Liver phosphorylase

Type VI (Hers s) Liver phosphorylase Liver Enlarged liver... 

VI Hers disease Phosphorylase Liver Increased amount. Like type I, but milder course. 

VI Liver glycogen phosphorylase Liver Hepatomegaly, mild hypoglycemia, good prognosis... 

Triose Metabolism Glycogen Breakdown 16 Muscle Phosphorylase Liver Phosphorylase Phosphoglucomutase Amylo-1,6-glucosidase... 

Liver Phosphorylase. Liver phosphorylase has been highly purified but not crystallized. It has been shown to contain firmly bound phosphate that does not exchange during activity. The enzyme phosphate is lost on incubation with another inactivating enzyme, and the resulting de-phosphophosphorylase is an inactive protein of about the same size as... 

Epinephrine is a hormone that causes extremely rapid responses. One of the responses to this hormone is an increased liberation of liver glycogen as glucose. This reaction has been found to be limited by the enzyme phosphorylase. Liver phosphorylase exists as the active enzyme and as the inactive, dephosphophosphorylase. Epinephrine, and also the hyperglycemic factor, glucagon, have been found to stimulate the formation of active phosphorylase. This stimulation is mediated by an adenine nucleotide liberated from cell particles by an action of the hormones. The liberation of the nucleotide has been demonstrated in cell-free systems. The nucleotide in an unexplained manner, perhaps indirectly or after metabolic conversion to another form, alters the activity of either the kinase or the phosphatase so that the steady-state concentration of active phosphorylase is increased, i ... 

Fig. 15.3. Pathways of glycogen metabolism. 15.16, Glycogen synthetase (liver) 15.11, brancher enzyme 15.13, phosphorylase (liver) 15.15, phosphorylase kinase (liver) 15.12, phosphorylase (muscle) 15.10, debrancher enzyme (liver + muscle) 15.8, glu-cose-6-phosphatase (liver) 15.8a, glucose-6-phosphate translocase 15.5, fructose-1,6-di-phosphatase 15.9, a-glucosidase UDPGlc, uridine diphosphate glucose Glc-l-P, glucose-1-phosphate Glc-6-P, glucose-6-phosphate F-6-P, fructose-6-phosphate F-l,6-DiP, fructose- 1,6-diphosphate...

Glycogenosis type VIII (phosphorylase b kinase deficiency) gives rise to myopathy and liver disease, either singly or in combination. Phosphorylase b kinase (PBK) converts the inactive b form of both muscle and liver phosphorylases to the active a forms of the enzymes. The ischemic lactate test sometimes shows a flat result as in McArdle s disease, but is more likely to be normal. Histochemical demonstration of myophosphorylase activity in tissue sections shows a near-normal reaction due to the presence of phosphorylase a. Accumulation of glycogen is modest and found mainly in type 2 (fast-twitch glycolytic) muscle fibers. 

Type VI Hers disease Deficiency of liver phosphorylase High glycogen content in liver, tendency toward hypoglycemia. 

Type VIII Deficiency of liver phosphorylase kinase As for type VI. 

Six compounds have vitamin Bg activity (Figure 45-12) pyridoxine, pyridoxal, pyridoxamine, and their b -phosphates. The active coenzyme is pyridoxal 5 -phos-phate. Approximately 80% of the body s total vitamin Bg is present as pyridoxal phosphate in muscle, mostly associated with glycogen phosphorylase. This is not available in Bg deficiency but is released in starvation, when glycogen reserves become depleted, and is then available, especially in liver and kidney, to meet increased requirement for gluconeogenesis from amino acids. 

After intravenous administration, about 80-90% of the dose is catabolized in the liver by dihydropyrimidine dehydrogenase (DPD) [38] (Figure 14.3). The formation of the inactive 5-fluoro-5,6-dihydrouracil (5-FUH2) by DPD is the rate-limiting step of 5-FU catabolism [39]. DPD is widely distributed among tissues, with the highest levels found in the liver. Once 5-FU entered tumor cells, its antitumor effect is mainly dependent on the extent of 5-FU anabolism. After two sequential anabolic steps involving thymidine phosphorylase (TP) and thymidine kinase... 

In liver phosphorylase deficiency (glycogenosis type VI, Hers disease Fig. 42-1) and in two genetic forms of phosphorylase kinase deficiency, one of which is X-linked recessive, the other of which is autosomal recessive, hypoglycemia is either absent or mild. Symptoms of brain dysfunction do not usually occur (type VIII, Fig. 42-1) [1],... 

Cyprinus carpio 0.5 after 6 days, 300% increase in phosphorylase and 200% increase in glucose-6-phosphatase activities in liver increase in sugar level and serum lactic dehydrogenase activity 18... 

Phosphorylase was studied in depth. The enzyme from muscle was different from that catalyzing the same reaction in liver. Muscle phosphorylase but not that from liver, was activated by AMP, an early example of enzyme regulation by a ligand which was not a substrate. [Allosteric regulation was not postulated until the work of Jacob and... 

P was incorporated into specific serine residues on the phosphorylase. Similar phosphorylation activated the liver enzyme (Sutherland et al., 1956). 

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