Glycogen phosphorylase, brain (PYGB, GPBB), is an enzyme that in humans is encoded by the PYGBgene 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 carbohydratemetabolism.[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]
^ abcNewgard, 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. PMID3346228.
^ abcdTashima, 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. PMID10638593.
^ abcLee, 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. PMID17393985.
^ abcdefPudil, 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. PMID20482380.
^ abcdeLillpopp, 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. PMID22818785.
^ abUno, 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. PMID9792273.