Conjugation Of Benzoic Acid Research Articles

Influence of Ortho-Substitution on the Conjugation of Benzoic Acid

Substitution of benzoic acid in ortho position almost completely inhibits in the dog the conjugation with glycine. The effect appears to be independent of the nature of the group, for the methyl, chloro, bromo, iodo, nitro, and hydroxyl radicals impede the union with glycine. Substitution in meta and para position, on the other hand, exerts no steric hindrance. The conjugation of benzoic acid with glycuronic acid is also affected by substitution in ortho position, but the nature of the substituting group is of fundamental importance. Taking the conjugation of benzoic acid as standard, it was found that a neutral group such as the methyl exerted no effect; an acid group like the chloro or the hydroxy caused a definite decrease in the excretion of the glycuronic acid compound; a strongly acid group such as the nitro suppressed the excretion almost completely; whereas a basic group like the amino produced a marked increased output of the glycuronic acid compound. Excretion of uncombined acid was observed only when a strongly acidic group occupied the ortho position. The various compounds were neutralized with sodium hydroxide and mixed with a glycine free diet. The equivalent of 3 gm. of benzoic acid was fed. In the case of o-iodo-benzoic acid only half that amount was given. The importance of these considerations from the point of view of correlating pharmacological action with chemical structure is illustrated by salicylic acid, a compound containing the acidic hydroxy radical in ortho position to the carboxyl group. The importance of these considerations from the point of view of correlating pharmacological action with chemical structure is illustrated by salicylic acid, a con~pound containing the acidic hydroxy radical in ortho position to the carbosyl group.

The conjugation of benzoic acid in rabbits.

A study has been made of the excretion of free benzoic acid, hippuric acid, and total combined benzoic acid in the urine of normal adult rabbits following the administration of sodium benzoate. The maximum rate of synthesis of hippuric acid occurred after the ingestion of 0.5 gm. of benzoic acid per kilo. Larger doses of benzoic acid increased the rate of excretion of combined benzoic acid but not that of hippuric acid. In the 24 hour period following the administration of 1.0 gm. of benzoic acid per kilo, the average excretion of hippuric acid in six rabbits was 82 per cent of the combined benzoic acid, the individual variations ranging from 65 to 90 per cent. These urines contained an ether-soluble, non-fermentable reducing substance which gave a positive naphtho-resorcin test. Therefore, it was concluded that 10 to 35 per cent of the combined benzoic acid excreted by the six rabbits was benzoyl glycuronic acid. It has long been known that the rabbit excreted benzoyl glycuronic acid following benzoate a...

MECHANISM OF THE REACTION BETWEEN BILE SALTS AND BLOOD SERUM AND THE EFFECT OF CONJUGATION IN THE FORMATION OF BILE SALTS

THESE EXPERIMENTS SUGGEST THE FOLLOWING CONCLUSIONS CONCERNING HEMOLYTIC ACTION: 1. It is probably the proteid part of the serum which inhibits the bile salts. 2. The cholalic acid group is the active part of the bile salt molecule. 3. The protection afforded by bile salts against serum is of especial interest from the following considerations: (a) The protective action is a property apparently peculiar to proteids obtained from blood serum. It is not given satisfactorily by egg albumen. (b) The conjugation of cholalic acid with glycocoll in the formation of the bile salts is of some advantage to the organism. Although the toxicity of the cholalate for red corpuscles, when free from serum, is at most only slightly diminished by conjugation, yet the blood serum possesses a greater inhibiting action for the resulting glycocholate than for the original cholalate. 4. As compared with its inhibition of sodium glycocholate, normal serum possesses relatively little inhibiting action against certain foreign hemolytic agents, such as tetanus toxin, sodium benzoate, phenol and ethyl alcohol. 5. Hemolytic experiments afford a fairly general method for studying, in vitro, certain syntheses occurring in the body. They avoid, largely, the complications, such as rapid chemical alteration, which might occur in animal experimentation. Contrary to the results obtained with bile salts, the conjugation of benzoic acid and of phenol results in an effective reduction of their hemolytic action independently of the presence or absence of serum.