Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Each of 12 types of glycogen storage disease (GSD O-XI) is delineated by clinical, biochemical and histologic features that allow its identification in future patients. GSD II occurs in 2 forms that are not both encountered in the same family. GSD IIa is the infantile fatal form with cardiomegaly, increased cardiac glycogen concentration and cardiac failure; GSD IIb is the adult form with clinically normal heart and normal cardiac glycogen concentration. Nonetheless, the heart muscle of both forms is equally deficient in acid alpha-glucosidase activity, and this raises questions as to the latter's role in the pathophysiology of GSD II. The appearance of hepatocytes in GSD IIa becomes normal after the administration of alpha-glucosidase. Using electron microscopy of uncultured amniotic fluid cells, the prenatal diagnosis of GSD IIa is feasible within one day after the amniocentesis. GSD VI and IX are instances of benign hepatomegaly except when GSD IX and III occur in the same child; one such patient died suddenly at home. There are 2 modes of inheritance in GSD IX: one (GSD IXa) is autosomal recessive, the other one (GSD IXb) is X-linked recessive. In either form the Km of the remaining liver phosphorylase kinase is normal. Both forms of GSD IX have the normal blood sugar response to glucagon, whereas GSD VI does not. Equally, the glucagon tolerance curve is flat in GSD XI although in vitro activity of glycolytic enzymes is normal. The in vivo administration of glucagon in GSD XI is followed by the normal increase of both urinary 3'5'-AMP and hepatic phosphorylase activity. GSD V may have increased activity of muscle phosphorylase kinase. Deficiencies of debrancher, liver phosphorylase and liver phosphorylase kinase can occur singly or in combination. Before any novel treatment of GSD is initiated, one should obtain tissue for the biochemical determination of the exact type of GSD. This is so because the clinical signs may not indicate the type with the necessary precision, and because some types are compatible with normal life and thus may not require therapy, especially if the latter is unproved and potentially dangerous.
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PMID:Glycogen storage diseases. 78 7

The prominent protein phosphatases involved in liver glycogen metabolism are the AMD (ATP, Mg-dependent, type-1) and PCS (polycation-stimulated, type-2A) phosphatases. The glycogen synthase phosphatase activity, measured from the rate of activation of liver glycogen synthase, is virtually accounted for by AMD phosphatases; the bulk of the activity belongs to the glycogen-bound protein phosphatase G and a small part is present in the cytosol. The major part of the phosphorylase phosphatase activity present in the post-mitochondrial supernatant is shared by protein phosphatase G and cytosolic enzymes, and a minor part belongs to a microsomal AMD phosphatase. In the liver cytosol, the phosphorylase phosphatase activity is about equally distributed between AMD and PCS phosphatases. Studies in vivo as well as on isolated, perfused livers have shown that glucagon (which raises the level of cyclic AMP) as well as vasopressin (which increases the cytosolic Ca2+ concentration) decrease the phosphorylase phosphatase activity in liver extract or cytosol (filtered through Sephadex G-25) by about 25% within a few minutes. These effects were not additive, and the activity of glycogen synthase phosphatase was not affected. Conversely, insulin as well as glucose increased both phosphatase activities by about 25%, and these effects were additive. Vanadate mimicked the effect of insulin on the perfused liver. All the activity changes were only observed when the assays were performed at high tissue concentration. Upon subcellular fractionation all the effects were well expressed in the cytosol, but not in the particulate fraction (glycogen and microsomes). However, quantitatively the hormonal responses were largely lost during the fractionation procedure; they could be restored by recombination of the liver cytosol from a hormone-treated rat with the particulate fraction from either a treated or an untreated animal. It appears that the effects of glucagon, insulin and glucose are mediated by cytosolic, transferable effectors of the Vmax of protein phosphatases. These effectors are eluted in the void volume of a Sephadex G-25 column. Rats of the gsd/gsd strain, which have a genetic deficiency of hepatic phosphorylase kinase, responded to an injection of insulin plus glucose with a normal increase in the cytosolic phosphorylase phosphatase activity. In contrast, they failed to respond to glucagon as well as vasopressin. A transient 80% inhibition of the phosphorylase phosphatase activity could be induced in vitro in a concentrate liver cytosol from Wistar rats upon addition of MgATP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Short-term hormonal control of protein phosphatases involved in hepatic glycogen metabolism. 216 98