The Biochemistry of Creatine and Creatinine

Abstract: Publisher Summary This chapter focuses on physiological action of vitamin E and its homologues. Studies have shown that the ability of plants to prevent the symptoms of vitamin E deficiency in animals is due solely to the presence of three higher alcohols for which the common designation of tocopherol has been given. None of the other organic compounds known to possess vitamin E action is found in the plant world. The methods used for their isolation from natural sources involved extraction with fat solvents, saponification, partition of the nonsaponifiable fraction between solvents, removal of sterols with digitonin, chromatographic analysis, vacuum distillation, and isolation as crystalline allophanates or as other esters. Molecular distillation from vegetable oils is used extensively for the commercial production of the natural tocopherols; the synthetic forms are readily prepared in the commercial laboratory. In this chapter, nature of vitamin E is elaborated. Chemistry of the tocopherols is discussed. Structural and functional disturbances due to lack of vitamin E is described in detail. Interrelationships of vitamin E with other vitamins are discussed as well.

Abstract: Zinc, cadmium and mercury(II) complexes of creatinine of the composition M(Creat) 2 X 2 (X = Cl, Br or I) are prepared. The complexes are characterized by analytical and spectral methods. The increase in cyclic NH stretching frequency in the case of complexes (3350 cm −1 ) from that of the free ligand (3300 cm −1 ) suggested that secondary nitrogen is involved in coordination. The shift in the resonances of cyclic NH proton in the 1 H NMR and carbonyl and imine carbons in 13 C NMR when compared to the ligand indicated that cyclic nitrogen coordinates. Conductivity measurements in N, N-dimethylformamide suggested that the complexes are non-electrolytes. Thermal decomposition behaviour of the complexes is also discussed.

Abstract: Cobalt(II) complexes of creatinine [Co(creat)2X2] (X = Cl, Br, I or NCS) and [Co(creat)2X2(H2O)2] (X = HCO2, HOCH2CO2 or CNCH2CO2) have been prepared. Their i.r. spectra show an increase in ν(NH) of the cyclic secondary amine group, compared to free ligand (3300 cm−1), indicating that cyclic nitrogen is involved in coordination. The thiocyanate group coordinates through nitrogen and carboxylates coordinate as univalent unidentate ligands. The electronic spectra and magnetic moments suggest a d7 configuration for cobalt: a tetrahedral geometry (4.4 B.M.) for halide and thiocyanate complexes, and an octahedral geometry (5.0 B.M.) for the carboxylate complexes. On heating, the ligand moiety is lost and the respective cobalt halide or cobalt carboxylate is formed, which is converted finally into Co3O4. There is a correlation between the high intensity electronic transitions and the polarographic half-wave potentials.

Abstract: It is generally accepted that creatinine produced by endogenous metabolism is derived from muscle creatine and phosphocreatine. The conversion is apparently the result of an irreversible process of normal metabolism which takes place at a constant rate, proportional to muscle mass and independent of muscular exercise.* The daily urinary excretion of creatinine is constant for the individual, ranging from 1.5 to 2.0 gm. for men and from 0.8 to 1.5 gm. for women. This corresponds to approximately 2% of the total body creatine, from which it is derived. This excretion rate is apparently independent of protein ingestion and is considered an index of muscle metabolism. It is not influenced by exercise or urine volume. Decreased creatinine excretion, with concurrent elevation in plasma level, is generally indicative of impaired renal function, since creatinine is freely filterable at the glomerulus. Decreased excretion in the absence of elevated plasma concentration is usually due

Abstract: Negative feedback systems are believed to be operative in higher animals in physiologically important processes ranging from formation of tropic hormones to maintenance of organ size. However, model systems for the study of such controls at the molecular level in intact animals are quite rare, and are limited to two biosynthetic pathways: the cholesterol-bile acid pathway, and the creatine pathway. In this paper the properties of the latter model system are described in detail. Two enzymes are involved in the biosynthesis of creatine. The second enzyme appears to be constitutive, whereas the steady-state level of the first enzyme, arginine-glycine transamidinase, is responsive to the tissue concentration of creatine. This process has been operationally termed end-product repression, by analogy with bacterial systems, until its mechanism can be more completely elucidated. Creatine repression of transamidinase has been observed in the rat, mouse, rabbit, chick, and duck, in tissues as diverse as kidney, pancreas, and liver. More recently, repression has been studied in the liver of the developing chick embryo and the newly hatched chick. Virtually complete repression of embryonic liver transamidinase can be maintained throughout development by a single injection of creatine into the egg. Derepression occurs in the first week following birth, when chicks are fed a normal diet. Numerous experiments have shown that there is a highly specific relationship between the target enzyme and the controlling compound. Creatine precursors proximal to the target enzyme repress 35–50 per cent while the precursor distal to the target enzyme represses completely. In the closed system of the egg, repression of the target enzyme can be readily shown to be proportional to repressor concentration. Moreover, this system permits the demonstration that repression can occur in the absence of intestinal flora, and under conditions of minimal hormonal influences. The normal pattern of change of transamidinase activity during embryonic and neonatal development is consistent with a repression by endogenous creatine prior to birth, followed by a post-hatch derepression, but other explanations are also entertained. Evidence is cited in support of the thesis that the creatine-transamidinase control system has survival value for birds, and perhaps reptiles and amphibians. It is suggested that liver transamidinase of carnivorous birds is normally in a partially repressed state, as a result of the 0·4 per cent creatine content of ingested muscle tissue, whereas transamidinase of herbivorous birds is normally derepressed. Experimentally it has been demonstrated that fasting lowers the activity of both the repressed and derepressed enzymes. At least part of this decrease can be attributed to a repression by endogenous creatine which appears in increased concentration in the blood, liver and kidneys of most higher animals during fasting. During fasting, then, the decrease in transamidinase activity permits diversion of a portion of the dietary essential amino acids, arginine, glycine, and methionine, from the synthesis of creatine, now in excess, to more immediately essential biosyntheses. For example, glycine is essential for synthesis of the uric acid required to remove amino groups arising from the gluconeogenesis of fasting; methionine methyl groups are required for the increased lipid transport of fasting; and all three amino acids are needed for synthesis of essential enzymes, protein hormones, and feathers. In addition to the foregoing, the implications of the occurrence of a repressible system during embryonic development for the problem of the establishment and maintenance of tissue-specific enzyme levels are discussed.