The DL-hydroxy analog of methionine represents thus far the only commercial application for hydroxy or keto analogs of amino acids.
Hydroxy DL-methionine substitutes equally for methionine in chick rations (Bird, 1952; Machlin and Gordon, 1957). When a low level of soy protein was fed, methionine proved superior to methionine hydroxy analog as a supplement to promote growth (Sullivan and Bird, 1957).
When a nonspecific source of nitrogen was also supplied growth response for methionine hydroxy analog equaled that for methionine addition.
This demonstrated utilization of nonprotein nitrogen by the chick, pre-sumably for amination of the hydroxy acid.
Gordon and Sizer (1955) found DL-methionine less efficient than equimolar supplements of L-methionine, D-methionine, or methionine hydroxy analog (calcium DL-2-hydroxy, 4-methylthiobutyrate) for chick growth. Resolution of optical isomers is often an expensive and impon-derable one for the chemist. The body may expedite this job, given the proper metabolic fragments. Thus, it is conceivable that appropriate mixtures of the hydroxy or keto analogs of many or all of the essential amino acids, with adequate sources of nonspecific nitrogen sources, may in time prove advantageous for parenteral feeding.
Rose et al. (1949) made the significant disclosure that the a-keto analogs of valine and isoleucine promote excellent growth in rats as the sole sources of these amino acids. The suggestion is made that they undergo asymmetric amination in vivo to supply the corresponding L-amino acids. If the α-keto analogs are less costly to synthesize, stra-tegic use might be made of them, together with a source of ammonia, in idealized mixtures.
IX. SUMMARY
There is obvious need for general acceptance, official or otherwise, of methods to measure nutritive value of proteins. Such methods should be simple and low cost for wide application. Requirements for maximum performance should be known in terms of each amino acid, ultimately the L-amino acids. Requirements for nonspecific sources of nitrogen, to support maximum use of the essential L-amino acids, should likewise be established. The growth and repletion methods satisfy many of these criteria. Amino acid requirements, as presently established, are quite similar. Both methods clearly measure the adequacy, balance, and availability of the amino acid composition of proteins for tissue synthesis.
Careful comparisons are needed to establish their relative reliability and convenience for specific applications.
Determination of biological value has been precisely studied, but has
obvious limitations for broad applicability. It is, nevertheless, the method of choice to measure maintenance and reproduction require-ments in adults. The nitrogen balance technique can pass final judgment also as to utilization of protein hydrolyzates on injection.
These methods, properly standarized and extended to various species, appear to provide a reasonable base for broad evaluation and compari-son of amino acid mixtures, individual proteins, protein hydrolyzates, and protein foods.
The growth and repletion methods may be supplemented by calcu-dation of protein efficiency ratio, or, going further, net protein utilization.
There is considerable doubt, however, whether these refinements confer precision over the basic methods alone. In any case, final definition in terms of L-amino acids appears so close at hand as to preclude specula-tion on these points.
Space has not permitted full consideration of all of the literature and methods which deserve attention. The rat repletion method is most extensively discussed. Although highly sensitive to amino acid adequacy and balance, this method does not fully predict the value of partial protein hydrolyzates given intravenously. It serves well as a production control method, due to its rapidity and low cost.
Methods of chemical scoring provide theoretical support for bio-assay, but are now no less complicated or less costly than bio-assay. The same holds true for amino acid liberation from intact proteins by en-zymes. Thus far, direct assay of protein value by microorganisms appears to offer inadequate correlation with animal assay.
Various nonspecific forms of nitrogen support anabolism in presence of the essential amino acids. The question remains whether ammonium salt can effectively replace all or part of the nonessential amino acids.
Most studies are clearly complicated by the use of DL-amino acid mix-tures. The alpha hydroxy or keto analogs of some amino acids may avoid this complication. These basic questions will be resolved only when sufficient L-amino acids and suitable analogs are available for precise study. By the same token, amino acid requirements require re-evaluation in terms of only the L-forms.
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