PYGB

Glycogen phosphorylase, brain (PYGB, GPBB), is an enzyme that in humans is encoded by the PYGB gene on chromosome 20. The protein encoded by this gene is a glycogen phosphorylase found predominantly in the brain. The encoded protein forms homodimers which can associate into homotetramers, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by ATP, ADP, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in glycogen degradation. [provided by RefSeq, Jul 2008][1]

Structure

The PYGB gene encodes one of three major glycogen phosphorylase isoforms, which are distinguished by their different structures and subcellular localizations: brain (PYGB), muscle (PYGM), and liver (PYGL).[2][3] GPBB is the longest of the three isozymes, with a length of 862 residues, due to the extended 3'-UTR at the enzyme's C-terminal. Nonetheless, it shares high homology in amino acid sequence with the other two isozymes, with 83% similarity with PYGM and 80% similarity with PYGL. Moreover, both its nucleotide and amino acid sequences and its codon usage share higher similarity with those of PYGM, thus indicating that the two share a closer evolutionary descent by gene duplication and translocation of a common ancestral gene. A possible pseudogene can be found on chromosome 10.[2]

Function

As a glycogen phosphorylase, GPBB catalyzes the phosphorolysis of glycogen to yield glucose 1-phosphate.[4][5] This reaction serves as the rate-determining first step in glycogenolysis and, thus, contributes to the regulation of carbohydrate metabolism.[4][6][7] In particular, GPBB is responsible for supplying emergency glucose during periods of stress, including anoxia, hypoglycemia, or ischemia.[3][4][5] In normal cell conditions, GPBB is bound to the sarcoplasmic reticulum (SR) membrane by complexing with glycogen.[7][6] When stimulated by stress conditions,[6] Under stress conditions such as hypoxia, glycogen is degraded and GPBB is released into the cytoplasm.[6] Though GPBB is primarily expressed in adult and fetal brain, it has also been detected in cardiomyocytes and at low levels in other adult and fetal tissues.[2][7][4] These other tissues also express PYGL and PYGM, but the purpose of expressing multiple glycogen phosphorylases remains unclear.[4] Nuclear localization was also cited for GPBB in gastrointestinal cancer.[8]

Clinical significance

Cancer

GPBB overexpression has been associated with several cancers, including colorectal cancer, gastrointestinal cancer, and non-small cell lung cancer (NSCLC).[3][5][8] Since GPBB is upregulated during the potential transition of adenoma cells into carcinoma cells, GPBB may be a useful biomarker to detect malignancy potential in precancerous lesions.[3]

Ischemia

Since GPBB is released from the SR membrane under ischemic conditions, it may serve as a biomarker for early detection of ischemia.[7] Specifically, its release in acute myocardial ischemia has been attributed to increased glycogenolysis and plasma membrane permeability, and has been correlated with poor outcome.[6][7] As a highly sensitive marker for myocardial ischemia, GPBB may aid in detection of perioperative myocardial damage and infarction in patients undergoing coronary artery bypass grafting. Meanwhile, GPBB levels are elevated in patients with hypertrophic cardiomyopathy.[6]

See also

References
  1. "PYGB phosphorylase, glycogen; brain". NCBI Entrez Gene database.
  2. Newgard, CB; Littman, DR; van Genderen, C; Smith, M; Fletterick, RJ (15 March 1988). "Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression, and comparison with the human liver and muscle isozymes". The Journal of Biological Chemistry. 263 (8): 3850–7. PMID 3346228.
  3. Tashima, S; Shimada, S; Yamaguchi, K; Tsuruta, J; Ogawa, M (January 2000). "Expression of brain-type glycogen phosphorylase is a potentially novel early biomarker in the carcinogenesis of human colorectal carcinomas". The American Journal of Gastroenterology. 95 (1): 255–63. PMID 10638593.
  4. Gelinas, RP; Froman, BE; McElroy, F; Tait, RC; Gorin, FA (November 1989). "Human brain glycogen phosphorylase: characterization of fetal cDNA and genomic sequences". Brain Research. Molecular Brain Research. 6 (2–3): 177–85. doi:10.1016/0169-328x(89)90052-1. PMID 2615594.
  5. Lee, MK; Kim, JH; Lee, CH; Kim, JM; Kang, CD; Kim, YD; Choi, KU; Kim, HW; Kim, JY; Park do, Y; Sol, MY (December 2006). "Clinicopathological significance of BGP expression in non-small-cell lung carcinoma: relationship with histological type, microvessel density and patients' survival". Pathology. 38 (6): 555–60. doi:10.1080/00313020601024029. PMID 17393985.
  6. Pudil, R; Vasatová, M; Lenco, J; Tichý, M; Rehácek, V; Fucíková, A; Horácek, JM; Vojácek, J; Pleskot, M; Stulík, J; Palicka, V (August 2010). "Plasma glycogen phosphorylase BB is associated with pulmonary artery wedge pressure and left ventricle mass index in patients with hypertrophic cardiomyopathy". Clinical Chemistry and Laboratory Medicine. 48 (8): 1193–5. doi:10.1515/cclm.2010.231. PMID 20482380.
  7. Lillpopp, L; Tzikas, S; Ojeda, F; Zeller, T; Baldus, S; Bickel, C; Sinning, CR; Wild, PS; Genth-Zotz, S; Warnholtz, A; Lackner, KJ; Münzel, T; Blankenberg, S; Keller, T (1 November 2012). "Prognostic information of glycogen phosphorylase isoenzyme BB in patients with suspected acute coronary syndrome". The American Journal of Cardiology. 110 (9): 1225–30. doi:10.1016/j.amjcard.2012.06.020. PMID 22818785.
  8. Uno, K; Shimada, S; Tsuruta, J; Matsuzaki, H; Tashima, S; Ogawa, M (August 1998). "Nuclear localization of brain-type glycogen phosphorylase in some gastrointestinal carcinoma". The Histochemical Journal. 30 (8): 553–9. doi:10.1023/A:1003239302471. PMID 9792273.

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