NBME - 6/11 - Synthesis and Degradation of Amino Acids Flashcards
What amino acids are derived from glycolysis and how?
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
Primary Hyperoxaluria Type 1 - Mechanism and Effect
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.
Ketogenic vs Glucogenic Amino Acid
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
How do we make Aspartate
Derived from oxaloacetate by transamination
How do we make Asparagine?
Amidation of Aspartate
Glutamate formation
Derived from alpha-ketoglutarate by the addition of NH4+ via the glutamate dehydrogenase reaction or by transamination.
Making Glutamine
Amidation of glutamate makes glutamine
Reduction of glutamate leads to the production of what?
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.
Generating Tyrosine
Hydroxylation of phenylalanine, which requires tetrahydrobiopterin, a cofactor needed for any ring hydroxylation reaction.
Ketogenic Amino Acids
Phenyl Isolates all 3 T’s and 2 L’s
Phenylalanine
Isoleucine
Tyrosine
Threonine
Tryptophan
Leucine
Lysine
Glucogenic Amino Acids
All of them except Leucine and Lysine
Glucogenic and Ketogenic Amino Acids
Same as the Ketogenics minus the L’s
Phenylalanine
Isoleucine
Tyrosine
Threonine
Tryptophan
How can Glucose become Glycine?
Glucose to phosphoglycerate, to Serine, to Glycine
What are the essential Amino Acids
PVT TIM H(A)LL
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Leucine
Lysine
How can Acetyl CoA/Acetylacetate make glucose
Absolutely never. Otherwise we wouldn’t have this fun gluconeogenesis pathway to memorize.
Maple Syrup Urine Disease
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.
What amino acids get converted to pyruvate?
The ones that are synthesized from glycolysis intermediates become pyruvate: Serine Glycine Cysteine Alanine
Threonine to Succinyl CoA
Threonine is converted by a dehydratase to NH4+ and alpha ketobutyrate, which is oxidatively decarboxylated to propionyl CoA (precursor to succinyl CoA)
Methionine to Succinyl CoA
Methionine provides methyl groups for the synthesis of various compounds. It’s sulfur is incorporated into cysteine and the remaining carbons form Succinyl CoA
How are Phenylalanine and Tyrosine turned to Fumarate?
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.
What makes Tyrosine so great, and why might we want to stop the breakdown of Phenylalanine here at Tyrosine instead of continuing to Fumarate?
Tyrosine can become:
- Melanin
- DOPA
- NE/EPI
Discuss the basic breakdown pathway of our three BCAAs
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.
Draw Adenine (I shit you not)
What is this?
Guanine
