July 21, 192 ij 



NATURE 



665 



mono-amino-acids. Gelatin lacks cystine, tyrosine, 

 and tryptophan. Hair is richest in cystine. These 

 are simply some of the most obvious differences. 

 Proteins thus differ markedly in quality. 



Our analytical data are far from complete ; in no 

 case do the totals of the amino-acids add up to loo. 

 The incompleteness is chiefly due to the great diffi- 

 culty of separating and estimating the individual 

 amino-acids. There may be still some unknown 

 amino-acids in small quantities ; e.g. hydroxy-glutamic 

 acid has been discovered recently by Dakin by a new 

 extraction method. This method may yet lead to 

 new results ; once again it has proved that every 

 new process in connection with the chemistry of the 

 proteins has given a valuable result. 



Rather too great stress has been laid upon the 

 analytical figures. The methods scarcely give exact- 

 ness as far as the decimal figure, and it would have 

 been better if the data had been returned to the 

 nearest whole number. Many workers still give their 

 data to two places of decimals, so that an entirely 

 wrong impression is given of the accuracy of the 

 method. Fischer pointed out that his method was 

 not quantitative, but others have neglected this 

 important statement. 



The figures for the hexone bases are more accurate, 

 but it is still not sufficient to express results to two 

 decimal places. Kossel considers that the hexone 

 bases form a special nucleus on account of their 

 presence in all proteins. We might value a protein 

 bv its content of hexone bases, but it is not sufficient, 

 because their total only tells us about a third or less 

 of the whole molecule. 



Tryptophan, discovered by Hopkins and Cole, is 

 perhaps the most important unit in the protein mole- 

 cule. It is not estimated except by direct isolation — 

 a method which is laborious and requires considerable 

 skill. Its amount is not known except in casein and 

 a few other proteins. By its distinctive colour re- 

 action with glyoxvlic and sulphuric acids it can 

 readilv be proved to be a constituent of most proteins. 



The amount of cystine in proteins is Iftiown only in 

 a few cases, but its amount can be gauged by the 

 sulphur content of the protein. It is the one unit 

 known which contains sulphur, but there are indica- 

 tions that there is another sulphur-containing unit. 



The differences in proteins are not confined to such 

 quantitative data ; they are still more involved. Fischer's 

 synthetical work with the amino-acids has proved that 

 the amino-acids are combined together in a polv- 

 ppptide form, i.e. the amino-group of one amino-acid 

 is combined with the carboxyl group of another, the 

 amino-group of this acid being united with the carb- 

 oxyl group of still another. We therefore consider 

 a protein molecule to be a chain of amino-acids, thus : 



H,N-CH,-CO— NH-CH(CH,)-CO— 



NH-CH(C,H,)-CO— NH-CH(C,H,)-CO— 



This method of combination allows theoretically of 

 endless variation. If we take three amino-acids we 

 can arrange them in six different wavs : Glvcyl- 

 alanyityrosine, glycyltyrosvlalanine, alanylglycyltyro- 

 sine, alanyltyrosylglycine, tyrosylglycylalanine, and 

 tyrosylalanylglvcine. With eighteen or twentv amino- 

 acids the number of arrangements is almost infinite. 



Differences in arrangement may be the cause of 

 differences in proteins. Two proteins mav perhaps 

 have exactly similar amounts of amino-acids and vet 

 be different; a difference could be expressed bv the 

 interchange of one amino-acid. We mav imagine the 

 proteins of the blood or milk of different species to 

 differ thus : one may have the arrangement a, h, c, 

 d, e, f, the other d, a, h, f, e, c. 



Another important difference may exist in the so- 



NO. 2699, VOL. 107] 



called tautomerism of the amino-acids and poly- 

 peptides. With the same arrangement of the amino- 

 acids we may have several formulae representing the 

 polypeptide structure. Certain of the properties of 

 the polypeptides can be explained on this basis. 



Fischer and Kossel have revolutionised our concep- 

 tion of protein nutrition. We no longer think, like 

 Liebig and others, that the protein of the food becomes 

 directly the protein of the body, for it has been demon- 

 strated by the physiologists that the protein of the 

 food undergoes hydrolysis during digestion to amino- 

 acids, that the amino-acids circulate in the blood, and 

 that the tissues receive amino-acids from which they 

 build up their protein. Proteins must be regarded as 

 a mixture of amino-acids. 



We can look upon a protein as we look upon the 

 contents of a box of assorted biscuits, arranged in 

 rows and layers of various kinds. Each biscuit should 

 be connected to its neighbour so that we have a con- 

 tinuous chain. The general appearance of the con- 

 tents of two boxes is different ; in one case we may 

 find sugary biscuits on the top, in another plain 

 ones. In the process of digestion the protein is acted 

 upon by acid in the stomach with the formation of 

 metaprotein. No great chemical change occurs, but 

 we can imagine that the change consists in a tauto- 

 meric re-arrangement in preparation for the action 

 of pepsin. Pepsin hydrolyses the protein at certain 

 junctions, forming proteoses and peptones. Their 

 formation can be compared with the separation of 

 the layers of the biscuits. Pancreatic and the further 

 digestion which follow in the intestine separate the 

 individual amino-acids or biscuits entirely. The 

 separate parts circulate to the tissues ; the tissues 

 select the ones they require, and form another ar- 

 rangement of the units or simply replace those which 

 have been used in their metabolism. Digestion and 

 metabolism are a sort of re-shuffling of the units. In 

 the absence of any particular unit the tissue can no 

 longer rebuild its substance, and consequently suffers. 

 The old example of the inadequacy of gelatin is now 

 explained; the tissues require tryptophan, tyrosine, 

 and cystine, and gelatin cannot provide them. 



In nutrition there are essentially two problems to 

 study : the formation of new tissue, as in the growth 

 of young animals, and the maintenance of tissue, 

 which undergoes so-called wear-and-tear, in adult 

 animals. In the latter case we have ultimately to 

 ascertain if every unit of the molecule breaks down 

 or certain selected units only. If these are in the 

 middle of a chain it would follow that the whole 

 molecule would undergo metabolism, and not units at 

 the ends alone. The problem resolves itself into 

 ascertaining the function of each amino-acid. 



Since the practical difficulties of feeding animals 

 with a mixture of pure amino-acids are far too great, 

 advantage may be taken of feeding incomplete pro- 

 teins and adding to them the missing unit or units. 



Wilcock and Hopkins made the first experiment of 

 this kind in 1906. They selected zein as protein and 

 fed it to mice, in one set alone and in another set 

 with the addition of 2 per cent, of its amount of 

 tryptophan. Young mice on zein alone immediately 

 began to lose weight and generally died in sixteen 

 days : decline in weight also occurred in the other 

 set, but with the added tryptophan death did not 

 occur until the thirtieth day. Adult mice lived twenty- 

 seven days without tryptophan, and fortv-nine days 

 with tryptophan. Tryptophan had thus an appreci- 

 able effect on the survival period of the animals. Zein 

 is incomplete in respect of other units, and death was 

 probably on this account. 



The experiment was repeated in 1916 by Ackroyd 

 and Hopkins under different, but better, conditions. 



