Co-factor for GABA, Dopamine, and Histamine ?

The neurotransmitters GABA, dopamine, and histamine are all derived from an amino acid precursor. The generation of these neurotransmitters from the appropriate amino acids requires which one of the following cofactors?

A. NAD+

B. B1

C. B2

D. B6

E. B12

Answer- The correct answer is B6.

All the neurotransmitters in question are derived by a common process of decarboxylation that requires the presence of vitamin B6 as a coenzyme.

1) GABA is derived from Glutamic acid (figure-1)

GABA FORMATION

Figure-1- Glutamic acid to GABA conversion. The reaction is catalyzed by glutamic acid decarboxylase that requires the presence of B6-P as a coenzyme .

2) Dopamine is derived from DOPA (dihydroxy phenyl alanine); it is an important step in the catecholamine  biosynthesis (Figure-2)

Dopamine synthesis

 

Figure-2- Tyrosine is a precursor of catecholamines. Dopamine is produced by the decarboxylation of DOPA. The reaction is catalyzed by Dopa decarboxylase that requires the presence of pyridoxal phosphate (B6-P).

 3) Histamine is derived from Histidine (figure-3). Histamine is an important mediator of allergies and inflammations

Histamine formation

Figure-3- Conversion of Histidine to histamine is catalyzed by histidine decarboxylase that requires the presence of B6-P as a coenzyme.

As regards other options,

  • NAD + acts as a coenzyme for the dehydrogenases. It is derived from niacin .Examples include-Glyceraldehyde-3-P dehydrogenase, Lactate dehydrogenase, PDH complex and Alpha ketoglutarate dehydrogenase complex etc.
  • B1, Thiamine in its active form as TPP is required for the oxidative decarboxylation of pyruvate (PDH complex), Alpha ketoglutarate (Alpha ketoglutarate dehydrogenase complex) and Alpha keto acids of branched chain amino acids (Alpha keto acid dehydrogenase complex). TPP is also required by Transketolase enzyme of HMP pathway.
  • B2, Riboflavin (FMN and FAD) is required by dehydrogenases and amino acid oxidases, e.g. Succinate dehydrogenase, L-amino acid oxidase etc
  • B12 is required as a coenzyme in the conversion of Homocysteine to Methionine, methyl malonyl co A to Succinyl co A and also for the activity of ribonucleotide reductase.
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