PFKM
6-phosphofructokinase, muscle type is an enzyme that in humans is encoded by the PFKM gene on chromosome 12. Three
Structure
Gene
This gene is found on chromosome 12.[4] The coding region in PFKM only shares a 68% similarity with that of the liver-type PFKL.[5]
Protein
This 85-kDa protein is one of two subunit types that comprise the seven tetrameric PFK isozymes.
The liver PFK (PFK-5) contains solely the second subunit type, PFKL, while the erythrocyte PFK includes five isozymes composed of different combinations of PFKM and PFKL.
Function
This gene encodes one of three protein subunits of PFK, which are expressed and combined to form the tetrameric PFK in a tissue-specific manner. As a PFK subunit, PFKL is involved in catalyzing the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. This irreversible reaction serves as the major rate-limiting step of glycolysis.[6][9][10][12]
Though the PFKM subunit majorly incorporates into muscle and erythrocyte PFKs, PFKM also is expressed in the
Clinical significance
As the erythrocyte PFK is composed of both PFKL and PFKM, this heterogeneic composition is attributed with the differential PFK activity and organ involvement observed in some inherited PFK deficiency states in which myopathy or hemolysis or both can occur, such as glycogenosis type VII, also known as Tarui disease.[6][9][14] Notably, mutations in PFKM have been shown to cause Tarui disease due to homozygosity for catalytically inactive M subunits.[7][14] PFKM is confirmed to be involved in muscle PFK deficiency with early-onset hyperuricemia.[7]
Even though PFKM functions to drive glycolysis, its overexpression has been associated with
Interactions
PFKM has been shown to
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".
See also
References
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033065 – Ensembl, May 2017
- ^ "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.
- ^ a b "Entrez Gene: PFKM phosphofructokinase, muscle".
- PMID 2533063.
- ^ PMID 6444721.
- ^ PMID 6227635.
- PMID 6445244.
- ^ S2CID 20133199.
- ^ PMID 22474333.
- PMID 21124851.
- PMID 26194095.
- S2CID 23300861.
- ^ PMID 24306210.
- PMID 12649290.
Further reading
- Raben N, Sherman JB (1995). "Mutations in muscle phosphofructokinase gene". Human Mutation. 6 (1): 1–6. S2CID 46649815.
- Kahn A, Etiemble J, Meienhofer MC, Bovin P (Jun 1975). "Erythrocyte phosphofructokinase deficiency associated with an unstable variant of muscle phosphofructokinase". Clinica Chimica Acta; International Journal of Clinical Chemistry. 61 (3): 415–9. PMID 125160.
- Zhao ZZ, Malencik DA, Anderson SR (Feb 1991). "Protein-induced inactivation and phosphorylation of rabbit muscle phosphofructokinase". Biochemistry. 30 (8): 2204–16. PMID 1825608.
- Yamasaki T, Nakajima H, Kono N, Hotta K, Yamada K, Imai E, Kuwajima M, Noguchi T, Tanaka T, Tarui S (Aug 1991). "Structure of the entire human muscle phosphofructokinase-encoding gene: a two-promoter system". Gene. 104 (2): 277–82. PMID 1833270.
- Sharma PM, Reddy GR, Babior BM, McLachlan A (Jun 1990). "Alternative splicing of the transcript encoding the human muscle isoenzyme of phosphofructokinase". The Journal of Biological Chemistry. 265 (16): 9006–10. PMID 2140567.
- Nakajima H, Kono N, Yamasaki T, Hotta K, Kawachi M, Kuwajima M, Noguchi T, Tanaka T, Tarui S (Jun 1990). "Genetic defect in muscle phosphofructokinase deficiency. Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5'-splice site". The Journal of Biological Chemistry. 265 (16): 9392–5. PMID 2140573.
- Valdez BC, Chen Z, Sosa MG, Younathan ES, Chang SH (Mar 1989). "Human 6-phosphofructo-1-kinase gene has an additional intron upstream of start codon". Gene. 76 (1): 167–9. PMID 2526044.
- Sharma PM, Reddy GR, Vora S, Babior BM, McLachlan A (Apr 1989). "Cloning and expression of a human muscle phosphofructokinase cDNA". Gene. 77 (1): 177–83. PMID 2526045.
- Nakajima H, Noguchi T, Yamasaki T, Kono N, Tanaka T, Tarui S (Oct 1987). "Cloning of human muscle phosphofructokinase cDNA". FEBS Letters. 223 (1): 113–6. S2CID 42849336.
- Vora S, Seaman C, Durham S, Piomelli S (Jan 1980). "Isozymes of human phosphofructokinase: identification and subunit structural characterization of a new system". Proceedings of the National Academy of Sciences of the United States of America. 77 (1): 62–6. PMID 6444721.
- Kahn A, Weil D, Cottreau D, Dreyfus JC (Feb 1981). "Muscle phosphofructokinase deficiency in man: expression of the defect in blood cells and cultured fibroblasts". Annals of Human Genetics. 45 (Pt 1): 5–14. S2CID 39444994.
- Vasconcelos O, Sivakumar K, Dalakas MC, Quezado M, Nagle J, Leon-Monzon M, Dubnick M, Gajdusek DC, Goldfarb LG (Oct 1995). "Nonsense mutation in the phosphofructokinase muscle subunit gene associated with retention of intron 10 in one of the isolated transcripts in Ashkenazi Jewish patients with Tarui disease". Proceedings of the National Academy of Sciences of the United States of America. 92 (22): 10322–6. PMID 7479776.
- Tsujino S, Servidei S, Tonin P, Shanske S, Azan G, DiMauro S (May 1994). "Identification of three novel mutations in non-Ashkenazi Italian patients with muscle phosphofructokinase deficiency". American Journal of Human Genetics. 54 (5): 812–9. PMID 7513946.
- Raben N, Exelbert R, Spiegel R, Sherman JB, Nakajima H, Plotz P, Heinisch J (Jan 1995). "Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency". American Journal of Human Genetics. 56 (1): 131–41. PMID 7825568.
- Raben N, Sherman J, Miller F, Mena H, Plotz P (Mar 1993). "A 5' splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease)". The Journal of Biological Chemistry. 268 (7): 4963–7. PMID 8444874.
- Howard TD, Akots G, Bowden DW (May 1996). "Physical and genetic mapping of the muscle phosphofructokinase gene (PFKM): reassignment to human chromosome 12q". Genomics. 34 (1): 122–7. PMID 8661033.
- Hamaguchi T, Nakajima H, Noguchi T, Nakagawa C, Kuwajima M, Kono N, Tarui S, Matsuzawa Y (1997). "Novel missense mutation (W686C) of the phosphofructokinase-M gene in a Japanese patient with a mild form of glycogenosis VII". Human Mutation. 8 (3): 273–5. S2CID 196597214.
- Scherer PE, Lisanti MP (Aug 1997). "Association of phosphofructokinase-M with caveolin-3 in differentiated skeletal myotubes. Dynamic regulation by extracellular glucose and intracellular metabolites". The Journal of Biological Chemistry. 272 (33): 20698–705. PMID 9252390.
- Ristow M, Vorgerd M, Möhlig M, Schatz H, Pfeiffer A (Dec 1997). "Deficiency of phosphofructo-1-kinase/muscle subtype in humans impairs insulin secretion and causes insulin resistance". The Journal of Clinical Investigation. 100 (11): 2833–41. PMID 9389749.