THE ROLE OF DISULPHIDES AND MERCAPTANS IN HAIR CHEMISTRY By J. L. STOVES, ProD., M.Sc., F.R.I.C.* ArAsT from a small amount Of methionine, the whole of the sulphur present in keratin fibres can be accounted for as cystine, the dis- position of this amino-acid within the fibre being such as to form a bridge between peptide chains: CH.CH2.S.S.CH2.CH Many estimations of the sulphur content of keratin fibres have been made and it is now definitely estab- lished that different animal fibres contain varying amounts of sulphur. Neglecting differences due to histo- logical variations, the significance of which has been discussed else- where,',' variation in the sulphur content of hair from the same species is now regarded simply as indicating variation in the number of cystinc disulphide'linkages between the peptide chains. An argument against the presence of such linkages in keratin has been based on the fact that chemical reactivity of protein sulphur is much greater than that of sulphur in free cystine. As already indicated? however, this increased reactivity of protein sulphur can be readily understood in view of the nature of the groupings attached to the cystine linkage in hair. * Chemical Consultant. 170 CYSTINE AND HAIR GR0W•H Since keratin contains a relatively high percentage of cystine .(c. 15 per cent in human hair) it has been : suggested, from time to time, that"/i hair growth would be stimulated by supplying to the diet preparation'sil/il rich in sulphur and cystine. Very:i f i conflicting results have been obtained when this form of therapy has been applied to human beings. Difficul- •.! ties of experimental technique the fact that cystinc or sulphur'•(• deficiency is only one of several•:i • possible causes of poor hair growth-i goes far to explain these variables: results. In the cosmetic field interesC!: has long centred round the possibilit71'i of stimulating hair growth by exter•: nM application of the essential con.-: stituents of keratin. Recent work•i:i• on cutaneous absorption, e.g.,Valett• in Paris, Hermann, Su!zberger Baer in U.S.A., has shown that unde• • t ,, certain conditions' penetrasols based on propylene glycol, xylol, an hydr02:i! tropic substance like antipyrine a wetting agent of the sodium ary alkyl sulphonate types possible to convey the most vari'•d! substances through the epiderm!•: Penetration in all cases takes pla6 via the hair follicles, passage throug]

DISULPHIDES AND MERCAPTANS IN HAIR CHEMISTRY "•c/)•?the walls of which occurs in the below the level of the kera- tinised layer. i,•:•!i.'i•:::... Colloidal sulphur dissolved in oil is ?!:another substance which is readily '??:!ii :absorbed, liposolubility being i?:):?i'essential for penetration of substances i!•11through the layer of s&bum lining :ii.i:.iithe hair follicle. ?•:!i:•':•'!:i'::•:':So far as penetration of .hair ß •::•::::-:½ nuthen s •s concerned, therefore, ':-:•:•:i•('i!!ithis work opens up,an interesting ?:!field for investigation. There still :!i!:. .i',remains the question of assimilation ?:0f penetrants by the hair papilla, ili:i::'and here in particular there is room :!117: 'for str/ctly' controlled-experiment, : ?!!::Possibly using radioactive isotopic '•?11:!markers. In this connection labora- (ii •: ?tory experiments• have already !•,?:::'shown that methionine can replace ,i. ! ::(!:•the dietary cystine necessary for :i?growth of •he rat, and can provide :!?':. !.•he sulphur which appears as cystthe :}! !::"in keratin? Toennies* suggested that conversion of methionine to cystine .i.!?i ' Probably proceeds through the form- ii::.: i etlon of a methyl sulphonium derive- i -'::::: •ive of S-([•-amino-[t-carboxyethyl)- .i:i/:/:(homocystine by direct. coupling of ':'•' methionine with serine. ': This methyl •:: •-:'::' sulphonium derivative, by elimina- :::.? •.tion. of methyl alcohol. and subse- ' *, : :'quent cleavage would y/eld cysteine. ?:: i": The.unsymmetrical thio-ether cysta- :?: thionine which is the second stage in ::::'. the Toennies mechanism, was pre- !?:':pared by Brown and du Vigneaud' ß i::: and shown to be split in vivo pre- ::::.:.: ferentially to cysteine. The follow- ,, ß ing year cysteine was also :shown to be formed when homocysteine and serine were added in vitro to liver slices under anaerobic conditions, and the isolation by Stettin of cysteine containing a high concen- tration of nitrogen isotope from the tissues of rats fed on serine containing N" added farther confirmation to the theory. Kilmer 'and du Vig- neaud' later prepared dl-methionine containing an excess of the. stable isotopes S •' and C", the latter in the [• and •, positions. When this was fed to rats the isotopic ratios in the cystine isolated from •he fur indi- cated 'that 80 per cent approxim- ately of .the sulphur, but no signifi- cant amount of carbon from the methionine found' its way into the cystine. This observed transfer of sulphur agreed with the previous demonstration' using radioactive S '•, and it appears, therefore, -that methionine provides its sulphur, but none of its carbon for the synthesis of cystine in vivo. So far as the f. ormulation of hair dressings and brilliantines is con- cerned it is true to say that more precise information on cutaneous absorption and assimilation of amino- acids and sulphur 'compounds in normal and pathological scalp con- ditions is desirable. Nevertheless, at the present time the incorporation of keratin hydrolysates, methionine or• colloidal sulphur in such lotions seems to be' amply justified on empirical grounds. The cystine disulphide linkages of hair appear to be formed mainly during the process of keratinisation. Throughout the lower regions of the hair follicle where the fibre is actively growing, cortical cells are 171