Our studies in the sixties from the Middle East established that zinc was an essential element for human growth and that zinc deficiency occurred in the human. Although we knew that carbonic anhydrase, alcohol dehydrogenase and carboxypeptidase were zinc metalloenzymes, it was not known if zinc deficiency would affect adversely the activation of any of the known zinc metalloenzymes. Most biochemists argued that we should not expect to see any adverse effect in the activities of the zinc metalloenzymes due to deficiency of zinc, in as much as the amount of zinc present in these enzymes was so small that tissues would not give up zinc in the enzymes due to deficiency as long as the animals were living. In these two papers we showed that this commonly held belief was not correct and that indeed as a result of zinc deficiency in rats in zinc sensitive tissues, the activities of several zinc metalloenzymes were adversely affected. In another study we showed that the activity of deoxythymidine kinase (TK), an essential enzyme for DNA synthesis in S phase and cell division was affected adversely in rapidly regenerating tissue as a result of zinc deficiency and this resulted in decreased growth. We hypothesized that this may be an important mechanism of zinc action on growth in animals and human.
Prasad, A.S., Oberleas, D., Wolf, P.L., Horwitz, J.P. Studies on zinc deficiency: Changes in trace elements and enzyme activities in tissues of zinc‑deficient rats. J. Clin. Invest., 46:549‑557, 1967.
Prasad, A.S., Beck, F.W.J., Endre, L. Handschu, W., KuKuruga, M., Kumar, G. Zinc deficiency affects cell cycle and deoxythymidine kinase (TK) gene expression in HUT-78 cells. J. Lab. Clin. Med., 128:51-60, 1996.