Molecular pathology of glucose-6-phosphatase.
It was known in the 1950s that hepatic microsomal glucose-6-phosphatase plays an important role in the regulation of blood glucose levels. All attempts since then to purify a single polypeptide with glucose-6-phosphatase activity have failed. Until recently, virtually nothing was known about the molecular basis of glucose-6-phosphatase or its regulation. Recent studies of the type 1 glycogen storage diseases, which are human genetic deficiencies that result in impaired glucose-6-phosphatase activity, have greatly increased our understanding of glucose-6-phosphatase. Glucose-6-phosphatase has been shown to comprise at least five different polypeptides, the catalytic subunit of glucose-6-phosphatase with its active site situated in the lumen of the endoplasmic reticulum; a regulatory Ca2+ binding protein; and three transport proteins, T1, T2, and T3, which respectively allow glucose-6-phosphate, phosphate, and glucose to cross the endoplasmic reticulum membrane. Purified glucose-6-phosphatase proteins, immunospecific antibodies, and improved assay techniques have led to the diagnosis of a variety of new type 1 glycogen storage diseases. Recent studies of the type 1 glycogen storage diseases have led to a much greater understanding of the role and regulation of each of the glucose-6-phosphatase proteins.
Burchell
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Dundee University Medical School, Ninewells Hospital, Scotland, United Kingdom.
D001692:Biological Transport; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D005953:Glycogen Storage Disease Type I / Q000145:classification / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008862:Microsomes, Liver / Q000201:enzymology; D011487:Protein Conformation; D013398:Sudden Infant Death / Q000209:etiology
D005952:Glucose-6-Phosphatase; D005947:Glucose