Metabolic pathways creatine

After sulfide is oxidized to sulfate (the major metabolic pathway), sulfate is excreted in the urine (Beauchamp et al. 1984). A human volunteer exposed at a concentration of 18 ppm hydrogen sulfide for 30 min was found to have urinary thiosulfate concentrations of approximately 2, 4, 7, 30, and 5 /nnol/mM creatine 1, 2, 5, 15, and 17 h after exposure, respectively (Kangas and Savolainen 1987). Blood thiosulfate concentrations decreased in rabbits exposed to hydrogen sulfide at a concentration 100-200 ppm for 60 min from 0.061 /tmol/mL immediately after exposure to an undetectable amount after 4 h (Kage et al. 1992). Urine... 

Figure 14.7. Sources of ATP During Exercise. In the initial seconds, exercise is powered by existing high phosphoryl transfer compounds (ATP and creatine phosphate). Subsequently, the ATP must be regenerated by metabolic pathways.

Even though AMP-induced activation of glycolysis and glycogenolysis is rapid, cellular reserves of ATP would only allow vigorous contraction of skeletal muscle for 1 s. An instantly available store of high-energy phosphate is provided by creatine phosphate. Creatine kinase is exceptionally active and maintains the reaction between creatine and ATP, and creatine phosphate and ADP, in rapid dynamic equilibriiun. This pool of creatine phosphate serves as a buffer for ATP that occurs without any activation of metabolic pathways. 

Creatine is synthesized in an interorgan metabolic pathway that spans the kidney and liver. In the kidney, arginine and glycine are condensed to form guanidinoacetate, which is exported from the kidney and taken up by hepatocytes in which it is methylated. Creatine phosphate is chemically rmstable and spontaneously cyclizes to give creatinine and phosphate it cannot be reverted back to creatine, so it is a metabolic end product that is excreted in the urine. Because the size of the creatine phosphate pool is relatively constant, the amount of creatinine produced in 24 h is also relatively constant. Thus, the amoruit of creatinine excreted in the urine is used clinically to gauge renal excretory function. 

Several metabolic pathways (e.g. hpid metabohsm, creatine and carnitine synthesis) require methyl groups and these can be snppUed by choline or methionine. During the process of transmethylation, betaine, a tertiary amine, is formed by the oxidation of choline. Betaine can be added to the diet to act as a more direct supply of methyl groups, thus sparing choUne for its other fimctions of lecithin and acetylcholine formation, and methionine for protein synthesis. Betaine occurs in sugar beet. 

Fig. 24.1. Metabolic pathway of creatine/creatine-phosphate. AGAT, arginine glycine amidinotransferase GAMT, guanidinoacetate methyltransferase CRTR, creatine transporter CK, creatine kinase...

During the recovery period from exercise, ATP (newly produced by way of oxidative phosphorylation) is needed to replace the creatine phosphate reserves — a process that may be completed within a few minutes. Next, the lactic acid produced during glycolysis must be metabolized. In the muscle, lactic acid is converted into pyruvic acid, some of which is then used as a substrate in the oxidative phosphorylation pathway to produce ATP. The remainder of the pyruvic acid is converted into glucose in the liver that is then stored in the form of glycogen in the liver and skeletal muscles. These later metabolic processes require several hours for completion. 

Skeletal muscles use many fuels to generate ATP. The most abundant immediate source of ATP is creatine phosphate. ATP also can be generated from glycogen stores either anaerobically (generating lactate) or aerobically, in which case pyruvate is converted to acetyl CoA for oxidation via the TCA cycle. All human skeletal muscles have some mitochondria and thus are capable of fatty acid and ketone body oxidation. Skeletal muscles are also capable of completely oxidizing the carbon skeletons of alanine, aspartate, glutamate, valine, leucine, and isoleucine, but not other amino acids. Each of these fuel oxidation pathways plays a somewhat unique role in skeletal muscle metabolism. 

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