Creatine precursors

Arginine is the formamidine donor for creatine synthesis (Figure 31-6) and via ornithine to putrescine, spermine, and spermidine (Figure 31-3) Arginine is also the precursor of the intercellular signaling molecule ni-... 

FIGURE 22-26 Biosynthesis of creatine and phosphocreatine. Creatine is made from three amino acids glycine, arginine, and methionine. This pathway shows the versatility of amino acids as precursors of other nitrogenous biomolecules. 

Didanosine is a synthetic purine nucleoside analog that inhibits the activity of reverse transcriptase in HIV-1, HIV-2, other retroviruses and zidovudine-resistant strains. A nucleobase carrier helps transport it into the cell where it needs to be phosphorylated by 5 -nucleoiidase and inosine 5 -monophosphate phosphotransferase to didanosine S -monophosphate. Adenylosuccinate synthetase and adenylosuccinate lyase then convert didanosine 5 -monophosphate to dideoxyadenosine S -monophosphate, followed by its conversion to diphosphate by adenylate kinase and phosphoribosyl pyrophosphate synthetase, which is then phosphorylated by creatine kinase and phosphoribosyl pyrophosphate synthetase to dideoxyadenosine S -triphosphate, the active reverse transcriptase inhibitor. Dideoxyadenosine triphosphate inhibits the activity of HIV reverse transcriptase by competing with the natural substrate, deoxyadenosine triphosphate, and its incorporation into viral DNA causes termination of viral DNA chain elongation. It is 10-100-fold less potent than zidovudine in its antiviral activity, but is more active than zidovudine in nondividing and quiescent cells. At clinically relevant doses, it is not toxic to hematopoietic precursor cells or lymphocytes, and the resistance to the drug results from site-directed mutagenesis at codons 65 and 74 of viral reverse transcriptase. 

Uric acid is associated with urea, creatine and creatinine in urine. In the urine of mammals it occurs in small amounts, the chief nitrogen compound being urea. In birds and reptiles, however, uric acid predominates and is the precursor of the related guanine in guano. 

Reagent layer Buffer. pH 70, creatine phosphate, ADP, magnesium acetate, diadenosine penta-phosphate, glycerol, peroxidase, glycerol kinase, leuco dye precursor, L-a-glycero-phosphate oxidase, AMP, creatine phosphate ... 

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. 

In muscle, arginine is also involved as a precursor of creatine and creatine phosphate (Reaction 4 below). 

Arginine is a precursor to nitric oxide, a novel second messenger and neurotransmitter. The complex conversion of arginine to citmlline and nitric oxide is shown in Figure 21.3 as is the conversion of arginine to creatine phosphate. 

Fig. 19.7. Some compounds with high-energy bonds. 1,3-bisphosphoglycerate and phosphoenolpyruvate are intermediates of glycolysis. Creatine phosphate is a high-energy phosphate reservoir and shuttle in brain, muscle, and spermatozoa. Acetyl CoA is a precursor of the TCA cycle. The high-energy bonds are shown in blue.

S-adenosylmethionine (SAM) SAM, produced from methionine and adenosine triphosphate (ATP), transfers the methyl group to precursors forming a number of compounds, including creatine, phosphatidylcholine, epinephrine, melatonin, methylated nucleotides, and methylated DNA. 

The more complex sulphur requirements of the marine animals are met largely by cysteine, cystine, methionine, biotin, and thiamine (Young and Maw, 1958) (Fig. 4). Cysteine is a component of the tripeptide glutathione and a precursor of taurine. Methionine is as an essential amino acid involved in biosynthesis of proteins, creatine and adrenaline. Adenosylmethionine is considered to be the active part in transmethylation, e.g. of choline. Methionine is part of the pathways to homocysteine, cystathionine and methylthioadenosine (Young and Maw, 1958). Various organisms convert cysteine and/or cystine into mercapturic acids, cysteine sulphinic acid, and thiazolidine derivatives (Zobell, 1963). 

In addition to being synthesized or produced by the hydrolysis of dietary protein, amino acids are released by the hydrolysis of tissue proteins, e.g., intestinal mncosa and mnscle. Amino acids enter protein synthesis (Chap. 9) they also enter glnconeogenesis, lipogenesis, or are degraded to provide energy, as well as being used for synthesizing componnds such as purines, pyrimidines, and porphyrins. They are precursors of specialized metabolites such as epinephrine and creatine (Fig. 13-29). 

Jagerstad, M., Laser-Reutersward, A., Olsson, R., Grivas, S., Nyhammar, T., Olsson, K., and Dahlqvist, A. 1983a. Creatin(in)e and Maillard reaction products as precursors of mutagenic compounds Effects of various amino acids. Food Chem. 12 255-264. 

Arginine is the precursor of creatine, which combines with ATP to form creatine phosphate (Chapter 10). Creatine is excreted as creatinine. 

---