 33

Glutamine and aspartate combine to form asparagine

Question 34

How is glutamate formed?

Answer 34

Alpha-ketoglutarate converted to glutamate via glutamate dehydrogenase

Question 35

How is glutamine formed?

Answer 35

Glutamate and ammonia group combine to form glutamine

Question 36

How is arginine formed?

Answer 36

Glutamate breaks down into ornithine which is then converted to arginine

Question 37

How is proline formed?

Answer 37

From glutamate

Question 38

How is serine formed?

Answer 38

From 3-phosphoglycerate

Question 39

How is glycine formed?

Answer 39

From serine via serine hydroxymethyltransferase

Question 40

How is cysteine formed?

Answer 40

Serine and methionine combine to form cysteine

Cysteine is only nonessential if there’s enough methionine in the diet

Question 41

What is homocysteinuria? Cystathionuria? What are the consequences?

Answer 41

Both are inherited deficiencies where can’t convert methionine and serine into cysteine.
Homocysteinuria: mutation in cystathionine synthase
Cystathiouria: mutation in cystathiose
Both have increased atherosclerosis and increased risk of dying from MI at young age