Key result
Cardiac myocytes share a monocarboxylate carrier for lactate and pyruvate with high affinity for pyruvate.
Demonstrated the presence of a novel monocarboxylate carrier in cardiac myocytes distinct from that in erythrocytes and hepatocytes.
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Identifies a cardiac monocarboxylate carrier in guinea pigs; leaves open its human relevance and therapeutic potential.
Time courses for the uptake of L-lactate, D-lactate and pyruvate into isolated cardiac ventricular myocytes from guinea pig were determined at 11 degrees C or 0 degrees C (for pyruvate) in a citrate-based buffer by using a silicone-oil-filtration technique. These conditions enabled initial rates of transport to be measured without interference from metabolism of the substrates. 2. At a concentration of 0.5 mM, transport of all these substrates was inhibited by approx. 90% by 5 mM-alpha-cyano-4-hydroxycinnamate; at 10 mM-L-lactate a considerable portion of transport could not be inhibited. 3. Initial rates of L-lactate and pyruvate uptake in the presence of 5 mM-alpha-cyano-4-hydroxycinnamate were linearly related to the concentration of the monocarboxylate and probably represented diffusion of the free acid. The inhibitor-sensitive component of uptake obeyed Michaelis-Menten kinetics, with Km values for L-lactate and pyruvate of 2.3 and 0.066 mM respectively. 4. Pyruvate and D-lactate inhibited the transport of L-lactate, with Ki values (competitive) of 0.077 and 6.6 mM respectively; the Ki for pyruvate was very similar to its Km for transport. The Ki for alpha-cyano-4-hydroxycinnamate as a non-competitive inhibitor was 0.042 mM. 5. These results indicate that L-lactate, D-lactate and pyruvate share a common carrier in guinea-pig cardiac myocytes; the low stereoselectivity for L-lactate over D-lactate and the high affinity for pyruvate distinguish it from the carrier in erythrocytes and hepatocytes. The metabolic roles for this novel carrier in heart are discussed.
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Poole et al. (1989) studied this question. alpha-cyano-4-hydroxycinnamate vs. Control was evaluated on Transport kinetics (Km and Ki) of L-lactate, D-lactate and pyruvate uptake. L-lactate, D-lactate and pyruvate share a common carrier in guinea-pig cardiac myocytes with low stereoselectivity for L-lactate and high affinity for pyruvate.
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