Glycogen phosphorylase, brain form

PYGB
Identifiers
Aliases	PYGB, GPBB, phosphorylase, glycogen; brain, glycogen phosphorylase B
External IDs	OMIM: 138550; MGI: 97828; GeneCards: PYGB
Enzyme activity
Gene location (Human)
Chr.	Chromosome 20 (human)
End	25,298,012 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	150,673,678 bp
RNA expression pattern
	Top expressed in
	apex of heart; ; muscle layer of sigmoid colon; ; right hemisphere of cerebellum; ; transverse colon; ; right coronary artery; ; popliteal artery; ; tibial arteries; ; mucosa of transverse colon; ; minor salivary glands; ; right auricle of heart;
	Top expressed in
	transitional epithelium of urinary bladder; ; right ventricle; ; myocardium of ventricle; ; cardiac muscles; ; motor neuron; ; facial motor nucleus; ; atrium; ; left ventricle; ; interventricular septum; ; cardiac muscle tissue of left ventricle;
	More reference expression data
	n/a
Gene ontology
Molecular function	transferase activity; pyridoxal phosphate binding; glycogen phosphorylase activity; protein binding; catalytic activity; 1,4-alpha-oligoglucan phosphorylase activity; glycosyltransferase activity; SHG alpha-glucan phosphorylase activity; linear malto-oligosaccharide phosphorylase activity;
Cellular component	cytoplasm; extracellular exosome; membrane; extracellular region; azurophil granule lumen;
Biological process	glycogen metabolic process; metabolism; glycogen catabolic process; neutrophil degranulation; carbohydrate metabolic process;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	5834
	110078
	ENSG00000100994
	ENSMUSG00000033059
	P11216
	Q8CI94
	NM_002862
	NM_153781
	NP_002853
	NP_722476
	Wikidata
View/Edit Human	View/Edit Mouse

Glycogen phosphorylase, brain form (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]

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). 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.

Function

As a glycogen phosphorylase, GPBB catalyzes the phosphorolysis of glycogen to yield glucose 1-phosphate. This reaction serves as the rate-determining first step in glycogenolysis and, thus, contributes to the regulation of carbohydrate metabolism. In particular, GPBB is responsible for supplying emergency glucose during periods of stress, including anoxia, hypoglycemia, or ischemia. In normal cell conditions, GPBB is bound to the sarcoplasmic reticulum (SR) membrane by complexing with glycogen. When stimulated by stress conditions, Under stress conditions such as hypoxia, glycogen is degraded, and GPBB is released into the cytoplasm. 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. These other tissues also express PYGL and PYGM, but the purpose of expressing multiple glycogen phosphorylases remains unclear. Nuclear localization was also cited for GPBB in gastrointestinal cancer.

Clinical significance

Cancer

GPBB overexpression has been associated with several cancers, including colorectal cancer, gastrointestinal cancer, and non-small cell lung cancer (NSCLC). 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.

Ischemia

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

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000100994 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033059 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "PYGB phosphorylase, glycogen; brain". NCBI Entrez Gene database.
1 2 3 Newgard CB, Littman DR, van Genderen C, Smith M, Fletterick RJ (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): 3850–3857. doi:10.1016/S0021-9258(18)69003-9. PMID 3346228.
1 2 3 4 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): 255–263. doi:10.1111/j.1572-0241.2000.01692.x. PMID 10638593.
1 2 3 4 5 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): 177–185. doi:10.1016/0169-328x(89)90052-1. PMID 2615594.
1 2 3 Lee MK, Kim JH, Lee CH, Kim JM, Kang CD, Kim YD, et al. (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): 555–560. doi:10.1080/00313020601024029. PMID 17393985.
1 2 3 4 5 6 Pudil R, Vasatová M, Lenco J, Tichý M, Rehácek V, Fucíková A, et al. (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): 1193–1195. doi:10.1515/cclm.2010.231. PMID 20482380.
1 2 3 4 5 Lillpopp L, Tzikas S, Ojeda F, Zeller T, Baldus S, Bickel C, et al. (November 2012). "Prognostic information of glycogen phosphorylase isoenzyme BB in patients with suspected acute coronary syndrome". The American Journal of Cardiology. 110 (9): 1225–1230. doi:10.1016/j.amjcard.2012.06.020. PMID 22818785.
1 2 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): 553–559. doi:10.1023/A:1003239302471. PMID 9792273.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000100994 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033059 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "PYGB phosphorylase, glycogen; brain". NCBI Entrez Gene database.

[Newgard_1988-6] 1 2 3 Newgard CB, Littman DR, van Genderen C, Smith M, Fletterick RJ (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): 3850–3857. doi:10.1016/S0021-9258(18)69003-9. PMID 3346228.

[Tashima_2000-7] 1 2 3 4 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): 255–263. doi:10.1111/j.1572-0241.2000.01692.x. PMID 10638593.

[Gelinas_1989-8] 1 2 3 4 5 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): 177–185. doi:10.1016/0169-328x(89)90052-1. PMID 2615594.

[Lee_2006-9] 1 2 3 Lee MK, Kim JH, Lee CH, Kim JM, Kang CD, Kim YD, et al. (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): 555–560. doi:10.1080/00313020601024029. PMID 17393985.

[Pudil_2010-10] 1 2 3 4 5 6 Pudil R, Vasatová M, Lenco J, Tichý M, Rehácek V, Fucíková A, et al. (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): 1193–1195. doi:10.1515/cclm.2010.231. PMID 20482380.

[Lillpopp_2012-11] 1 2 3 4 5 Lillpopp L, Tzikas S, Ojeda F, Zeller T, Baldus S, Bickel C, et al. (November 2012). "Prognostic information of glycogen phosphorylase isoenzyme BB in patients with suspected acute coronary syndrome". The American Journal of Cardiology. 110 (9): 1225–1230. doi:10.1016/j.amjcard.2012.06.020. PMID 22818785.

[Uno_1998-12] 1 2 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): 553–559. doi:10.1023/A:1003239302471. PMID 9792273.