Muscle, skeletal transferase

The liver and to a lesser extent the kidneys, contain glucose 6-phosphatase, whereas muscle and the brain do not. Hence, muscle and the brain, in contrast with the liver, do not release glucose. Another key enzymatic difference is that the liver has little of the transferase needed to activate acetoacetate to acetoacetyl CoA. Consequently, acetoacetate and 3-hydroxybutyrate are exported by the liver for use by heart muscle, skeletal muscle, and the brain. 

HCN is detoxified to thiocyanate (SCN ) by the mitochondrial enzyme rhodanese rhodanese catalyzes the transfer of sulfur from thiosulfate to cyanide to yield thiocyanate, which is relatively nontoxic (Smith 1996). The rate of detoxification of HCN in humans is about 1 pg/kg/min (Schulz 1984) or 4.2 mg/h, which, the author states, is considerably slower than in small rodents. This information resulted from reports of the therapeutic use of sodium nitroprusside to control hypertension. Rhodanese is present in the liver and skeletal muscle of mammalian species as well as in the nasal epithelium. The mitochondria of the nasal and olfactory mucosa of the rat contain nearly seven times as much rhodanese as the liver (Dahl 1989). The enzyme rhodanese is present to a large excess in the human body relative to its substrates (Schulz 1984). This enzyme demonstrates zero-order kinetics, and the limiting factor in the detoxification of HCN is thiosulphate. However, other sulfur-containing substrates, such as cystine and cysteine, can also serve as sulfur donors. Other enzymes, such as 3-mercapto-pyruvate sulfur transferase, can convert... 

There are five enzymes that are commonly used in diagnosis of liver disease Aspartate aminotransferase (AST EC 2.6.1.1), alanine aminotransferase (ALT EC 2.6.1.2), alkaline phosphatase (ALP 3.1.3.1), and y-glutamyl transferase (GGT EC 2.3.2.2), are commonly used to detect liver injury, and lactate dehydrogenase (LD EC 1.1.1.27) is occasionaEy used. ALT and GGT are present in several tissues, but plasma activities primarily reflect liver injury. AST is found in liver, muscle (cardiac and skeletal), and to a liipited extent iti fed cells. LD has wide tissue distribution, and is thus relatively nonspecific. ALP is found in a number of tissues, but in normal individuals primarEy reflects bone and liver sources. Thus based on tissue distribution, ALT and GGT would seem to be the most specific markers for liver injury. 

Prenylation also influences the balance between myocyte viability and apoptosis. Statin-induced apoptosis has been demonstrated in vitro, using myotubes [84], myoblasts [85], and differentiated primary human skeletal muscle cells [86], This effect can be reproduced by geranyl-geranyl-transferase inhibitors, and rescued by replacement of mevalonic acid [84], Compelling evidence suggests that statins cause apoptosis in skeletal muscle by disrupting the prenylation of small G proteins like Rho [85],... 

Some organs (e.g., heart and skeletal muscle) can use ketone bodies (/J-hydroxybutyrate and acetoacetate) as an energy source under normal conditions. During starvation the brain uses them as an important fuel source. Because liver does not have /J-oxoacid-CoA transferase, it cannot use ketone bodies as an energy source. These reactions are reversible. 

H62. Hussey, A. J., Kerr, L. A., Cronshaw, A. D., Harrison, D. J., and Hayes, J. D., Variation in the expression of mu-class glutathione S-transferase isoenzymes from human skeletal muscle Evidence for the existence of heterodimers. Biochem. J. 273, 323-332 (1991). 

Carnitine acetyl transferase 2 High level in skeletal muscle and heart to facilitate use of acetate as a fuel... 

As Otto Shape runs, his skeletal muscles increase their use of ATP and their rate of fuel oxidation. Fatty acid oxidation is accelerated by the increased rate of the electron transport chain. As ATP is used and AMP increases, an AMP-dependent protein kinase acts to facilitate fuel utilization and maintain ATP homeostasis. Phosphorylation of acetyl CoA carboxylase results in a decreased level of malonyl CoA and increased activity of carnitine palmitoyl CoA transferase I. At the same time, AMP-dependent protein kinase facilitates the recruitment of glucose transporters into the plasma membrane of skeletal muscle, thereby increasing the rate of glucose uptake. AMP and hormonal signals also increase the supply of glucose 6-P from glycogenoly-sis. Thus, his muscles are supplied with more fuel, and all the oxidative pathways are accelerated. 

Acetate is an excellent fuel for skeletal muscle. It is treated by the muscle as a very-short-chain fatty acid. It is activated to acetyl CoA in the cytosol and then transferred into the mitochondria via acetylcamitine transferase, an isozyme of carnitine palmitoyl transferase. Sources of acetate include the diet (vinegar is acetic acid) and acetate produced in the liver from alcohol metabolism. Certain commercial power bars for athletes contain acetate. 

Scholte, H.R. Jennekens, F.G. Bouvy, J.J. (1979) J. Neurol. Sci. 40, 39-51 Carnitine palmitoyltransferase II deficiency with normal carnitine palmitoyltransferase I in skeletal muscle and leukocytes. Meola, G. Bresolin, N. Rimoldi, M. Velicogna, M. Fortunate, F. Scarlato, G. (1987) J. Neural. 235, 74-79 Recessive carnitine palmitoyl transferase deficiency biochemical studies in tissue cultures and platelets. 

Carnitine serves as a cofactor for several enzymes, including carnitine translo-case and acyl carnitine transferases I and II, which are essential for the movement of activated long-chain fatty acids from the cytoplasm into the mitochondria (Figure 11.2). The translocation of fatty acids (FAs) is critical for the genaation of adenosine triphosphate (ATP) within skeletal muscle, via 3-oxidation. These activated FAs become esterified to acylcamitines with carnitine via camitine-acyl-transferase I (CAT I) in the outer mitochondrial membrane. Acylcamitines can easily permeate the membrane of the mitochondria and are translocated across the membrane by carnitine translocase. Carnitine s actions are not yet complete because the mitochondrion has two membranes to cross thus, through the action of CAT II, the acylcar-nitines are converted back to acyl-CoA and carnitine. Acyl-CoA can be used to generate ATP via 3-oxidation, Krebs cycle, and the electron transport chain. Carnitine is recycled to the cytoplasm for fumre use. 

Existence of ChAT (acetyl-CoA-choline O-acetyl-transferase, EC 2.3.1.6) in skeletal muscles is probably of neural origin, and its activity varies among skeletal muscles. ChAT activity can be altered by increased or decreased neuromuscular activity. It appears that neuromuscular activity exerts a regulatory influence on neuronal production of ChAT. Alterations in ChAT activity in response to variations in muscular activity represent changes in enz3une synthesis, although effects on catabolism of the enzyme or on exoplasmic transport... 

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