Creatine, biosynthesis

Creatinine is formed in muscle from creatine phosphate by irreversible, nonenzymatic dehydration and loss of phosphate (Figure 31-6). The 24-hour urinary excretion of creatinine is proportionate to muscle mass. Glycine, arginine, and methionine all participate in creatine biosynthesis. Synthesis of creatine is completed by methylation of guanidoacetate by S-adenosylmethio-nine (Figure 31-6). 

Arginine serves as the formamidine donor for creatine biosynthesis, participates in polyamine biosynthesis, and provides the nitrogen of nitric oxide (NO). 

T. Nakashima, M. Tomi, M. Tachikawa, M. Watanabe, T. Terasaki, and K. Hosoya. Evidence for creatine biosynthesis in Muller glia. Glia 52 47-52 (2005). 

Muscle activity involves processes such as aerobic and anaerobic glycolysis and is therefore accompanied by an increased pyruvate production. Consequently, the pyruvate transamination product alanine will be increased after exercise. Heavy exercise may be associated with an increased need of creatine biosynthesis from arginine. Ornithine is a by-product of this pathway and may be increased under these conditions. 

Salomons GS, Johnston K, Plawner L, Cooper L, Barkovich J, Verhoeven NM, Jakobs C (2005) The second family with AGAT deficiency (creatine biosynthesis defect) diagnosis, treatment and the first prenatal diagnosis. J Inherit Metab Dis 28 224... 

Verhoeven NM, Salomons GS, Jakobs C (2005) Faboratory diagnosis of defects of creatine biosynthesis and transport. Clin Chim Acta 361 1-9... 

Pathway of creatine biosynthesis. In GMT deficiency, precursor guanidinoacetate accumulates and the synthesis of creatine and phosphocreatine is severely reduced. Creatinine, a nonmetabolizable end product that is excreted by the renal system, is also diminished. 

Williams, M., Dietary supplements and sports performance Aminoacids, Int, J, Sport Nutr., 2, 63, 2005. Walker, J.B., Creatine Biosynthesis, regulation and function, Adv. Enzymol. Relat. Areas. Mol. Med., 50, 177, 1979. 

Creatine biosynthesis defects Lysosomal cystine transport def., infantile Lysosomal cystine transport def, adolescent Hyperoxaluria type 1 Malonyl-CoA decarboxylase def Lysosomal cystine transport def, infantile Lysosomal cystine transport def, adolescent... 

Fig. 24.2. Diagnostic flow chart for the patient with creatine biosynthesis and cellular creatine transporter defect. Starting points are clinical symptoms and/or finding of I MRS brain creatine/creatinephosphate...

Walker JB. Creatine Biosynthesis, regulation, and function. Adv Enzymol 1979 50 177-242... 

Stockier, S. and E Hanefeld, Guanidinoacetate methyl transferase deficiency a newly recognized inborn error of creatine biosynthesis. Wiener Klinische Wochenschrift, 109 86-88, 1997. 

ARG is a precursor for creatine synthesis. In a 1976 study, ARG with glycine in equimolar amounts increased the rate of creatine biosynthesis. Based on the availability and success of creatine supplementation, there appears to be no sport application for the use of supplemental ARG as a substrate for creatine synthesis. 

Humm A, Fritsche E, Steinbacher S, Huber R. Crystal structure and mechanism of human L-arginine glycine ami dinotransferase a mitochondrial enzyme involved in creatine biosynthesis. EMBO J 1997 16 3373-3385. 

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