758 R. W. HENDLER 
protein. Studies with secretory tissues suggest that newly synthesized proteins are 
associated with lipid. In a wide variety of tissues, amino acid has been observed to 
enter quickly into a lipid-soluble form. We thus have a situation in which the ma- 
chinery for protein synthesis as well as its initial reactants and final products have 
been found in lipid soluble forms. The working hypothesis that amino acid derivatives 
may be condensed in the lipid medium to form protein, seems at the present time to 
be extremely practical. Indeed, the possibility should be seriously considered that 
transport and synthesis may be linked metabolic events. 
One other aspect of the problem seems worthy of mention. That is the method of 
energizing peptide bond formation. Contrary to popular belief, this question at the 
time of writing is not settled. The wealth of literature concerning amino acid activa- 
tion and S-RNA becomes very sparse as we approach biological systems making 
discrete proteins. The passage of electrons through components of lipid membranes 
during which process energy is released and stored is currently being elucidated. In 
the most familiar energy-requiring process, this energy is stored in water-soluble 
“high-energy compounds” which circulate in the aqueous part of the cell where they 
are utilized. 
If there are complex processes in a lipid phase which require energy, it seems 
possible that energy could be directly utilized in the lipid phase without the partici- 
pation of the common aqueous “high-energy” carriers. If this is so, one must be very 
careful in studying the energy requirements of such a system on the basis of tech- 
niques which in the past have been used in connection with energy-requiring steps 
in the aqueous phase. 
The considerations developed here have been presented in general terms. At the 
present state of our knowledge or more accurately, lack of knowledge, more detailed 
speculations and presentation of models is premature. We must realize that at the 
present time, the metabolic importance of amino acid—lipid complexes, AMP-amino 
acids, and S-RNA-amino acids has not been firmly established and therefore the 
further investigation of these materials must be pursued in various laboratories. 
REFERENCES 
1 J. WESTLEY, J. J. WREN AND H. K. MitcHeELt, J. Biol. Chem., 229 (1957) 131. 
2, R. W. HENDLER, Science, 128 (1958) 143. 
3. R. W. HENDLER, J. Biol. Chem., 234 (1959) 1466. 
4 R. W. HENDLER, Biochim. Biophys. Acta, 49 (1961) 297. 
° J. L. Harnina, T. Fuxur anp B. AXELROD, J. Am. Chem. Soc., 81 (1959) 1259. 
6 J. L. Harnine, T. Fukui anp B. AxELRopD, J. Biol. Chem., 235 (1960) 760. 
* T. Fukui AND B. AXELROD, J. Biol. Chem., 236 (1961) 811. 
8 E. A. PETERSON AND D. M. GREENBERG, J. Biol. Chem., 194 (1952) 359. 
° G. D. HUNTER anD R. A. GoopsaLL, Biochem. J., 78 (1961) 564. 
10 W.L. GasBy, R. N. NAUGHTEN AND C. LoGaN, Arch. Biochem. Biophys., 82 (1959) 34. 
‘l 'W. L. GaBy AND R. SILBERMAN, Arch. Biochem. Biophys., 87 (1960) 188. 
122 W.L. Gasy, H. L. Worin anp I. Zajac, Cancer Research, 20 (1960) 1508. 
138 J. J. WREN AND H. K. MitcHELt, Proc. Soc. Exptl. Biol. Med., 99 (1958) 431. 
M4 J. J. Wren anv H. K. MitcueE tt, J. Biol. Chem., 234 (1959) 2823. 
16 J. J. WREN, Nature, 185 (1960) 295. 
16 QO. BARNABEI AND R. FERRARI, Arch. Biochem. Biophys., 94 (1961) 79. 
