METABOLIC IMPORTANCE OF AMINO ACID—-LIPID COMPLEXES 757 
amino acid—lipid complexes, some features of these studies should be mentioned. 
First, it was found in collaboration with Dr. R. B. RoBerts and K. McQuiL_Lan 
at the Carnegie Institution of Washington, that amino acid—lipid complexes do form. 
Amino acid in these complexes was in a dynamic state as opposed to a stable end 
product type of labeling. When in subsequent experiments with Dr. R. B. RoBERtTs, 
Dr. R. BRITTEN and Dr. F. DuGGAN, we took special pains to obtain a clean ribosome 
preparation from £. colt we found that more radioactive amino acid—lipid complex 
was obtained from the ribosome preparation than from the cell wall fraction. Other 
experiments showed that the amino acid lipid complexes appear to form at the cell 
wall site before the internal pool became labeled. We currently are studying mutants 
of E. coli obtained from Dr. M. Lusrn of the Harvard University. These mutants can no 
longer concentrate proline and we are trying to see if this defect is in any way related 
to the manner in which these mutants handle proline—lipid complexes. 
At the present time, I think we can safely say that associations between amino 
acids and peptides with lipids do occur in a wide variety of living tissues and that 
they are not artefacts of preparation. In those cases where the metabolic state of the 
amino acid has been examined using radioactive tracers, it has been found that the 
amino acid association is dynamic and not static. Many of the properties of these 
complexes, as already described in this paper, indicate that they are undergoing 
active metabolism. Briefly restated, these are: generality with respect to different 
tissues and amino acids; sensitivity of formation of certain complexes to chloram- 
phenicol, dinitrophenol and conditions which inhibit protein synthesis; sensitivity of 
protein synthesis to conditions with interfere with lipids; structural specificity regard- 
ing the amino acid; demonstration of the participation of chemical bonds requiring 
active metabolism such as peptide bonds, ester bonds and acylamides and the rapid 
labeling of these complexes with amino acid as compared to the kinetics for nucleic 
acids and proteins. 
The idea that non-polar forms of amino acid may be of metabolic importance is 
not unrealistic. The first stage in the metabolism of amino acid, that is, getting it 
into the cell, is a problem of bringing the amino acid through a barrier of a non-polar 
medium. One way of doing this would be to confer upon the amino acid, lipid solubility 
for its passage through the cell membrane. This possibility is currently being actively 
pursued in the laboratories of GABy and TRIA as well as ROBERTS, BRITTEN and our 
own. The other major possibility for the metabolic significance of these complexes 
is the process of protein synthesis*. Considerations which tend to support this picture 
are as follows*: the microsomal system has been revealed as the structural element 
most directly concerned with large-scale protein synthesis in the cytoplasm; in 
systems where protein synthesis and secretion are particularly active processes, the 
microsomal system consists of a lipid membrane containing in it, or on it, ribonu- 
cleoprotein-rich areas. In other active systems lacking a demonstrable endoplasmic 
reticulum, other lipid surfaces such as the cellular membrane may be similarly in- 
volved or the ribosome themselves may possess a membrane-like component (in this 
connection, there is a lipid-rich high-specific activity component isolated from 
labeled pea seedling ribosomes by T’so). Recent electron-microscope studies and 
refined fractional centrifugation indicate an intimate association of lipid and nucleo- 
* References for statements in the following discussion can be found in ref. 4. 
References p. 758 
