Inosinic acid, muscle

Hypoxanthine, 9 -(5-phospho-D-ribofur-anosyl)-. See Inosinic acid (muscle). 

The existence of two separate enzymes in animal tissues responsible for the liberation of ammonia from each of the two aminopurines, adenine and guanine, the latter specific for the free purine and the former for the nucleosides, was initially presented by Jones and his colleagues 11, 12). In 1928, Schmidt 13-15) demonstrated that AMP aminohy-drolase was responsible for the appearance of inosinic acid in muscle and for at least a portion of ammonia liberated during contraction. He showed not only a marked specificity for deamination of 5 -AMP but also provided the first clue that muscle adenylic acid (5 -AMP) and yeast adenylic acid (3 -AMP) were different compounds. Initial evidence for guanine and adenosine aminohydrolase including aspects of the specificity were also described by Schmidt 16). Additional details regarding development of interest in purine aminohydrolases are available in several excellent reviews 17-20). 

Historically, this method of stepwise hydrolysis seems to have been first applied to a nucleotide by Levene and Jacobs, in determining the structure of muscle inosinic acid. ... 

On phosphorylation of isopropylidene-inosine, followed by hydrolysis of the acetone residue, muscle inosinic acid (which, as will be seen later, is definitely known to be 5-phospho-inosine) is formed. This confirms the above formulations for isopropylidene-inosine and inosine. 

Finally, muscle inosinic acid itself was synthesized by Levene and Tipson. This was the first (partial) synthesis of a naturally occurring nucleotide. Phosphorylation of 2,3-isopropylidene-inosine, the structure of which has already been discussed, gave the corresponding 5-phospho derivative, from which the isopropylidene group was cautiously hydrolyzed, yielding 5-phosphoinosine which proved to be identical with muscle inosinic acid. 

Inosinic acid (1), the first nucleotide to be discovered, was isolated over a century ago from beef extract by Liebig. Mild, acid hydrolysis of this nucleotide yielded a ribose phosphate (2) which, by oxidation with nitric acid, gave a ribonic acid phosphate (3), but not a ribaric acid phosphate. These studies by Levene and his associates showed that the phosphoric (phospho) group is bound to the 5-hydroxyl group of the ribosyl moiety in 1 hence, inosinic acid is inosine 5 -phosphate. Adenylic acid (4), isolated from muscle, was converted enzymically (by adenylic... 

Inosinic Acid, 5 -Inosinic acid 5-tnosimc acid muscle inosinic acid t-inosinic acid hypoxanthine ribosjde-5-phosphoric acid IMP. C.jH.jNjOjP mol wt 348.22. C 34.49%, H 3,76%, N 16.09%, O 36,76%, P 8,90%. Prepn from meat extract Levene, Bass, Nucleic Acids (New York, 1931) p 229 from dried sardines Yoshida, Kageyama,... 

GB started commercial manufacture of white P from bones Concluded phosphate of lime was the important nutrient in bones Condensed polyphosphoric acids prepared P-containing Lecithin first isolated from egg yolk Phosphate rock first mined in Suffolk, England Discovered thiophosphoric esta-s Inosinic acid isolated from beef muscle Existence of trimethylphosphine, PMe, reported First preparation of red phosphorus... 

In 1925, the structure of inosinic acid, which was thought to be the 5 -monophosphate of inosine, was confirmed. Inosinic acid, the first free nucleotide to be recognized, has an interesting history (4). In 1847, the barium salt of this substance was isolated from beef extract by Leibig, who derived the name from the Greek words for muscle fiber. The presence of phosphorus in this substance was not recognized until 1895. In 1909, Levene determined the structure of inosine, a hydrolysis product of inosinic acid, to be the riboside of hypoxanthine with this information, the nucleotide structure of inosinic acid became apparent. 

An important discovery, that of free adenylic acid in muscle, was made by Embden in 1927. Muscle adenylate was recognized as the 5 -mono-phosphoric ester of adenosine because enzymatic deamination yielded the known inosinic acid. It was shown at that time that the deaminase preparations from muscle did not deaminate the adenylic acid isolated from alkaline hydrolysates of yeast nucleic acid as well, differences were apparent in the chemical properties of the adenylic acids from these two sources. Yeast adenylic acid and the other nucleotides from alkaline hydrolysates of RNA were ultimately shown to be mixtures of the 2 - and 3 -phospho esters. In 1929 the isolation of adenosine triphosphate from muscle was reported by Lohmann and independently by Fiske and Subbarow. The discovery of adenosine diphosphate followed in 1935. 

The 5 -adenyhc acid deaminase (22) found in rabbit muscle has been crystallized (23). It converts adenylic acid to inosinic acid and ammonia [Eq. (7)]. The enzyme does not deaminate adenine, adenosine, adenosine diphosphate, adenosine triphosphate, adenosine 2 -phosphate, adenosine S -phosphate, guanosine, or cytosine but does act upon deoxyadenylic acid (24)-... 

Adenylic acid, now called muscle adenylic acid to distinguish it from adenylic acid obtained from yeast, is widely distributed in animal tissue, and ranks along with histamine and acetyl choline as a powerful vaso-dilator. On deamination it is converted to the much less active inosinic acid. Adenylic diphosphate (or pyrophosphate) is found in muscle where it acts as a donator of phosphoric acid in the contraction process (p. 291), becoming degraded to adenyl phosphate durii the change. 

Japan, pat. 732C86) (to Ajinomoto), C.A. 51, 3870b (1957). Structure Levene, Bess, op. ctt.. pp 187-192 Bredereck, Ber. 66, 198 (1933) Levene, Tipson, J. Biol. Chem. Ill, 3t3 (1935). Also prepd from muscle by enzymatic deamination of muscle adenylic acid Ostem, Biochem. Z. 254, 63 (1932) by hydrolysis of inosine triphosphate Kleinzeller, Biochem. J. 36, 729 (1942). Studies on the enzymatic synthesis Greenberg, J. Biol. Chem. 198, 611 (1951) Korn et al, ibid 217, 875 (1955). Microbial fermentation method using mutant strains of Micrococcus glutamicus Kinoshita el al. U.S. pat. 3,232,844 (1966 to Kyowa). 

Pentose phosphates occur naturally in the nucleic acids, each of which is made up of four mononucleotides, or glycosides of pentose monophosphate (p. 130). 5-phosphoribose occurs in the nucleic acid of animal chromatin, and in the inosinic and adenylic acid of muscle (p. 291). 3-phosphoribose occurs in the guanylic acid, xanthylic acid and nucleic acid found in yeast (p. 348). 

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