Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and enolase activity and isoenzymes in lung, colon and liver carcinomas

Abstract

SummaryWe have compared the levels of phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and enolase activities and the distribution of their isoenzymes in normal colon, liver and lung tissues, and in colon, liver and lung adenocarcinoma, lung squamous cell carcinoma and lung carcinoid. All tumours presented higher phosphoglycerate mutase and enolase activities and lower 2,3-bisphosphoglycerate phosphatase activity than the normal tissues. No changes were observed in the phosphoglycerate mutase isoenzyme patterns analysed by cellulose acetate electrophoresis. All specimens contained mainly type BB isoenzyme, traces of type MB isoenzyme and no type MM isoenzyme. However, the tumours had decreased levels of 2,3-bisphosphoglycerate mutase and 2,3-bisphosphoglycerate mutase-phosphoglycerate mutase hybrid enzyme. Determined by agarose gel electrophoresis, aa-enolase was the isoenzyme predominant in normal lung, colon and liver tissue, although ay-and yy-enolase were also present in all tissues. In colon, liver and non-endocrine lung tumours, the proportions of ay-and yy-enolase decreased. In contrast, in carcinoid tumours of the lung, the proportions of these isoenzymes increased.Keywords: 2,3-bisphosphoglycerate mutase; 2,3-bisphosphoglycerate phosphatase; enolase; phosphoglycerate mutase; isoenzyme; lung, colon and liver adenocarcinoma; lung squamous cell carcinoma; lung carcinoid Phosphoglycerate mutase (D-phosphoglycerate 2,3-phosphomutase, EC 5.4.2.1, PGM) and enolase (2-phospho-D-glycerate hydrolyase, EC 4.2.1.11) are glycolytic enzymes that catalyse consecutive reversible reactions connecting the two ATP-generating reactions in the glycolytic pathway. PGM catalyses the conversion of 3-phosphoglycerate, product of the first ATP-generating reaction, into 2-phosphoglycerate in the presence of the cofactor 2,3-bisphosphoglycerate. Enolase catalyses the conversion of 2-phosphoglycerate into phosphoenolpyruvate, substrate of the second ATP-generating reaction. In addition to the main mutase activity, PGM possesses collateral 2,3-bisphosphoglycerate synthase or 2,3-bisphosphoglycerate mutase activity (BPGM: 1,3-bisphosphoglycerate + 3-phosphoglycerate -> 3-phosphoglycerate + 2,3-bisphosphoglycerate) and 2,3-bisphosphoglycerate phosphatase activity (BPGP: 2,3-bisphosphoglycerate --3-phosphoglycerate + Pi), which is stimulated by 2-phosphoglycolate (for reviews, see Fothergill-Gilmore and Watson, 1989;Wold, 1971).In mammalian tissues, there are three isoenzymes of PGM, which result from the homodimeric and the heterodimeric combinations of two different subunits coded by separate genes and designated M (muscle) and B (brain). In early fetal life, type BB-PGM is the only form present. During myogenesis, the isoenzyme phenotype undergoes transition, type BB-PGM being replaced by the MM-form, through the MB isoenzyme. In skeletal muscle, there is an almost complete transition from the BB-to the MM-PGM, but in heart muscle complete transition does not occur (Omenn and Cheung, Omenn and Hermodson, 1975;Adamson, 1...

Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and creatine kinase activity and isoenzymes in human brain tumours

“…In other tumours, PGM and CK activities did not vary in parallel. We have previously found that colon, liver and lung adenocarcinomas, lung squamous cell carcinomas and lung carcinoids had higher PGM activity than the normal tissues (Durany et al, 1997). In contrast, colon and lung adenocarcinomas and squamous cell carcinomas of the lung presented lower CK activity than the normal tissue.…”

“…PGM activity was determined by coupling the formation of 2-phosphoglycerate from 3-phosphoglycerate with the enolase-, pyruvate kinase-and lactate dehydrogenase-catalysed reactions (Beutler, 1975), as previously described (Durany and Carreras, 1996). BPGP activity was assayed by measuring the appearance of inorganic phosphate from 2,3-bisphosphoglycerate, as previously reported (Durany et al, 1997). Enzyme activities were expressed as U g-' wet tissue and as U mg-' protein (1 U = 1 g.mol substrate converted per min).…”

Protein profiles associated with survival in lung adenocarcinoma

“…Proteins such a phosphoglycerate mutase (PGAM1), an enzyme that catalyzes the reversible reaction of 3-phosphoglycerate to 2-phosphoglycerate in the glycolytic pathway, was elevated in tumors showing pleural surface involvement and angiolymphatic invasion (Table 5), consistent with unfavorable prognosis. PGAM1 is expressed in multiple cancer types including lung cancer (26). PGAM1 immunoreactivity was observed in lung tumor cells, and it was marginally predictive of survival in our validation lung tumor series.…”

Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal cancer

“…This upregulation takes place at the RNA and protein level, as well as at the level of enzymatic activities (Durany et al, 1997;Eigenbrodt et al, 1997;Mazurek et al, 2000;Hegde et al, 2001;Atsumi et al, 2002;Birkenkamp-Demtroder et al, 2002;Williams et al, 2003). In addition, in the case of the glycolytic enzyme pyruvate kinase, a loss of the tissue-specific isoenzymes (L-PK in the liver, M1-PK in muscle and brain and R-PK in erythrocytes) and expression of the pyruvate kinase isoenzyme type M2 (M2-PK) is described in all tumours investigated thus far ( Figure 1A) (Staal and Rijksen, 1991;Mazurek et al, 1997;Steinberg et al, 1999).…”