Adaptation of Red Cell Enzymes and Intermediates in Metabolic Disorders

Abstract

The metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.

Erythrocyte O2 Transport and Metabolism and Effects of Vitamin B6 Therapy in Type II Diabetes Mellitus

“…The mechanisms underlying the relationship of erythrocyte ATP and 2,3-DPG to HbA lc levels remain to be defined. The few erythrocyte enzyme activities evaluated in this study were normal or increased, confirming previous reports and suggesting the presence of young erythrocytes in peripheral blood (8,34,35,72). This may result from increased erythrocyte production and/or the shortened erythrocyte survival previously noted in diabetic subjects (77).…”

“…However, whereas ketoacidosis predictably decreases Hb-O 2 affinity and hypophosphatemia consistently lowers erythrocyte ATP and 2,3-DPG levels, findings vary in less severely decompensated subjects (2)(3)(4)(5). Thus, decreased, normal, or elevated 2,3-DPG levels; normal or increased Hb-O 2 affinity; and decreased or increased erythrocyte ATP levels have all been reported in hyperglycemic nonacidotic diabetic patients (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). These disparate findings may be due to differences in the types of diabetic subjects studied, the role of vascular disease as an independent variable, and failure to consider the effects of sex and race on Hb, Hb-O 2 affinity, and organophosphate levels in patients and healthy control subjects (15,19,21,(23)(24)(25)(26)(27).…”

“…Nonenzymatic glycosylation modifies erythrocyte membrane proteins and Hb, increasing membrane rigidity and decreasing Hb-O 2 affinity, respectively (16,(31)(32)(33). However, erythrocyte glycolytic and hexose monophosphate shunt enzymes in diabetic subjects have received only limited attention, and a role for nonenzymatic glycosylation in modifying their activities has not been explored (8,(34)(35)(36)(37).…”