Disease relevance of PGAM1

• Overlaps of the tryptic peptides were obtained by studying the V8 Staphylococcus aureus protease peptides of the aminoethylated phosphoglycerate mutase isozyme B either by microsequencing or by mass spectrometry [1].
• Human muscle phosphoglycerate mutase (PGAM-M) deficiency is associated with exercise intolerance, muscle cramps, chronic serum CK elevation, and recurrent episodes of myoglobinuria [2].
• Hereditary muscle PGAM deficiency has been identified in 9 patients with myopathy [3].
• Nine patients with McArdle disease, one with the partial glycolytic defect phosphoglycerate mutase deficiency, and nine matched, healthy subjects performed the classic ischemic forearm protocol and an identical protocol without ischemia [4].
• The biochemical properties and mechanism of catalysis of the novel spore germination protease that degrades small, acid-soluble proteins protecting DNA against damage, a cofactor independent phosphoglycerate mutase, NAD+ synthetase, and the three know B. anthracis toxins, protective antigen, lethal factor, and edema factor are described [5].

High impact information on PGAM1

• Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy [6].
• These results support the hypothesis that cancer cells depend on glycolysis for viability and promote PGAM1 as a potential therapeutic target [7].
• The glycolytic enzyme phosphoglycerate mutase (PGAM) is a dimer, and mature human skeletal muscle contains almost exclusively the MM form of the enzyme, PGAM-M [8].
• The molecular genetic basis of muscle phosphoglycerate mutase (PGAM) deficiency [8].
• When the PGAM-M gene constructs were cotransfected with MyoD into C3H10T1/2, the profile of CAT activity was similar to that observed in C2C12 myotubes [9].

Chemical compound and disease context of PGAM1

• Muscle PGK deficiency is now added to two other newly recognized glycolytic defects, phosphoglycerate mutase and lactate dehydrogenase deficiencies, as a cause of recurrent myoglobinuria [10].
• Among the enzymes, phosphoglycerate mutase followed by creatine kinase appeared to be the most sensitive index of muscle disorder [11].
• Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and enolase activity and isoenzymes in lung, colon and liver carcinomas [12].
• For the first time, we report on phosphoglycerate mutase B in the resveratrol-treated prostate cancer cells LNCaP, DU145, and PC-3 at the transcription level [13].

Biological context of PGAM1

• This assignment shows that the PGAM2 is not syntenic with the nonmuscle form of PGAM1 (B) which has been located to chromosome 10 [14].
• Northern analysis demonstrates the non-muscle-specific nature of PGAM-B transcription, while genomic Southern analysis implies the presence of a large PGAM family in the human genome [15].
• Most of the PGAM-hybridizing sequences in both the human and mouse genomes seem to be related to the B-isozyme gene; many members of the PGAM-B gene family in humans are apparently processed genes [15].
• PGAM-B is detected in pachytene spermatocytes and in spermatids, but not in earlier stages of spermatogenesis [16].
• In situ mapping of the muscle-specific form of phosphoglycerate mutase gene to human chromosome 7p12-7p13 [17].

Anatomical context of PGAM1

• No PGAM-B activity was detected in testes of newborn mice, in which only the PGAM-AA isozyme was observed [16].
• PGAM-B might thus be useful as a marker for germ cell differentiation, along with other germ cell-specific proteins [16].
• We have previously reported the isolation in pure form of the human erythrocyte phosphoglycerate mutase isozyme B. We now report the sequence of the whole protein and the identification of its N-terminal blocking group [1].
• Analysis of metabolic activity of one of the tumor cell lines, MCF-7, indicated that PGMtide inhibited glycolytic flux, consistent with in vivo inhibition of PGM [18].
• Leukocyte activation through chemoattractant receptors leads to Pak activation and transient inhibition of endogenous PGAM-B activity [19].

Associations of PGAM1 with chemical compounds

• Human B-type 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase (dPGM-B) has been cloned, overexpressed and purified, with a yield of 30% of the total protein [20].
• Phosphoglycerate mutase (PGAM; EC 2.7.5.3) catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate in the glycolytic pathway [3].
• We found a new PGAM-M mutation in a Japanese family with partial PGAM deficiency: a G-to-A transition at nucleotide position 209, resulting in the substitution of a highly conserved glycine at codon 97 with aspartic acid (G97D) [21].
• Muscle phosphoglycerate mutase deficiency with tubular aggregates: effect of dantrolene [22].
• The specificity of the observed effect was further determined experimentally by testing the effect of PGMtide on cells growing in the presence of pyruvate, which helps to compensate PGM inhibition in the glycolytic pathway [18].

Other interactions of PGAM1

• 2,3-Bisphosphoglycerate mutase (BPGM) [EC 5.4.2.4] is a multifunctional enzyme that catalyzes both the synthesis and the degradation of 2,3-diphosphoglycerate (2,3-DPG) and contains three types of activities in that it functions as a 2,3-DPG synthetase, a phosphoglycerate mutase and a 2,3-DPG phosphatase [23].
• Types alpha gamma and gamma gamma enolase, types MB and MM phosphoglycerate mutase were detected in much lower proportions [24].
• Defects of the second step of glycolysis, phosphoglycerate kinase, phosphoglycerate mutase and lactate dehydrogenase deficiencies, have been discovered recently and are associated with exercise intolerance [25].
• Additionally, phosphoglycerate mutase (PIR: JQ0750) and ATP synthase alpha chain (PIR: S17193) were identified [26].
• A phosphoglycerate mutase brain isoform (PGAM 1) pseudogene is localized within the human Menkes disease gene (ATP7 A) [27].

Analytical, diagnostic and therapeutic context of PGAM1

• The structural gene for PGAM-M was assigned to chromosome 7p12-7p13; a single hybridization peak indicated that there is a single gene for this isozyme of PGAM, and confirmed results obtained by Southern blot hybridization [17].
• The protein tryptic peptides of phosphoglycerate mutase isozyme B were isolated by high performance liquid chromatography and their sequence determined by microsequencing [1].
• Cloning, purification, crystallization and preliminary crystallographic analysis of human phosphoglycerate mutase [20].
• Northern blot analysis showed that the expression patterns of Pgam1 and Pgam2 were distinct [28].
• The identification of multiple molecular forms of human red cell phosphoglycerate mutase and 2,3-bisphosphoglycerate synthase by isoelectric focusing [29].

References