Muscle pentose phosphate pathway

VLDLs to fat and muscle tissue. The NADPH necessary for lipid synthesis is obtained by oxidation of glucose in the pentose phosphate pathway. Excess amino acids are converted to pyruvate and acetyl-CoA, which are also used for lipid synthesis. Dietary fats move via the lymphatic system, as chylomicrons, from the intestine to muscle and fat tissues. 

Cells differ considerably in their use of the pentose f phosphate pathway. In muscle, a tissue in which carbohydrates are utilized almost exclusively for generation of mechanical energy, the enzymes of the pentose phosphate pathway are lacking. By contrast, red blood cells are totally dependent on the pentose phosphate pathway as a source of NADPH for which they need to keep the iron of hemoglobin in its normal +2 valence state. A deficiency in glucose-6-phosphate dehydrogenase, the first enzyme in the pentose phosphate pathway, can lead to the wholesale destruction of red blood cells and a condition known as hemolytic anemia. 

Simulation of glucose transport and glucose transporter translocation from intracellular stores to the plasma membrane in muscle cells by vanadate and peroxovan-adate involve a mechanism independent of PI-3K and protein kinase C systems utilized for stimulation of these processes by insulin. The transport of GLUT4 to the plasma membrane in muscle cells growing in culture after stimulation by vanadate, peroxovanadate, or insulin all require an intact actin network [138], Sometimes, the insulin-like action of vanadium is accompanied by overall stimulation of actual metabolic pathways. One example of this is the stimulation of the pentose phosphate pathway observed when vanadate promotes the incorporation of glucose into lipids, an antilipogenic effect [139],... 

Gl. Garcia-Bunuel, L., and Garcia-Bunuel, V. M., Connective tissue and the pentose phosphate pathway in nonnal and denervated muscle. Nature London) 213, 913-914 (1967). 

Figure 21.3 Fates of glucose 6-phosphate. Glucose 6-phosphate derived from glycogen can (1) be used as a fuel for anaerobic or aerobic metabolism as in. for instance, muscle (2) be converted into free glucose in the liver and subsequently released into the blood (3) be processed by the pentose phosphate pathway to generate NADPH or ribose n a variety of tissues.

A newborn infant has severe respiratory problems. Over the next few days, it is observed that the baby has severe muscle problems, demonstrates little development, and has neurological problems. A liver biopsy reveals a very low level of acetyl CoA carboxylase, but normal levels of the enzymes of glycolysis, gluconeogenesis, the citric acid cycle, and the pentose phosphate pathway. What is the most likely cause of the infant s respiratory problems ... 

The cardiomyopathy is directly related to a reduction in the normal biochemical function of the vitamin thiamine in heart muscle. Inhibition of the a-keto acid dehydrogenase complexes causes accumulation of a-keto acids in heart muscle (and in blood), resulting in a chemically-induced cardiomyopathy. Impairment of two other functions of thiamine may also contribute to the cardiomyopathy. Thiamine pyrophosphate serves as the coenzyme for transketolase in the pentose phosphate pathway, and pentose phosphates accumulate in thiamine deficiency. In addition, thiamine triphosphate (a different coenzyme form) may function in Na conductance channels. 

Metabolism For uptake and transport of G., see Lit. d-G. plays a central part in the carbohydrate metabolism. It is degraded to smaller molecules in complicated reaction sequences (glycolysis) with release of energy - one example is pyruvic acid, which can enter the citric acid cycle via acetyl-CoA - or (pentose phosphate pathway) can be converted to derivatives of other sugars for biosynthetic purposes under the concomitant availability of reduction equivalents. Alternatively d-G. can be stored in the liver and muscles as areserve substance glycogen (in plants starch). An antimetabolite of d-G. is 5-thio-D-glucose. For detection, see Lit.. ... 

The enzymes of the pentose phosphate pathway are widely distributed in plants, animals, and microorganisms. Recently attempts have been made to evaluate the activity of this system in vivo. Isotope experiments, in which the rate of conversion of C-1 of glucose to CO2 is compared with the rate of CO2 formation from other atoms of glucose, indicate that a major part of the oxidation in liver may proceed by the pentose pathway. In contrast, glycolysis accounts for essentially all of muscle carbohydrate metabolism. The presence of Zwischenferment, however, does not imply that this cyclic mechanism is operative, since the first steps may be used for the production of pentose phosphate for nucleotide synthesis, polysaccharides, or other purposes. 

The hexose monophosphate (Helly, 1976) and pentose phosphate (Hochachka and Hayes, 1962 Yamaguchi et al., 1976 Walsh, 1985 Malinovskaya, 1988 Kudryavtseva, 1990) shunts have also been found to increase in importance. The activity of transketolase, the enzyme which inhibits the peptide-phosphate pathway, is greater in fish from cold water, e.g. trout and smelt, than in those from warm water (Kudryavtseva, 1990). In the Black Sea horse-mackerel, a sharp decline in adenine nucleotide content (AMP, ADP and ATP) in white and red muscle tissues and in liver occurs at low temperature (Trusevich, 1978). In this case, the ATP is mosdy resynthesized by glycolysis. The increase in the glucose content of the blood of fish at low ambient temperatures may be of the same nature (Prosser, 1967 ... 

---