Are arterial, muscle and working limb lactate exchange data obtained on men at altitude consistent with the hypothesis of an intracellular lactate shuttle?
The "Lactate Shuttle" Hypothesis posits that lactate removal requires exchange among producing and consuming cells. The "Intra-cellular Lactate Shuttle" hypothesis posits that lactate exchange occurs among compartments within cells, and that mitochondria are the major sites of cellular lactate disposal. Thus, cells with high mitochondrial densities (cardiocytes, myocytes, hepatocytes) are those which participate in lactate clearance. The model of an Intracellular Lactate Shuttle recognizes that the Keq for LDH is 3.6 x 10(4) M-1; thus, glycolysis results in cytosolic lactate production regardless of the intracellular PO2. The model also requires presence of a mitochondrial monocarboxylate transporter (MCT) that allows uptake of lactate as well as pyruvate, and intra-mitochondrial LDH whose function is linked to the ETC, and which permits lactate-->pyruvate conversion and oxidation. Recently, we have shown that liver, heart and muscle mitochondria readily oxidize lactate and contain LDH and MCT1. Accordingly, we have concluded that lactate is the predominant monocarboxylate oxidized by mitochondria in vivo. The model of an "Intra-cellular Lactate Shuttle" is consistent with many of the observations on men at sea level and altitude. The observations include: oxidation is the primary fate of lactate disposal during rest and exercise; lactate production and oxidation occur simultaneously within resting and working muscle; increasing [lactate]a increases muscle lactate extraction, and that by increasing SaO2 acclimatization reduces blood [lactate].
Brooks
G A
GA
Department of Integrative Biology, University of California, Berkeley 94720, USA.
D000818:Animals; D001158:Arteries / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D005121:Extremities; D006801:Humans; D007773:Lactates / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*
D002352:Carrier Proteins; D007773:Lactates