Inhibitors of oxidative degradation of protein: Gerotological implications

Abstract

Compounds were studied that inhibit the oxidative degradation of human serum albumin by peroxidase and the enzyme model, iron hydroxide. Differences between the two oxidants gave clues for the mechanism of inhibition. The inhibitors studied were inorganic anions, phosphate, sulfate, carbonate and molybdate; organic anions, decanoate and glycocholate; and the nonionic species, glycogen. Such inhibitors might be considered as adjuvants in senscence: by decreasing the rate of enzymic oxidation of essential body proteins, they would, in the course of aging, reduce some of the physiological changes occurring as a result of accumulation of degraded protein.

Oxidation of essential body constituents with subsequent accumulation of degraded oxidation products has been implicated as a factor in senescence by several authors (1). As an example, lipofuscin, found in old tissues, is possibly such a product, since hyperoxia increases its amount (2). In keeping with such considerations the present author has shown that human serum proteins are being oxidized by ubiquitous oxidizing enzymes, such as polyphenol oxidase (PPO) and peroxidase (PO) (3), and that undesirable oxidation products might accumulate in the tissues when the rate of synthesis of native proteins is reduced as is the case in advanced age (4).

It was accordingly thought desirable to establish what chemicals inhibit, at least partially, the activity of the enzymes mentioned. Such inhibitors, if normally present in the body, migh possibly counteract the oxidative degradation of tissues. Others, foreign to the body, might, if nontoxic, ultimately be considered as pharmaceuticals that could alleviate some of the symptoms developing as a result of accumulation of degraded oxidation products. The present study has been carried out with the aim of finding such inhibitors of protein oxidation.

The author also found that iron hydroxide sol is a suitable model for PO, since the latter carries an iron atom as an essential constituent. In the present study therefore parallel measurements of inhibition were carried out with both PO and iron hydroxide. Such parallel study was helpful in choosing possible candidates for inhibitor, as also in drawing some conclusions as to the possible mechanism of inhibition.