Vol. 68
724 _________
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COMMUNICATIONS T O T H E EDITOR METHIONINE AND ISOLEUCINE CONTENT OF MAMMALIAN HEMOGLOBINS. ITS SIGNIFICANCE FOR NUTRITIONAL AND METABOLIC STUDIES
mammals. Whereas the human, the horse and cattle need for this purpose appreciable amounts of methionine but no isoleucine, the dog on the Sirs: other hand needs isoleucine and only small Reports indicate that rats fail to grow when amounts of methionine. The amino acid comthe only dietary protein is human or beef globin position of hemoglobin is of metabolic significance unless supplemented with isoleucine.1~2~a since its breakdown contributes appreciably to Adult dogs receiving dog hemoglobin as vir- the protein economy of an animal. tually the sole source of protein maintain apThat fetal and adult bovine hernoglobins are proximate nitrogen balance with slight loss of two different proteins is again13illustrated by the eight.^,^ Dog hemoglobin supplemented with difference in their methionine and isoleucine isoleucine is no better ~ t i l i z e d .However, ~ supple- content. mentation with methionine results in positive This work was carried out in part under a nitrogen balance and maintenance of, or slight contract recommended by the Committee on gain in, weight.6 Further addition of isoleucine Medical Research, between the Office of Scientific does not iniprove the effect of m e t h i ~ n i n e . ~ ? ~ Research and Development and Columbia UniThe nutritive value of “hemoglobin” seems, versity. therefore, 1.0 depend on experimental conditions. DEPARTMENT OF BIOCHEMISTRY It will be shown, however, that the results are COLLEGEOF PHYSICIASS A N D SURGEONS exactly what could be expected from the difference COLUMBIA UNIVERSITY ERWINBRAND J E A N GRANTHAM in isoleucine and methionine content of hemo- NEW YORK, s.y. RECEIVED MARCH16, 1946 globins. From the data in the accompanying table, ISOLEUCINE AND METHIONINE CONTENT OF MAMMALIAN A NEW ALDEHYDE SYNTHESIS Sir: HEMOGLOBINS Assumed Molecular Weight = 66.700 In connection with our previous study on the ,-Isoleucine~---Methionine’ hydrogenolysis of thioacetals, it was apparent Protein,
%
0 Dog7,@ 1.36 Horse’[’ 0 10 Bovine, adultla 0 Bovine,fetal” 0.63 Humane
MIlCP g. M / m 0 0 10.4 6.9 0 0 4.80
Protein,
?’&
-
iM/lO5 g . M l m
1.32 0.42
8.85
5.9
2.81
1.76 0.97
11.8 6.50
1.9 4 L2 7.9 4.3
0
0 3.2
it can be seen that the isoleucine content of dog hemoglobin is appreciable (1.36%) whereas human, horse and adult bovine hemoglobins lack this amino acid.’4 Methionine is present in all hemoglobins studied, to the extent of 1% or higher, except in dog hemoglobin (only 0.47,). The am:ino acid requirements for hemoglobin formation would seem t o be different in different (1) :Devline and Zittle, J . B i d . Chem., 166, 393 (1944). (2) Albanese, ibid., 157, 613 (1945). (3) Orten. Bourque and Orten, i b i d . , 160, 435 (1945). (4) Whipple, Robscheit-Rohbins and Miller, A n n . N . Y . Acuiif. Sci., in press. (5) Miller, I’edevafiox Proc., 6, 73 (1946). (6) blicrobiuassay with L. arabinoius 11-5 and with L. mesenleroidec P-60, r f . Brand, el ai.,THISJ O U R N A L , 67, 1524 (1945). (7) :Microbioassay with L . mesenteroider. (8) IPreparec! by R . K. Caiman and obtained from H. B. Vickery. (9) Prepared by L. L. Miller. (10) Prepared by G. I,. Foster ( J . Bid. Chem., 169, 431 (1945)). (11) Microbioassay with L. avabinosus. (12) Brand and Kassell, Abstracts, Am. Chem. Soc., Boston meeting, Sept. 1939. (13) Prepared by Wyman, el at., J. bid. Chcm., 163, 275 (1944), and obtained from H. B. Vickery, i b i d . , 166, 283 (1944). (14) Devline a n d Zittlel and Albanese‘ report an isoleucine content of 0.29 and 0.8’7,, respectively, in human hemoglobin.
that the reductive desulfurization reaction therein described might be extended to compounds such as thiol esters in which case the corresponding aldehyde would be obtained. 0
0
/I
R-C-SR’
--t
II
R-C-H
This would be of particular interest in the sugar series since i t would constitute a new method for synthesizing aldehydo derivatives. We have established the above reaction by the hydrogenolysis of the thiol esters of benzoic, propionic and tetraacetyl-D-ribonic acids which gave benzaldehyde, propionaldehyde and aldehydo-D-ribose tetraacetate, respectively. The thiol esters were prepared by the reaction of the acid chloride with an excess of ethyl mercaptan in pyridine qr by reaction of the acid chloride with lead mercaptide in dry ether (as for ethyl thiolpropionate, b. p. 133-13.5’). The hydrogenolyses were carried out with Raney nickel in 70-8070 ethanol under reflux essentially as described‘ for the hydrogenolysis of thioacetals. After catalyst removal, benzaldehyde and propionaldehyde were isolated in the distillate as their bisulfite compounds in 60-70% yield and identified by definitive derivatives. The residual sirup obtained on hydrogenolysis of ethyl thiol(1) bI L \\c,lfrum and J V harabinos. THIS JOURNAI (1944)
66. 909
