Lactate transport and glycolytic activity in the freshly isolated rabbit cornea.
Studies on the intact avascular cornea reveal two types of lactate effluxes: exogenous glucose-elicited and spontaneous. The former type exhibits characteristics resembling the proton-lactate symport system previously found in tumor cells and erythrocytes, including an enhanced lactate efflux at a higher extracellular pH and in the presence of H+ and K+ ionophores, and an inhibition by mersalyl with subsequent lactate accumulation in the tissue and cessation of glycolytic activity. The latter type occurs immediately following the incubation of freshly isolated cornea in a medium containing no exogenous glucose, with a rate about 10 times that of exogenous glucose-elicited lactate efflux. It is insensitive to 10 mM iodoacetate and lacks the characteristics of the proton-lactate symport system. Findings reveal that about 50% of corneal glucose utilization occurs in the epithelium, with the stroma and endothelium sharing the other 50% approximately equally. Of the glucose utilized, the lactate formation to pyruvate oxidation rate ratios are approximately 1:1 in the epithelium, 2:1 in the stroma, and 1:2 in the endothelium. About 79% of total tissue lactate is formed in the epithelium and stroma, and in vivo, this is probably pumped into the stromal extracellular space (about 90% of total tissue volume) via the proton-lactate symport system, with spontaneous release into the aqueous humor via a simple diffusion process. The H+ and K+ ionophores facilitate lactate efflux at the expense of the cellular pyruvate pool, without significant effect on the glucose uptake and glycolytic activity. These findings suggest that the ionophore-mediated lactate efflux favors the reduction of low pyruvate concentration in the tissue, rather than parallel increases in glycolytic activity.
Biochemistry Laboratory, Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
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D019325:3-O-Methylglucose; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003315:Cornea / Q000378:metabolism*; D004728:Endothelium, Corneal / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006096:Gramicidin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D008297:Male; D008634:Mersalyl / Q000494:pharmacology; D008757:Methylglucosides / Q000378:metabolism; D009550:Nigericin / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D011817:Rabbits; D014634:Valinomycin / Q000494:pharmacology
D007773:Lactates; D008757:Methylglucosides; D011773:Pyruvates; D006096:Gramicidin; D019325:3-O-Methylglucose; D014634:Valinomycin; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D008634:Mersalyl; D009550:Nigericin