Molecules Derived from Amino Acids:- Biological Amines Are Products of Amino Acid Decarboxylation
Many important neurotransmitters are primary or secondary amines, derived from amino acids in simple pathways. In addition, some polyamines that form complexes with DNA are derived from the amino acid ornithine, a component of the urea cycle. A common denominator of many of these pathways is amino acid decarboxylation, another PLP-requiring reaction.
The synthesis of some neurotransmitters is illustrated in Figure 1. Tyrosine gives rise to a family of catecholamines that includes dopamine, norepinephrine, and epinephrine. Levels of catecholamines are correlated with, among other things, changes in blood pressure. The neurological disorder Parkinson’s disease is associated with an underproduction of dopamine, and it has traditionally been treated by administering L-dopa. Overproduction of dopamine in the brain may be linked to psychological disorders such as schizophrenia. Glutamate decarboxylation gives rise to γ-amino butyrate (GABA), an inhibitory neurotransmitter. Its underproduction is associated with epileptic seizures.
FIGURE 1 Biosynthesis of some neurotransmitters from amino acids. The key step is the same in each case: a PLP-dependent de carboxylation (shaded in pink).
Polyamines such as spermine and spermidine, in volved in DNA packaging, are derived from methionine and ornithine by the pathway shown in Figure 2. The first step is decarboxylation of ornithine, a precursor of arginine. Ornithine decarboxylase, a PLP-requiring enzyme, is the target of several powerful inhibitors used as pharmaceutical agents.
FIGURE 2 Biosynthesis of spermidine and spermine. The PLP dependent decarboxylation steps are shaded in pink. In these reactions, S-adenosylmethionine (in its decarboxylated form) acts as a source of propylamino groups (shaded blue).
