PLP METABOLISM

Cornell University, Ithaca NY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pyridoxal 52-phosphate (PLP) is the active form of vitamin B6. PLP acts to stabilize carbanion intermediates and plays important roles in amino acid metabolism, taking part in decarboxylation, racemization, and transamination reactions. Much work has been done to characterize the biosynthesis of this very important cofactor, which occurs in bacteria and plants, but not in humans. Two pathways have been identified for the formation of PLP. The first pathway is found in E. coli and a few other bacteria and consists of two enzymes catalyzing the conversion of 3-phosphohydroxy-1-aminoacetone and 1-deoxy-D-xylulose 5-phosphate to PLP in two steps. The second pathway is more common, and takes glyceraldehyde 3-phosphate and ribose 5-phosphate to form PLP and uses glutamine as the ammonia source. YaaD and YaaE form a complex where YaaE acts as the glutaminase and shuttles ammonia to YaaD, the PLP synthetase domain. This enzyme complex has been determined to 2.9 [unreadable] and this work was published in Biochemistry in 2006 (F. Zein). Certain bacteria have been identified as being able to grow when supplied with PLP as the sole carbon and nitrogen source. Recently, Mesorhizobium loti has been shown to catabolize PLP to form succinic semialdehyde, which can then be used as a carbon source via the TCA cycle. This degradative pathway consists of seven enzymatic steps, and the enzymes responsible for each have now been identified. The fifth step is the decarboxylation of 2-methyl-3-hydroxypyridine-4,5-dicarboxylate to form 2-methyl-3-hydroxypyridine-5-carboxylate. The enzyme has been identified and structurally characterized to 1.9 [unreadable] (Mukherjee, Biochemistry 2007). The product of this reaction then undergoes an oxidative ring opening and hydrolysis to produce succinic semialdehyde.