Monocarboxylate transporter 4

consistent citation formatting

← Previous revision Revision as of 08:13, 24 April 2026 Line 1: Line 1: {{Short description|Protein-coding gene in the species Homo sapiens}} {{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} {{Infobox_gene}} '''Monocarboxylate transporter 4''' (MCT4) also known as '''solute carrier family 16 member 3''' is a [[protein]] that in humans is encoded by the ''SLC16A3'' [[gene]].<ref name="pmid9425115">{{cite journal | vauthors = Price NT, Jackson VN, Halestrap AP | title = Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past | journal = The Biochemical Journal | volume = 329 | issue = 2 | pages = 321–8 | date = Jan 1998 | pmid = 9425115 | pmc = 1219047 | doi = 10.1042/bj3290321}}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC16A3 solute carrier family 16, member 3 (monocarboxylic acid transporter 4)| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=9123}}</ref> '''Monocarboxylate transporter 4''' (MCT4) also known as '''solute carrier family 16 member 3''' is a [[protein]] that in humans is encoded by the ''SLC16A3'' [[gene]].<ref name="pmid9425115">{{cite journal | vauthors = Price NT, Jackson VN, Halestrap AP | date = Jan 1998 | title = Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past | journal = The Biochemical Journal | volume = 329 | issue = 2 | pages = 321–328 | doi = 10.1042/bj3290321 | pmc = 1219047 | pmid = 9425115 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC16A3 solute carrier family 16, member 3 (monocarboxylic acid transporter 4)| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=9123}}</ref>

[[Northern blot|Northern]] and [[western blot]]ting and EST database analyses showed MCT4 to be widely expressed and especially so in glycolytic tissues such as white skeletal muscle fibers, [[astrocyte]]s, white blood cells, [[chondrocyte]]s, and some mammalian cell lines. Because of this, it has been proposed that the properties of MCT4 might be especially appropriate for export of lactate derived from [[glycolysis]]. MCT4 exhibits a lower affinity for most substrates and inhibitors than [[MCT1]], with Km and Ki values some 5–10-fold higher. The high Km for [[pyruvate]] may be especially significant as this avoids loss of pyruvate from the cell which, were it to occur, would prevent removal of the reduced form of [[nicotinamide adenine dinucleotide]] (NADH) produced in glycolysis by reduction of pyruvate to lactate. [[Northern blot|Northern]] and [[western blot]]ting and EST database analyses showed MCT4 to be widely expressed and especially so in glycolytic tissues such as white skeletal muscle fibers, [[astrocyte]]s, white blood cells, [[chondrocyte]]s, and some mammalian cell lines. Because of this, it has been proposed that the properties of MCT4 might be especially appropriate for export of lactate derived from [[glycolysis]]. MCT4 exhibits a lower affinity for most substrates and inhibitors than [[MCT1]], with Km and Ki values some 5–10-fold higher. The high Km for [[pyruvate]] may be especially significant as this avoids loss of pyruvate from the cell which, were it to occur, would prevent removal of the reduced form of [[nicotinamide adenine dinucleotide]] (NADH) produced in glycolysis by reduction of pyruvate to lactate.

'''MCT4''' in the brain is primarily expressed in astrocytes and microglia. Experimental studies show that astrocytes release lactate primarily via MCT4 during wakefulness, supporting orexin neuron firing and promoting wakefulness, highlighting a key role for astrocyte-derived lactate in sleep–wake regulation. <ref>{{Cite journal |last=Braga |first=Alice |last2=Chiacchiaretta |first2=Martina |last3=Pellerin |first3=Luc |last4=Kong |first4=Dong |last5=Haydon |first5=Philip G. |date=2024-07-16 |title=Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture |url=https://www.nature.com/articles/s41467-024-50166-7 |journal=Nature Communications |language=en |volume=15 |issue=1 |pages=5979 |doi=10.1038/s41467-024-50166-7 |issn=2041-1723 |pmc=11252394 |pmid=39013907}}</ref> '''MCT4''' in the brain is primarily expressed in astrocytes and microglia. Experimental studies show that astrocytes release lactate primarily via MCT4 during wakefulness, supporting orexin neuron firing and promoting wakefulness, highlighting a key role for astrocyte-derived lactate in sleep–wake regulation. <ref>{{cite journal | vauthors = Braga A, Chiacchiaretta M, Pellerin L, Kong D, Haydon PG | date = July 2024 | title = Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture | journal = Nature Communications | volume = 15 | issue = 1 | page = 5979 | doi = 10.1038/s41467-024-50166-7 | pmc = 11252394 | pmid = 39013907 }}</ref>

MCT4 can be [[Downregulation and upregulation|upregulated]] by [[HIF1A|HIF-1α]] and [[AMP-activated protein kinase|AMPK]].<ref name="pmid32144120">{{cite journal | vauthors = Felmlee MA, Jones RS, Morris ME | title = Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease | journal = [[Pharmacological Reviews]] | volume = 72 | issue = 2 | pages = 466–485 | date = 2020 | doi = 10.1124/pr.119.018762 | pmc = 7062045 | pmid = 32144120}}</ref> MCT4 can be [[Downregulation and upregulation|upregulated]] by [[HIF1A|HIF-1α]] and [[AMP-activated protein kinase|AMPK]].<ref name="pmid32144120">{{cite journal | vauthors = Felmlee MA, Jones RS, Morris ME | title = Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease | journal = Pharmacological Reviews | volume = 72 | issue = 2 | pages = 466–485 | date = 2020 | doi = 10.1124/pr.119.018762 | pmc = 7062045 | pmid = 32144120}}</ref>

== See also == == See also == Line 18: Line 19: == Further reading == == Further reading == {{refbegin | 2}} {{refbegin | 2}} * {{cite journal | vauthors = Halestrap AP, Price NT | title = The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation | journal = The Biochemical Journal | volume = 343 | issue = 2 | pages = 281–99 | date = Oct 1999 | pmid = 10510291 | pmc = 1220552 | doi = 10.1042/0264-6021:3430281 }} * {{cite journal | vauthors = Halestrap AP, Price NT | date = Oct 1999 | title = The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation | journal = The Biochemical Journal | volume = 343 | issue = 2 | pages = 281–299 | doi = 10.1042/0264-6021:3430281 | pmc = 1220552 | pmid = 10510291 }} * {{cite journal | vauthors = Halestrap AP, Meredith D | title = The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond | journal = Pflügers Archiv: European Journal of Physiology | volume = 447 | issue = 5 | pages = 619–28 | date = Feb 2004 | pmid = 12739169 | doi = 10.1007/s00424-003-1067-2 | s2cid = 15498611 }} * {{cite journal | vauthors = Halestrap AP, Meredith D | date = Feb 2004 | title = The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond | journal = Pflugers Archiv | volume = 447 | issue = 5 | pages = 619–628 | doi = 10.1007/s00424-003-1067-2 | pmid = 12739169 | s2cid = 15498611 }} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Maruyama K, Sugano S | date = Jan 1994 | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | doi = 10.1016/0378-1119(94)90802-8 | pmid = 8125298 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | date = Oct 1997 | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–156 | doi = 10.1016/S0378-1119(97)00411-3 | pmid = 9373149 }} * {{cite journal | vauthors = Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP | title = CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression | journal = The EMBO Journal | volume = 19 | issue = 15 | pages = 3896–904 | date = Aug 2000 | pmid = 10921872 | pmc = 306613 | doi = 10.1093/emboj/19.15.3896 }} * {{cite journal | vauthors = Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP | date = Aug 2000 | title = CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression | journal = The EMBO Journal | volume = 19 | issue = 15 | pages = 3896–3904 | doi = 10.1093/emboj/19.15.3896 | pmc = 306613 | pmid = 10921872 }} * {{cite journal | vauthors = Philp NJ, Wang D, Yoon H, Hjelmeland LM | title = Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells | journal = Investigative Ophthalmology & Visual Science | volume = 44 | issue = 4 | pages = 1716–21 | date = Apr 2003 | pmid = 12657613 | doi = 10.1167/iovs.02-0287 | doi-access = }} * {{cite journal | vauthors = Philp NJ, Wang D, Yoon H, Hjelmeland LM | date = Apr 2003 | title = Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells | journal = Investigative Ophthalmology & Visual Science | volume = 44 | issue = 4 | pages = 1716–1721 | doi = 10.1167/iovs.02-0287 | pmid = 12657613 }} * {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }} * {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | date = Nov 2006 | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–648 | doi = 10.1016/j.cell.2006.09.026 | doi-access = free | pmid = 17081983 | s2cid = 7827573 }} * {{cite journal | vauthors = Wang Q, Morris ME | title = The role of monocarboxylate transporter 2 and 4 in the transport of [[gamma-Hydroxybutyric acid]] in mammalian cells | journal = Drug Metabolism and Disposition | volume = 35 | issue = 8 | pages = 1393–9 | date = Aug 2007 | pmid = 17502341 | doi = 10.1124/dmd.107.014852 | s2cid = 11072905 }} * {{cite journal | vauthors = Wang Q, Morris ME | date = Aug 2007 | title = The role of monocarboxylate transporter 2 and 4 in the transport of [[gamma-Hydroxybutyric acid]] in mammalian cells | journal = Drug Metabolism and Disposition | volume = 35 | issue = 8 | pages = 1393–1399 | doi = 10.1124/dmd.107.014852 | pmid = 17502341 | s2cid = 11072905 }} {{refend}} {{refend}}

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[[Category:Solute carrier family]] [[Category:Solute carrier family]]


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