Erythrocyte phosphoglucomutase activity of bipolar I patients currently using lithium or carbamazepine

Lithium has been used for the last five decades to treat bipolar disorder, but the molecular basis of its therapeutic effect is unknown. Phosphoglucomutase is a key enzyme in the metabolism of glycogen. In yeast, rabbit and human HEK293 cells, it is inhibited by lithium in the therapeutic concentration range. We measured the phosphoglucomutase activity in erythrocytes and the inhibitor constant for lithium in a population of healthy subjects and compared them to those of bipolar patients treated with lithium or carbamazepine. The specific activity of phosphoglucomutase measured in vitro in erythrocytes from control subjects presented a normal distribution, with the difference between the lowest and the highest activity being approximately 2-fold (0.53-1.10 nmol mg Hb-1 min-1). Comparison of phosphoglucomutase activity in untreated bipolar patients and control subjects showed no significant difference, whereas comparison between bipolar patients treated with carbamazepine or lithium revealed significantly lower mean values in patients treated with carbamazepine (747.3 ± 27.6 vs 879.5 ± 35.9 pmol mg Hb-1 min-1, respectively). When we studied the concentration of lithium needed to inhibit phosphoglucomutase activity by 50 percent, a bimodal distribution among the population tested was obtained. The concentration of LiCl needed to inhibit phosphoglucomutase activity by 50 percent was 0.35 to 1.8 mM in one group of subjects and in the other it was 3 to 4 mM. These results suggest that phosphoglucomutase activity may be significant in patients with bipolar disorder treated with lithium and carbamazepine.

Influence of exercise on the activity and the distribution between free and bound forms of glycolytic and associated enzymes in tissues of horse mackerel

The effects of short-term burst (5 min at 1.8 m/s) swimming and long-term cruiser (60 min at 1.2 m/s) swimming on maximal enzyme activities and enzyme distribution between free and bound states were assessed for nine glycolytic and associated enzymes in tissues of horse mackerel, Trachurus mediterraneus ponticus. The effects of exercise were greatest in white muscle. The activities of phosphofructokinase (PFK), pyruvate kinase (PK), fructose-1,6-bisphosphatase (FBPase), and phosphoglucomutase (PGM) all decreased to 47, 37, 37 and 67 percent, respectively, during 60-min exercise and all enzymes except phosphoglucoisomerase (PGI) and PGM showed a change in the extent of binding to subcellular particulate fractions during exercise. In red muscle, exercise affected the activities of PGI, FBPase, PFK, and lactate dehydrogenase (LDH) and altered percent binding of only PK and LDH. In liver, exercise increased the PK activity 2.3-fold and reduced PGI 1.7-fold only after 5 min of exercise but altered the percent binding of seven enzymes. Fewer effects were seen in brain, with changes in the activities of aldolase and PGM and in percent binding of hexokinase, PFK and PK. Changes in enzyme activities and in binding interactions with subcellular particulate matter appear to support the altered demands of tissue energy metabolism during exercise

Phosphoglucomutase proteins in human milk

O polimorfismo do loco 4 da fosfoglicomutase foi investigado em uma amostra de colostro obtida de 652 mulheres (60% brancas e 40% negras), coletada 24 a 48 hs. após o parto, em Porto Alegre, Brasil. Uma nova amostra de leite foi obtida de 175 dessas mulheres com cerca de 17 dias de lactaçäo. No colostro observou-se um acentuado desvio no equilíbrio de hardy-Weinberg, havendo em geral um excesso de homozigotos e deficiência de heterozigotos. No leite, no entanto, esse desequilíbrio näo ocorreu. As diferenças entre as duas distribuiçöes säo devidas à detecçäo de padröes nas amostras que näo apresentavam atividade no primeiro período, assim como a variabilidade na ativaçäo enzimática, que pode ocorrer no início da lactaçäo. As frequências gênicas no leite (n = 175) foram: brancos (n = 127) PGM4*1 = 0,20, PGM4*2 = 0,41, PGM4*3 = 0,38, PGM4*4 = 0,01; negróides (n = 48) PGM4*1 = 0,15, PGM4*2 = 0,52, PGM4*3 = 0,32 e PGM4*4 = 0,01