Biochemistry-Bioactive Amines Flashcards
What are the three main cofactors in nitrogen metabolism and what do they generally do?
Pyridoxal phosphate (PLP: 10+ rxns), Tetrahydrobiopterin (BH4: ring hydroxylations) and S-Adenosylmethionine (SAM: methylating agent)
Why is pyridoxal phosphate (PLP) so versatile in the number of reactions it can carry out with amino acids?
The aldehyde of PLP forms a Schiff base with the amino acid that can go on to do many different things.
What reaction is most often carried out by PLP in formation of bioactive amines?
Your are going from an amino acid to an amine, so obviously you would decarboxylate the amino acid.
How does tetrahydrobiopterin (BH4) relate to mental retardation?
Any defect in the pathway of converting phenylalanine to tyrosine via phenylalanine hydroxylase and the reduced oxygen produced by BH4 will result in phenylketonuria (PKU). This causes build up of toxic Phe intermediates and inability to make neurotransmitters from Tyr.
What cofactor is crucial in methylation of amino acids?
SAM
Why might kids with PKU tend to sunburn more easily than other kids?
Phe hydroxylase is involved in converting Phe to Tyr. Tyr is needed for production of melanin.
How is epinephrine synthesized from phenylalanine in the adrenal medulla?
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What enzymes are involved in inactivating bioactive amines?
COMT (SAM methylates hydroxyl groups) and MAO (shown below)
What do you need to resynthesize SAM?
Folate and B12
What is the mechanism of the MAO reactions?
FAD oxidizes the amine to a Schiff base which is hydrolyzable to an aldehyde and ammonia.
In the disposal of norepinephrine, does MAO or COMT need to act first?
Either can act first. If MAO goes first you release ammonium and form the aldehyde group. The aldehyde group is oxidized and then COMT methylates a hydroxyl group to form VMA (vanillylmandelic acid). If COMT foes first, you methylate the hydroxy group. Then MAO releases NH4+ and oxidizes the aldehyde group to an acid. Either way you get VMA.
How is serotonin made from tryptophan?
First, BH4 hydroxylates the ring. Next PLP decarboxylates the molecule to form serotonin.
How do you inactivate serotonin?
1st MAO relases NH3 and forms the aldehyde group. Then NAD+ oxidizes the molecule to an acid.
How is histamine made from histidine?
PLP decarboxylates histidine.
How is histamine cleared?
1) SAM methylates histamine, then MAO releases NH4+ and forms the aldehyde, then NAD+ forms Methylimidazole Acetic acid. 2) NH4+ is released by diamine oxidase and then NAD+ oxidizes it to imidazole acetic acid in peripheral tissues.
How is ACh formed? How is it cleared?
Acetyl CoA is transfered to choline via choline acetyltransferase. It is cleared by acetycholinesterase.
What is the structure of glutamate?
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How is GABA made from glutamate in neurons?
PLP decarboxylates glutamate
How is GABA recycled in astrocytes?
1) GABA transaminase converts GABA into succinate semi-aldehyde (SSA) 2) SSA is oxidized to succinate 3) It hops in the citric acid cycle and forms alpha-ketoglutarate 4) Another transamination reaction form glutamate
What must the astrocyte to in order to transport glutamate back to the neurons?
Convert it to glutamine. Glutamine is not an active bioamine.
