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.
Chen
C H
CH
Biochemistry Laboratory, Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Chen
S C
SC
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