Phosphoglucomutase (EC:5.4.2.2) catalyzes the interconversion of glucose-6-phosphate and glucose-1-phosphate and is important for carbohydrate metabolism in a variety of organisms, ranging from bacteria to humans (7, 8, 1, 9). The direction of the interconversion is determined by the availability of substrate carbon sources (8). Saccharomyces cerevisiae contains a major phosphoglucomutase isoform, Pgm2p, and a minor phosphoglucomutase isoform, Pgm1p. Pgm2p and Pgm1p functions are involved in glycolysis, the pentose phosphate shunt, and the metabolism of glycogen, trehalose, and galactose. Phosphoglucomutase is also required for the synthesis of N-linked glycoproteins, extracellular glycans, and UDP-glucose (7, 8, 9, 10). Phosphoglucomutase also indirectly effects calcium uptake and homeostasis because glucose-1-phosphate and glucose-6-phosphate effect cation uptake (11, 12, 8).

Pgm2p accounts for approximately 80%-90% of all phosphoglucomutase activity in S. cerevisiae. Basal expression of Pgm2p is constitutive, and expression increases in response to: heat shock during conditions of glucose repression, glucose depletion, ethanol stress, salt stress, lithium stress and during adaptation to cold (13, 7, 14, 15, 16, 17). Pgm2p expression is also induced during growth on galactose (8, 2) and at the diauxic shift (18). Induction at the diauxic transition is dependent on Msn2p/Msn4p functions (18), and induction in response to heat shock or salt stress is dependent on Msn2p/Msn4p and glycogen synthase kinase 3 (Mck1p, Mrk1p, Rim11p and Ygk3p) (15). Although Pgm2p has been shown to be post-translationally glycosylated to different degrees under different conditions (7, 3), there is no evidence that the modifications alter the enzymatic activity of Pgm2p (13). Phosphoglucomutase activity is inhibited by lithium in both yeast and humans, making it an important in vivo lithium target, as lithium is frequently used as a treatment for manic depressive disorders in humans (14). In yeast, this inhibition leads to glucose-1-phosphate accumulation during growth on galactose (19).

pgm2 null mutants are viable, but accumulate more glucose-1-phosphate and intracellular calcium during growth on galactose as compared to wild type (11). pgm2 null mutants also display increased sensitivity to toxic cations such as lithium, calcium, aminoglycosides, and polyamines (12). pgm1 pgm2 double null mutants are viable, but cannot use galactose as a sole carbon source, and accumulate lower levels of glycogen and trehalose than wild type (1). The growth phenotypes of pgm2 null mutants can be complemented by expression of E. coli phosphoglucomutase (9).

Last updated: 2005-09-08