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MCB Lecture #69: AA Biosynth
Smith
16
Physiology
Professional
11/02/2008

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Term
What is hyperuremia and what are its effects?
Definition

In hyperuremia, the body's equilibrium is shifted towards making more glutamate and glutamine to get rid of an NH4+ buildup (highly toxic).

 

Glutamine is the only amino acid that can cross the blood-brain barrier, so the brain is still affected even though the body is protected from the NH4.

 

Newborns with this urea cycle defect become lethargic, vomit, then comatose.

 

MNEMONIC: GLUTAMINE is MEAN to the brain.

Term
What do glutamate and glutamine have to do with Amino Acid synthesis?
Definition

They act as a Nitrogen donor. They receive their N during synthesis directly from NH4+.

 

Ex: Asparagine is formed using a N from Glutamate.

Term
Recite PVT TIM HLL, the essential AA mnemonic.
Definition
Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Leucine, and Lysine.
Term
What are the six key Amino Acid synthesis precursors?
Definition

1. OAA

2. Pyruvate

3. PEP

4. 3-Phosphoglycerate

5. alpha-Ketogluterate

6. Ribose 5-Phosphate

Term
ALT/AST are key liver enzymes. What do they do?
Definition

They are both transaminases used in alanine and aspartate synthesis.

 

Pyruvate->ALT

OAA->AST

Term
In the course of amino acid synthesis, can free ammonia be found anywhere in the course of the reactions?
Definition
No. Sources such as glutamine bind nitrogen and release it directly into enzymes that contain the NH4 and transfer it safely.
Term
Name the two precursors that can be used to synthesize proline.
Definition

Glutamate OR Arginine.

 

BONUS: This reaction features a spontaneous cyclization reaction (no enzyme) that creates proline.

Term
Ornithine is an intermediate in the creation of Proline from Arginine. Can this reaction pathway be reversed?
Definition

Yes, though it requires high levels of proline. Still, Arginine can be formed from ornithine via the urea cycle.

 

Ornithine->Citrulline->Arginine

 

BONUS: Ornithine is in that sense synthetized from Proline. It can also be created from Glutamate, though this happens rarely.

Term

Serine is a precursor for what Amino Acid?

 

BONUS: Is there an allosteric mechanism in place during the synthesis of Serine?

Definition

Glycine is created from Serine.

 

BONUS: Yes. Serine undergoes a transamination reaction that is allosterically inhibited by high serine levels.

Term

Tetrahydrofolate is a key enzyme made from Folic Acid. What is its function?

 

Hint: It's reliant on oxidation states.

Definition

THF, in it's intermediate methylene (-CH2-) state, acts as a 1C donor in a variety of reactions.

 

In its reduced state, it is methyl; in it's oxidized, it is -CHO or -CH=

Term
During methanol poisoning, high doses of ethanol are given to competitively inhibit the -OH receptors. Folate is also given. Why?
Definition
Folate pushes the equilibrium of one of the intermediates of methanol metabolism, Formate, inhibiting the reaction.
Term
Where does the vast majority (95%) of methylenetetrahydrofolate come from?
Definition

Serine to Glycine synthesis.

 

Serine + THF -> Glycine + methylene-THF

 

BONUS: Glycine can also be synthesized from CO2, NH4, and methylene-THF.

Term
What is the role of SAM (S-Adenylmethionine) in AA synthesis pathways?
Definition
It is a highly reactive methyl group donor.
Term
What are the two biosynthetic reaction that require Vitamin B12?
Definition

1. Regeneration of Methionine from methyl-THF (happens in the Active Methyl Cycle)

 

2. Succinyl-CoA synthesis

 

BONUS: The active methyl cycle can only regenerate Methionine that has been modified; it does not synthesize it.

 

MNEMONIC: B12 and Meth will both make your hands tingle; that Succs!

Term

Vitamin B12 contains what heavy metal as a cofactor?

 

Hint: The clinical name of B12 is cobalamin.

Definition
Co3+ is used (similar setup to Fe in Hg). BONUS: The cobalt is attached to various sidechains (-X sidebar on slide). These are donated by the cobalt during various reactions.
Term
Methionine (regenerated via the active methyl cycle, uses SAM) is a key precursor to what amino acid?
Definition

Cysteine. Homocysteine is a key part of the active methyl cycle, of which methionine is a part.

 

Homocysteine will react with Serine to eventually form Cysteine.

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