Transfer RNA and the formation of the heme and chlorophyll precursor, 5-aminolevulinic acid

Abstract

5-Aminolevulinic acid is the first committed precursor for the synthesis of porphyrins such as hemes and chlorophylls. In many organisms aminolevulinate is synthesized from glutamate in a three-step pathway (C5 pathway). The key step in this conversion is a tRNA-mediated reduction of glutamate to glutamate-1-semialdehyde. tRNA is a specific cofactor for an NADPH-dependent enzyme, Glu-tRNA reductase, which is capable of sequence-specific recognition of Glu-tRNA(Glu). tRNA(Glu) is a dual-function molecule; it participates both in protein and in aminolevulinate biosynthesis. This reduction reaction represents a novel role for tRNA where it participates in a metabolic conversion of its amino acid into a low molecular weight metabolite which is subsequently not used in peptide bond synthesis.