NBME - 6/11 - Synthesis and Degradation of Amino Acids

Question 1

What amino acids are derived from glycolysis and how?

Answer 1

Serine, Cysteine, Glycine, and Alanine

3-Phosphoglycerate gets oxidized, transaminated by glutamate, and dephosphorylated to make Serine.

By losing a methylene group to THF, Serine turns to Glycine Cysteine gets its carbon and nitrogen from serine, and its sulfur from Methionine

The only one that doesn’t mooch off of 3-PG is Alanine, which is derived from transamination of pyruvate

Question 2

Primary Hyperoxaluria Type 1 - Mechanism and Effect

Answer 2

To turn Alanine to Pyruvate, we use Glycine transaminase. In the process of this reaction, we turn glyoxylate to glycine.

This disease is results from a defect in glycine transaminase, resulting in the accumulation of glyoxylate.

Glyoxylate gets oxidized to oxalate which is a little soluble, and will form calcium salts in the kidney, leading to stone formation and renal failure.

Question 3

Ketogenic vs Glucogenic Amino Acid

Answer 3

Glucogenic = C-skeleton can be converted to a gluconeogenic intermediate such as pyruvate and TCA cycle intermediates

Ketogenic = C skeleton can’t be converted to a gluconeogenic intermediate

Photogenic = Patrick McCarthy

Question 4

How do we make Aspartate

Answer 4

Derived from oxaloacetate by transamination

Question 5

How do we make Asparagine?

Answer 5

Amidation of Aspartate

Question 6

Glutamate formation

Answer 6

Derived from alpha-ketoglutarate by the addition of NH4+ via the glutamate dehydrogenase reaction or by transamination.

Question 7

Making Glutamine

Answer 7

Amidation of glutamate makes glutamine

Question 8

Reduction of glutamate leads to the production of what?

Answer 8

Glutamate semialdehyde.

Cyclization of glutamate semialdehyde gets us Proline.

Transamination of glutamate semialdehyde makes Ornithine, which in three steps of the urea cycle can generate Arginine.

Question 9

Generating Tyrosine

Answer 9

Hydroxylation of phenylalanine, which requires tetrahydrobiopterin, a cofactor needed for any ring hydroxylation reaction.

Question 10

Ketogenic Amino Acids

Answer 10

Phenyl Isolates all 3 T’s and 2 L’s

Phenylalanine

Isoleucine

Tyrosine

Threonine

Tryptophan

Leucine

Lysine

Question 11

Glucogenic Amino Acids

Answer 11

All of them except Leucine and Lysine

Question 12

Glucogenic and Ketogenic Amino Acids

Answer 12

Same as the Ketogenics minus the L’s

Phenylalanine

Isoleucine

Tyrosine

Threonine

Tryptophan

Question 13

How can Glucose become Glycine?

Answer 13

Glucose to phosphoglycerate, to Serine, to Glycine

Question 14

What are the essential Amino Acids

Answer 14

PVT TIM H(A)LL

Phenylalanine

Valine

Threonine

Tryptophan

Isoleucine

Methionine

Histidine

Leucine

Lysine

Question 15

How can Acetyl CoA/Acetylacetate make glucose

Answer 15

Absolutely never. Otherwise we wouldn’t have this fun gluconeogenesis pathway to memorize.

Question 16

Maple Syrup Urine Disease

Answer 16

Autosomal Recessive disorder with mutations in the branched chain alpha-ketoacid dehydrogenase, which is the guy that turns our Valine, Isoleucine and Leucine into products that could become CoAs.

This causes Valine, Isoleucine, and Leucine to accumulate, leading to a maple syrup odor urine with mental retardation.

Thiamine deficiency can lead to this due to its involvement with a couple of the enzymes.

Question 17

What amino acids get converted to pyruvate?

Answer 17

The ones that are synthesized from glycolysis intermediates become pyruvate: Serine Glycine Cysteine Alanine

Question 18

Threonine to Succinyl CoA

Answer 18

Threonine is converted by a dehydratase to NH4+ and alpha ketobutyrate, which is oxidatively decarboxylated to propionyl CoA (precursor to succinyl CoA)

Question 19

Methionine to Succinyl CoA

Answer 19

Methionine provides methyl groups for the synthesis of various compounds. It’s sulfur is incorporated into cysteine and the remaining carbons form Succinyl CoA

Question 20

How are Phenylalanine and Tyrosine turned to Fumarate?

Answer 20

Phenylalanine is converted to Tyrosine by Phenylalanine hydroxylase in a reaction requiring tetrahydrobiopterin and O2.

Tyrosine, obtained this way or through the diet, is turned to homogentisic acid. The aromatic ring is opened and cleaved, forming fumarate and acetoacetate.

Question 21

What makes Tyrosine so great, and why might we want to stop the breakdown of Phenylalanine here at Tyrosine instead of continuing to Fumarate?

Answer 21

Tyrosine can become:

1. Melanin
2. DOPA
3. NE/EPI

Question 22

Discuss the basic breakdown pathway of our three BCAAs

Answer 22

Valine Isoleucine and Leucine all form their alpha keto forms after transamination (in MUD, this is the final step).

Through oxidation, they form CoA derivatives and then eventually all 3 have a method of becoming Propionyl CoA (Although isoleucine can stop at Acetyl CoA and Leucine can stop at Acetoacetate + Acetyl CoA).

Propionyl CoA turns to Methylmalonyl CoA and finally Succinyl CoA. The predominant former of propionyl CoA is Valine.

Question 23

Draw Adenine (I shit you not)

Answer 23

Question 24

What is this?

Answer 24

Guanine

Question 25

What is this?

Answer 25

Cytosine

Question 26

What is this?

Answer 26

Thymine

Question 27

What is this?

Answer 27

Uracil

Question 28

What is this?

Answer 28

Deoxyribose

Question 29

Treatment of Gout early vs. late

Answer 29

Colchicine first (Acute) - It blocks phagocytosis/migration. Use especially when that patient cannot use NSAIDs, but for those who can tolerate it, both are used. Colcichine works a lot like Vincristine/Vinblastine in that it binds tubulin to stop Mitosis, thus killing inflammatory cells. It also inhibits neutrophil migration and motility to block further inflammation.

For later or chronic, use the Allopurinol