Detailed kinetic analysis of monocarboxylate transport in erythrocytes revealed that MCT1 operates through an ordered mechanism. MCT1 has a substrate binding site open to the extracellular matrix which binds a proton first followed by the lactate anion. The protein then undergoes a conformational change to a new ‘closed’’ conformation that exposes both the proton and lactate to the opposite surface of the membrane where they are released, lactate first and then the proton. For net transport of lactic acid, the rate-limiting step is the return of MCT1 without bound substrate to the open conformation. For this reason, exchange of one monocarboxylate inside the cell with another outside is considerably faster than net transport of a monocarboxylate across the membrane.
Overexpression of MCT1 has been shown to increase the efficacy of an anti-cancer drug currently undergoing clinical trials called 3-bromopyruvate in breast cancer cells.[9]
Hyperinsulinemic hypoglycemia, familial, 7 (HHF7) is an autosomal dominant disease on the SLC16A1/MCT gene on chromosome 1p13.2. It causes hyperinsulinemic hypoglycemia, where hyperinsulinism is exercise-induced.[12]
Monocarboxylate transporter 1 deficiency (MCTD1) is an autosomal dominant and recessive disease on the SLC16A1/MCT1 gene on chromosome 1p13.2. It causes poor feeding and vomiting, intellectual disability, ketotic hypoglycemia, ketoacidosis, ketonuria, with episodes brought on by fasting or infection.[13]
Erythrocyte lactate transporter defect (formerly, myopathy due to lactate transport defect) is an autosomal dominant disease on the SLC16A1/MCT gene on chromosome 1p.13.2. It causes exercise-induced muscle cramping, stiffness, and fatigue (exercise intolerance); symptoms may also be induced by heat. Although symptoms present in the muscles, muscle biopsy and EMG are normal. Decreased erythrocyte (red blood cell) lactate clearance, decreased lactate clearance from muscle after exercise, and elevated serum creatine kinase.[14]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS (Mar 1994). "Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle". Cell. 76 (5): 865–73. doi:10.1016/0092-8674(94)90361-1. PMID8124722. S2CID22137883.
Bonen A (Nov 2001). "The expression of lactate transporters (MCT1 and MCT4) in heart and muscle". European Journal of Applied Physiology. 86 (1): 6–11. doi:10.1007/s004210100516. PMID11820324. S2CID12166288.
Halestrap AP, Meredith D (Feb 2004). "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv: European Journal of Physiology. 447 (5): 619–28. doi:10.1007/s00424-003-1067-2. PMID12739169. S2CID15498611.
Rahman B, Schneider HP, Bröer A, Deitmer JW, Bröer S (Aug 1999). "Helix 8 and helix 10 are involved in substrate recognition in the rat monocarboxylate transporter MCT1". Biochemistry. 38 (35): 11577–84. doi:10.1021/bi990973f. PMID10471310.
Brooks GA, Brown MA, Butz CE, Sicurello JP, Dubouchaud H (Nov 1999). "Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1". Journal of Applied Physiology. 87 (5): 1713–8. doi:10.1152/jappl.1999.87.5.1713. PMID10562613. S2CID1484319.
Zhang GZ, Huang GJ, Li WL, Wu GM, Qian GS (Jul 2002). "[Effect of co-inhibition of MCT1 gene and NHE1 gene on proliferation and growth of human lung adenocarcinoma cells]". AI Zheng = Aizheng = Chinese Journal of Cancer. 21 (7): 719–23. PMID12479094.
Asada K, Miyamoto K, Fukutomi T, Tsuda H, Yagi Y, Wakazono K, Oishi S, Fukui H, Sugimura T, Ushijima T (2003). "Reduced expression of GNA11 and silencing of MCT1 in human breast cancers". Oncology. 64 (4): 380–8. doi:10.1159/000070297. PMID12759536. S2CID9041712.
