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

homotetramer A tetrameric protein is a protein with a protein quaternary structure, quaternary structure of four subunits (tetrameric). Homotetramers have four identical Protein subunit, subunits (such as glutathione S-transferase), and heterotetramers are M ...

s, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Air ...

, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...

degradation. rovided by RefSeq, Jul 2008ref name="entrez">

Structure

The ''PYGB'' gene encodes one of three major glycogen phosphorylase isoforms, which are distinguished by their different structures and

subcellular localization The cells of eukaryotic organisms are elaborately subdivided into functionally-distinct membrane-bound compartments. Some major constituents of eukaryotic cells are: extracellular space, plasma membrane, cytoplasm, nucleus, mitochondria, Golgi ap ...

s: brain (PYGB), muscle (PYGM), and liver (

PYGL Glycogen phosphorylase, liver form (PYGL), also known as human liver glycogen phosphorylase (HLGP), is an enzyme that in humans is encoded by the ''PYGL'' gene on chromosome 14. This gene encodes a homodimeric protein that catalyses the cleavag ...

). GPBB is the longest of the three isozymes, with a length of 862

residues Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are appli ...

, 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 Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. ...

and

translocation Translocation may refer to: * Chromosomal translocation, a chromosome abnormality caused by rearrangement of parts ** Robertsonian translocation, a chromosomal rearrangement in pairs 13, 14, 15, 21, and 22 ** Nonreciprocal translocation, transfer ...

of a common ancestral gene. A possible

pseudogene Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by Reverse transcriptase, reverse transcription of an mRNA trans ...

can be found on chromosome 10.

Function

As a glycogen phosphorylase, GPBB catalyzes the

phosphorolysis Phosphorolysis is the cleavage of a compound in which inorganic phosphate is the attacking group. It is analogous to hydrolysis.Stryer, L. (1988) Biochemistry, 3rd ed., Freeman (p. 451) An example of this is glycogen breakdown by glycogen phospho ...

of glycogen to yield glucose 1-phosphate. This reaction serves as the rate-determining first step in

glycogenolysis Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase. Mechanism The ...

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 Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...

. In normal cell conditions, GPBB is bound to the sarcoplasmic reticulum (SR) membrane by

complexing A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many m ...

with glycogen. When stimulated by stress conditions, Under stress conditions such as

hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

, 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

cardiomyocyte Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...

s 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.

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localization was also cited for GPBB in

gastrointestinal cancer Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract (GI tract) and accessory organs of digestion, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The ...

Clinical significance

Cancer

GPBB overexpression has been associated with several cancers, including

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

, and non-small cell lung cancer (NSCLC). Since GPBB is upregulated during the potential transition of

adenoma An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenom ...

cells into

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...

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

. Specifically, its release in

acute myocardial ischemia A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tra ...

has been attributed to increased

and

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

permeability, and has been correlated with poor outcome. 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 Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...

References