On Specific Dynamic Action, Turnover, and Protein Synthesis

ON SPECIFIC DYNAMIC ACTION, TURNOVER, AND PROTEIN SYNTHESIS SANTIAGO GRISOLIA AND JAMES KENNEDY* It is well established that the increased heat production by animals following the ingestion of food, particularly protein, called "specific dynamic action" (SDA) is related to metabolism. While numerous proposals have been advanced to explain the phenomenon, none is entirely satisfactory. H. A. Krebs [?, 2] offered a new approach to the problem by relating the quantity ofATP synthesis1 to the caloric values for the type offoodstuffwhich supplies the energy for ATP synthesis. The additional calories that he calculated to be necessary for formation of a given amount of ATP when protein serves as the fuel as compared to carbohydrate (see below) were said to represent the SDA ofprotein. In other words, on a caloric basis, more protein than carbohydrate must be ingested to obtain the same quantity ofATP, and this caloric difference constitutes the SDA. Since the most recent values calculated on this basis by Krebs [1] agreed well with those obtained by direct measurement, he considered the SDA a solved issue. The purpose of the present discussion is to point out that, insofar as SDA is concerned, these calculations may be misleading; however, they typify once more the pioneering spirit of Sir Hans, for without doubt this type of correlation between molecular events and whole animal parameters is most timely. While realizing their limitations, such calculations are of interest for they provide approximate limits within which * Department of Biochemistry, University of Kansas Medical Center, Kansas City. This work was supported in part by U.S. Public Health Service grants AM-01855 and AI-03505 and by the Kansas Heart and Cancer Association. 1 In this paper, for simplification and for consistency with Krebs's nomenclature, ATP synthesis refers to the esterification ofphosphate forming the terminal bond ofATP. 578 Santiago Grisolia andJames Kennedy · Protein Synthesis Perspectives in Biology and Medicine · Summer 1966 postulations regarding metabolic pathways must remain. The accuracy of such calculations and their future modifications will increase as our knowledge ofintermediary metabolism, particularly regulation, advances. Krebs calculated the SDA ofprotein in the following manner: Assuming complete oxidation, 38 moles ofATP should be obtained from 1 mole of glucose residue (molecular weight = 162) in starch. The caloric yield of carbohydrate in the body is 4.1 kcal/gram. Therefore, (4.1 X i62)/38 = 17.4. It follows, then, that 17.4 kcal, are required to obtain 1 mole of ATP when carbohydrate serves as the fuel [2]. Krebs [1] estimated the gross maximum amount of ATP that could be obtained from a mole of each of the various amino acids present in proteins on the basis of their oxidation and on the assumption that all oxidative steps are effectively coupled with phosphorylation. Using two additional assumptions, he subtracted from this gross ATP yield: (a) 2 moles ofATP for disposal of each gram atom of amino acid nitrogen via urea synthesis; (b) 12 per cent, which represents the amount of amino acid carbon which is not oxidized and therefore leaves the body without contributing to ATP formation. From the resulting net ATP yield per mole of each amino acid and the reported amino acid composition for ovalbumin [3], Krebs calculated the net ATP yield per 100 gm. of this protein to be 20.1 moles. Assuming that the heat yield of protein is 4.25 kcal/gram [2, 4], (4.25 X ioo)/20.i = 21.2; therefore, 21.2 kcal, would be required to obtain 1 mole of ATP when protein is utilized. The SDA was then calculated . As shown in Part I ofTable 1 for ovalbumin, it would be (21.2 — i74)/i7.4 X ioo = 21.8 per cent. As indicated above, Krebs considered the ATP required for urea formation and the incomplete oxidation of amino acid carbon as avenues of ATP loss. He did not deduct for the utilization of ATP in glutamine synthesis, both for other biosynthetic pathways (e.g., purines and amino sugars) and for storage or transport of ammonia; the latter may be of consequence particularly after ingestion ofa large protein meal, in which case the urea cycle may be working at capacity and be inefficient, that is, consuming...