Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle.
Lactate and pyruvate cross cell membranes via a monocarboxylate transporter (MCT) with well-defined properties but undefined molecular structure. We report the cloning of a cDNA encoding MCT1, a monocarboxylate transporter whose properties resemble those of the erythrocyte MCT, including proton symport, trans acceleration, and sensitivity to alpha-cyanocinnammates. A Phe to Cys substitution in MCT1 converts it to Mev, a mevalonate transporter. MCT1 is abundant in erythrocytes, cardiac muscle, and basolateral intestinal epithelium. In skeletal muscle it is restricted to mitochondria-rich myocytes. As sperm traverse the epididymis, MCT1 switches from sperm to epithelial cells. MCT1 is present at low levels in liver, suggesting another MCT in this tissue. By exporting lactate from intestine and erythrocytes, MCT1 participates in the Cori cycle. It also participates in novel pathways of monocarboxylate metabolism in muscle and sperm.
Garcia
C K
CK
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Goldstein
J L
JL
Pathak
R K
RK
Anderson
R G
RG
Brown
M S
MS
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002264:Carboxylic Acids / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D005455:Fluorescent Antibody Technique; D006863:Hydrogen-Ion Concentration; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism
D002264:Carboxylic Acids; D002352:Carrier Proteins; D011773:Pyruvates; D008798:Mevalonic Acid