INH (C6H7N3O)

Chemical Structure of INH

INH is a hydrazide of isonicontinic acid. The pyradine ring and the hydrazine group are neccesary componants of its chemical structure

Mechanism of Action

The mechanism of action of INH in Myobacterium tuberculosis is not completely known. There are many ways in which INH biologically interacts with the bacteria and the primary effect has not been determined. Several studies however have been done to demonstrate the mechanism.

In 1966 Bekierkunst reported the interaction of nicotinamide-adenine dinucleotide (NAD) concentration and M. tuberculosis. INH was shown to incresae enzyme activity and Bekierkunst suggested that INH inactivates an inhibitor of NAD which enhances hydrolysis but no further studies have supported this conclusion.

Another study by Sriprakash and Ramakrishnan showed that INH increased the breakdown of NAD as well as decreasing its synthesis. This is described as the reason why M. tuberculosis accumulates much nicotinic acid. In 1977 however it was concluded that NAD depeletion was not neccesarily linked with the antituberculosis properties of INH.

In 1954 a scientist team Krueger- Thiemer proposed that the bactericidal effect of INH is caused by multiple effects by NAD analogs. Several studies supported this hypothesis later on.

Inhibition of mycolic acid synthesis is also associated with the mechanism of INH. In 1952 a researcher Middlebrook noted the loss of acid-fastness of M. tuberculosis when INH is present. INH decreases the synthesis of fatty acids with chain lengths longer than 16 carbons. Disbelievers of this hypothesis argue that it is hard to tell the direct effect of INH when no direct target can be named.

Lastly the role of mycobacterial catalase peroxidase has been observed in relation to INH. In 1954 Middlebrook also discovered that INH resistant strains of M. tuberculosis expressed little or no mycobacterial catalase peroxidase but the exact link between the two still remains unknown.

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