SLC16A3,7,8 cotransport monocarboxylates, H+ from extracellular region to cytosol

Stable Identifier
R-HSA-433698
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
MCTs mediate proton-coupled transport of monocarboxylates and ketone bodies
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Four members of the SLC16A gene family encode classical monocarboxylate transporters, MCT1-4. They all function as proton-dependent transporters of monocarboxylic acids such as lactate and pyruvate and ketone bodies such as acetacetate and beta-hydroxybutyrate. These processes are crucial in the regulation of energy metabolism and acid-base homeostasis.

SLC16A1 encodes MCT1, a ubiquitiously expressed protein (Garcia et al. 1994). Defects in SLC16A1 are the cause of symptomatic deficiency in lactate transport (SDLT), resulting in an acidic intracellular environment and muscle degeneration (Merezhinskaya et al. 2000). Activating promotor mutations in SLC16A1 are associated with exercise-induced hyperinsulinism (EIHI), a dominantly inherited hypoglycemic disorder characterized by inappropriate insulin secretion during anaerobic exercise or on pyruvate load (Otonkoski et al. 2000). SLC16A7 encodes MCT2, a high affinity pyruvate transporter highly expressed in testis (Lin et al. 1998). SLC16A8 encodes MCT3 (Yoon et al. 1999).

Human RPE (retinal pigment epithelial) cells express two proton-coupled monocarboxylate transporters: MCT1 in the apical membrane and MCT3 in the basolateral membrane. This suggests that the coordinated activities of these two transporters could facilitate the transepithelial transport of lactate from the retina to the choroid. (Philip et al. 2003). MCTs require the binding of a single transmembrane glycoprotein (either embigin (EMB) or basigin (BSG)) for activity (Halestrap 2013).

Literature References
PubMed ID Title Journal Year
9786900 Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter

Lin, RY, Vera, JC, Chaganti, RS, Golde, DW

J Biol Chem 1998
12657613 Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells

Philp, NJ, Wang, D, Yoon, H, Hjelmeland, LM

Invest Ophthalmol Vis Sci 2003
10493836 Cloning of the human monocarboxylate transporter MCT3 gene: localization to chromosome 22q12.3-q13.2

Yoon, H, Donoso, LA, Philp, NJ

Genomics 1999
24265240 Monocarboxylic acid transport

Halestrap, AP

Compr Physiol 2013
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Catalyst Activity
Title
monocarboxylic acid transmembrane transporter activity of SLC16A7:EMB,SLC16A3,8:BSG [plasma membrane]
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