Activation of glycolysis by zinc is diminished in hepatocytes from metallothionein-null mice.
The influence of hepatic metallothionein (MT) and zinc (Zn) on glycolysis was investigated in primary cultures of mouse hepatocytes prepared from MT-normal (+/+) and MT-null (-/-) mice. In MT +/+ mice, a close relationship was observed between the Zn concentration in the incubation medium (10-150 microM), increased MT levels in the cells, and increased glycolysis (accumulation of lactate + pyruvate) over 24 h, with significant effects seen at physiological levels of Zn (10-25 microM). Hepatocytes from MT -/- mice had significantly lower basal rates of glycolysis and demonstrated increased glycolysis only at Zn concentrations of 50 microM or greater. The lactate:pyruvate ratio was higher in the MT +/+ hepatocytes. The oxidation of endogenous fatty acid (accumulation of the ketone bodies, 3-hydroxybutyrate and acetoacetate) was initially greater in the MT +/+ hepatocytes, although only MT -/- hepatocytes showed increased ketone body production in response to Zn. The 3-hydroxybutyrate:acetoacetate ratio was higher in the MT +/+ hepatocytes and increased with increasing Zn concentrations. Intracellular Zn accumulation was 60% greater in the MT +/+ hepatocytes, with approximately 80% of the extra Zn associated with MT. The results implicate MT-associated Zn rather than increased intracellular Zn per se in the regulation of hepatic carbohydrate metabolism.
Rofe
A M
AM
Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, Australia SA.
Philcox
J C
JC
Coyle
P
P
D000818:Animals; D050260:Carbohydrate Metabolism; D002478:Cells, Cultured; D006019:Glycolysis / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015032:Zinc / Q000494:pharmacology*
D008668:Metallothionein; D015032:Zinc