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Biomedical subjects

P C Calder

Publications and source records attributed to P C Calder.

At least 145 records · Page 8Linked to original sources
PubMed1990

Post mortem glycogenolysis is a combination of phosphorolysis and hydrolysis.

1. Glycogen, glucose, lactate and glycogen phosphorylase concentrations and the activities of glycogen phosphorylase a and acid 1,4-alpha-glucosidase were measured at various times up to 120 min after death in the liver and skeletal muscle of Wistar and gsd/gsd (phosphorylase b kinase deficient) rats and Wistar rats treated with the acid alpha-glucosidase inhibitor acarbose. 2. In all tissues glycogen was degraded rapidly and was accompanied by an increase in tissue glucose and lactate concentrations and a lowering of tissue pH. In the liver of Wistar and acarbose-treated Wistar rats and in the skeletal muscle of all rats glycogen loss proceeded initially very rapidly before slowing. In the gsd/gsd rat liver glycogenolysis proceeded at a linear rate throughout the incubation period. Over 120 min 60, 20 and 50% of the hepatic glycogen store was degraded in the livers of Wistar, gsd/gsd and acarbose-treated Wistar rats, respectively. All 3 types of rat degraded skeletal muscle glycogen at the same rate and to the same extent (82% degraded over 2 hr). 3. In Wistar rat liver and skeletal muscle glycogen phosphorylase was activated soon after death and the activity of phosphorylase a remained well above the zero-time level at all later time points, even when the rate of glycogenolysis had slowed significantly. Liver and skeletal muscle acid alpha-glucosidase activities were unchanged after death. 4. The decreased rate and extent of hepatic glycogenolysis in both the gsd/gsd and acarbose-treated rats suggests that this process is a combination of phosphorolysis and hydrolysis. 5. Glycogen was purified from Wistar liver and skeletal muscle at various times post mortem and its structure investigated. Fine structural analysis revealed progressive shortening of the outer chains of the glycogen from both tissues, indicative of random, lysosomal hydrolysis. Analysis of molecular weight distributions showed inhomogeneity in the glycogen loss; in both tissues high molecular weight glycogen was preferentially degraded. This material is concentrated in lysosomes of both skeletal muscle and liver. These results are consistent with a role for lysosomal hydrolysis in glycogen degradation.

Acarbose↗
PubMed1989

Acarbose is a competitive inhibitor of mammalian lysosomal acid alpha-D-glucosidases.

Intraperitoneal injections (approximately 400 mg/kg of body weight) of acarbose, an inhibitor of acid (1----4)-alpha-D-glucosidase, perturb the metabolism of glycogen in the liver, resulting in excess storage of lysosomal glycogen. The metabolism of skeletal muscle glycogen was unaffected, suggesting that acarbose either does not enter the tissue or that the muscle alpha-D-glucosidase is not inhibited. The hydrolysis of maltose and glycogen by the acid alpha-D-glucosidases from rat liver, rat skeletal muscle, and human placenta was inhibited competitively by acarbose. Thus, the lack of effect of acarbose upon the metabolism of muscle glycogen is due to its inability to enter the tissue.

Acarbose↗
PubMed1989

Rat skeletal muscle lysosomes contain glycogen.

1. A lysosome- and mitochondria-enriched fraction was obtained from rat skeletal muscle using a differential centrifugation procedure. This fraction contained a proportion (3-4%) of the tissue glycogen content. 2. Lysosomes and mitochondria were separated from one another by centrifugation of a cell-free extract upon discontinuous Ficoll-sucrose gradients. Little glycogen was associated with the resulting mitochondrial fraction. The lysosomal fraction, however, contained a significant amount of glycogen, accounting for 5% of the skeletal muscle glycogen. 3. The lysosomal glycogen was purified and found to be enriched in high molecular weight material. 4. The compartmentation of skeletal muscle glycogen metabolism is suggested.

Acid Phosphatase↗
PubMed1989

Regulation of lysosomal glycogen metabolism: studies of the actions of mammalian acid alpha-glucosidases.

1. Acid alpha-glucosidases were purified to homogeneity from rat liver, rat skeletal muscle and human placenta. The properties of these enzymes were investigated. 2. Their pH optima for activity toward various substrates were in the range 4-5. 3. Time course and pH dependence experiments revealed that all glycogen substrates were not hydrolysed at the same rate; the rate of hydrolysis was inversely related to the molecular size of the substrate. The most rapidly hydrolysed glycogen substrate was the smallest (commercial oyster) while the least rapidly hydrolysed was the largest (native rat or rabbit liver). Intermediate sized glycogens were hydrolysed at intermediate rates. 4. Glycogen hydrolysis was stimulated by added sodium ions; this stimulation was pH dependent. 5. It is suggested that lysosomal glycogen metabolism may be controlled by pH, salt concentration and the size of the glycogen substrate. 6. Since the high molecular weight glycogen associated with lysosomes is formed by disulphide bridges between lower molecular weight material it is proposed that an important step of lysosomal glycogen degradation is disulphide bond reduction.

Animals↗
PubMed1989

Skeletal muscle glycogen content, structure, and metabolism are normal in rats with hepatic glycogen phosphorylase kinase deficiency.

Skeletal muscle glycogen content and structure, and the activities of several enzymes of glycogen metabolism are reported for the hepatic glycogen phosphorylase b kinase deficient (gsd/gsd) rat. The skeletal muscle glycogen content of the fed gsd/gsd rat is 0.50 +/- 0.11% tissue wet weight, and after 40 hours of starvation this value is lowered 40% to 0.30 +/- 0.05% tissue wet weight. In contrast the gsd/gsd rat liver has an elevated glycogen content which remains high after starvation. The skeletal muscle phosphorylase b kinase, glycogen phosphorylase, glycogen synthase and acid alpha-glucosidase activities are 17.2 +/- 2.9 units/g tissue, 119.9 +/- 6.4 units/g tissue, 12.2 +/- 0.4 units/g tissue and 1.4 +/- 0.4 milliunits/g tissue, respectively, with approx. 20% of phosphorylase and approx. 24% of synthase in the active form (at rest). These enzyme activities resemble those of Wistar skeletal muscle, and again this contrasts with the situation in the liver where there are marked differences between the Wistar and the gsd/gsd rat. Fine structural analysis of the purified glycogen showed resemblance to other glycogens in branching pattern. Analysis of the molecular weight distribution of the purified glycogen indicated polydispersity with approx. 66% of the glycogen having a molecular weight of less than 250 X 10(6) daltons and approx. 25% greater than 500 X 10(6) daltons. This molecular weight distribution resembles those of purified Wistar liver and skeletal muscle glycogens and differs from that of the gsd/gsd liver glycogen which has an increased proportion of the low molecular weight material.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The structure of the rat liver glycogen backbone protein.

Rat liver glycogen was freed of non-covalently bound protein. The backbone protein was purified from the pure glycogen. This protein had a molecular weight of 60,000 daltons and amino acid analysis showed it to be rich in glutamate, serine and the hydrophobic amino acids. In both size and amino acid content it differed from the corresponding rabbit muscle protein. An O-type glycoprotein linkage is suggested.

Amino Acids↗
PubMed1985

Glycogen of high molecular weight from mammalian muscle.

Glycogen of high molecular weight has been isolated from mammalian muscle, in contrast to the material of low molecular weight commonly described. The large polysaccharide is similar to liver glycogen in the structure of its individual beta-particles and also, partially, in the mode of assembly into the gross alpha-particles. The large particles may be disrupted by 2-mercaptoethanol, but not to the same extent as their liver counterparts.

Animals↗
PubMed1983

Ordered synthesis and degradation of liver glycogen involving 2-amino-2-deoxy-D-glucose.

The incorporation of 2-amino-2-deoxy-D-glucose from precursor 2-amino-2-deoxy-D-galactose into liver glycogen has been shown to be a metabolically inhomogeneous process after starvation. The protein-to-polysaccharide ratio is also heterogeneous with respect to molecular size, and enhanced overall as compared to normal glycogen. The results are discussed from the viewpoint of a molecular order in the synthesis and degradation of liver glycogen.

Animals↗
PubMed1980

The specificity of actinidin and its relationship to the structure of the enzyme.

The kinetic parameters kcat, Km and kcat/Km, have been determined for the actinidin-catalysed hydrolyses of N-substituted amino acid esters and amides and compared to the corresponding values for papain (EC 3.4.22.2). Substrates with aromatic N-substituents have lower kcat/Km values for actinidin (EC 3.4.22.14); the difference is much smaller for substrates with aliphatic substituents. The lower kcat/Km values for actinidin generally correspond to higher Km values suggesting that the strength of substrate binding differs between the two enzymes. This difference is explained in terms of the differences in the substrate binding sites found in X-ray crystallographic studies.

Binding Sites↗
PubMedDate not supplied

The structure of placental glycogen.

Glycogen was purified from human term placenta and its structural features investigated. The beta-amylolysis limit and average chain lengths indicated that some degradation of the glycogen had occurred prior to its extraction. The sedimentation coefficient distribution of the purified glycogen showed that it contained a significant proportion of aggregated material. Diffusion coefficient measurements allowed calculation of the molecular weight distribution. The placental glycogen contained a significant proportion of high molecular weight material, although not as much as liver or skeletal muscle glycogens. Because the high molecular weight glycogen of liver and skeletal muscle is associated with the lysosome it is likely that this is also true of the large placental glycogen. Lysosomal glycogen is degraded hydrolytically to glucose and so placental glycogen may be involved in fetal glucose homeostasis.

Chemical Phenomena↗