Side-chain cleavage SCC of cholesterol

Once cholesterol is transferred to the inner mitochondrial membrane of steroidogenic tissues such as adrenals, ovaries and testes, it encounters the enzyme system known as the cholesterol SCC system. This probably comprises 20- and 22-hydroxylases and a C-20,22-lyase, all tightly bound to the inner face of the membrane and associated with a specific cytochrome / -450scc. In addition, molecular 02 is necessary together with NADPH reductase and non-haem iron sulphur protein, which are called adrenodoxin reductase and adrenodoxin, respectively, in the adrenal [24] (Fig. 3). 

The nature of the C6 side-chain fragment produced depends, to some extent, on the tissue utilised and the conditions under which the experiments are carried out, but it is generally accepted that 4-methyl pentanal is formed first and that this may be oxidised to the corresponding acid or, alternatively, reduced to 4-methyl pen-tanol [29]. 

Despite suggestions that the side-chain of cholesterol may be cleaved completely in adrenal preparations [39,40], further work indicated that little or none of the C,y 

Finally, in this section, mention must be made of the specificity of the SCC reaction. C22 to C27 sterols, all with saturated side-chains, underwent cleavage in rat and bovine adrenals and porcine testis, at much the same rate as cholesterol itself however, sterols with polar side-chains, e.g. 24-, 25- or 26-hydroxycholesterol, were cleaved at higher rates [46]. The 5-cholesten-3/3-ol structure seems to be a necessary requirement for the substrate for SCC [47], but the more polar sterols may enter mitochondria more readily than cholesterol itself and bind to P-450scc which, in 

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