Phosphomannomutase 1,2 (PMM1,2)

Abstract

Phosphomannomutase (PMM) belongs to the family of isomerases and is involved in early mannose metabolism. It is ubiquitous and found in microbes, plants, and animals. It reversibly catalyzes the conversion of mannose-6-phosphate (Man-6-P) to mannose-1-phosphate (Man-1-P) that is required for GDP-mannose (GDP-Man) and dolichol phosphate mannose (Dol-P-Man) synthesis. GDP-mannose is essential for N-glycosylation of proteins, microbial cell wall polysaccharides, and L-ascorbic acid synthesis in plants. Dol-P-Man is required for N-glycosylation, GPI anchors O- and C-mannosylation. In many organisms, a single gene encodes both PMM and phosphoglucomutase (PGM) activities. PGM interconverts 1- and 6-glucose phosphate isomers. The presence of such bifunctional PMM/PGM enzymes in T. brucei, G. lamblia, P. aeruginosa, etc., is an example of evolutionary convergence (Lee et al. 2012). There are two mammalian isozymes - PMM1 and PMM2. We will focus mainly on human PMM2 due to its medical relevance and compare it with PMM1 in certain instances.