Liver glucose phosphorylation

Pharmacokinetics Fructose Fructose is slowly absorbed from the Gl tract. Metabolized in liver by phosphorylation and partly converted to liver glycogen and glucose. Excreted in urine. Dextrose Dextrose is rapidly absorbed from Gl tract. Distributed and stored throughout tissues. Metabolized in liver to carbon dioxide and water. 

It previously has been pointed out that, potentially, PP glucose phosphotransferase and ATP-glucose phosphotransferase activities of glucose-6-phosphatase are the most potent glucose phosphorylating systems which have been characterized for liver (9, 10, 41, 118). Such a conclusion appears to have possible validity principally at and below pH 7 however (see Fig. 9) because of the nature of the pH-activity profiles of the phosphatase-associated phosphotransferase activities. 

Glycogen phosphorylase is controlled allosterically by several molecules. In the muscle, AMP is an allosteric activator. In the liver, glucose is an allosteric inhibitor. Glycogen phosphorylase also exists in a phosphorylated form and an unphosphorylated form, with the phosphorylated form being more active. 

In liver the situation is different studies of the effect of insulin on glucose phosphorylation have revealed the existence of two hexokinases—the classical hexokinase and glucokinase. Of these two, only the glucoki-nase is decreased in alloxan diabetes and responds to insulin injection (see section on metabolic regulation in Chapter 16). 

In rat liver, the phosphorylation of fructose by means of ATP occurs at a greater rate than that of glucose. It is inferred that fructokinase predominates in this tissue, and this is supported by the observation that the anaerobic degradation of glucose by rat liver slices is relatively slow. An active fructokinase has been isolated from this tissue, and in contrast to yeast hexokinase, phosphorylates at Ci. The product, fructose-1-phosphate, had previously been isolated after autolysis of liver, during fructose utilization in liver or intestine, or after enzymatic hydrolysis of fructose 1,6-diphosphate by bone phosphatase. It may be noted that both fructose-l-phosphate and fructose-6-phosphate are formed in the latter procedure. The phosphate linkage at Ci is far more labile to acid than is that at Ce. 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

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