|Topic:||Phosphoglycerate Mutase .|
|Details:|| The remaining reactions of glycolysis are aimed at converting the relatively low energy phosphoacyl-ester of 3PG to a high-energy form and harvesting the phosphate as ATP. The 3PG is first converted to 2-phosphoglycerate (2PG) by phosphoglycerate mutase (PGAM) and the 2PG conversion to phosphoenolpyruvate (PEP) is catalyzed by enolase (ENO).
There are two phosphoglycerate mutase encoding genes in humans identified as PGAM1 and PGAM2. The PGAM1 gene is ubiquitously expressed, whereas, the PGAM2 encoded protein is expressed primarily in muscle tissues and for this reason is sometimes identified as PGAM-M. The PGAM1 encoded enzyme was initially characterized from brain tissue and is, therefore, often referred to as the PGAM-B isoform. The PGAM1 gene is located on chromosome 10q24.1 and is composed of 5 exons that generate two alternatively spliced mRNAs, both of which encode distinct protein isoforms. PGAM1 isoform 1 is 254 amino acids and isoform 2 is 239 amino acids. The PGAM2 gene is located on chromosome 7p13 and is composed of 3 exons that encode a protein of 253 amino acids. Mutations in the PGAM2 gene are associated with glycogen storage disease type 10.
Biologically active PGAM enzyme is a dimeric protein that contains different proportions of subunits encoded by the PGAM1 and PGAM2 genes. The most abundant form of PGAM contains only the PGAM1 encoded protein (also identified as PGAM-BB, where the BB represents homodimeric brain isoform). The predominant form of PGAM in muscle tissues, as expected, is the PGAM-MM homodimeric isoform generated from the PGAM2 gene product.
Humans express two additional genes that are members of the PGAM gene family, neither of which encode proteins with phosphoglycerate mutase activity. The PGAM4 gene (originally identified as PGAM3) is an intronless gene located on the X chromosome (Xq21.1) within the first intron of the ATP7A gene. The PGAM4 gene appears to have arisen as a result of a retrotranspostitional event and evidence suggests that the gene encodes a potentially functional protein. The PGAM5 gene is located on chromosome 12q24.33 and encodes a protein that was originally characterized as a mitochondrially localized Ser/Thr phosphatase. More recent studies have demonstrated that the PGAM5 encoded protein also functions as a member of the histidine phosphatase family of enzymes.
COPYRIGHT ©2019 . All Rights Reserved.