Rates of Reactions Involved in Phosphatide Synthesis in Liver and Small Intestine of Intact Rats

The incorporation of administered bases into phosphatides and the conversion of serine to ethanolamine and choline in mammalian tissues have been known since the studies of Stetten with the use of ‘SN-labeled compounds (2, 3). The detailed enzymatic steps for these reactions, demonstrated largely by Kennedy and associates, have been recently reviewed (4). These workers showed that phosphatidylcholine and phosphatidylethanolamine are synthesized from phosphocholine and phosphoethanolamine by way of the cytidine diphosphate derivatives. Serine is incorporated into phosphatides by the exchange of free serine with the ethanolamine of phosphatidylethanolamine. The decarboxylation of serine to ethanolamine has been demonstrated to occur only via the phosphatidyl derivatives. Likewise, the methylation of ethanolamine apparently takes place only in the lipid form (5, 6). The rates of turnover of phosphatides have been studied with the use of 3*P-labeled phosphate (7-10) and, more recently, with 1Glabeled serine (II). Conclusions from these studies have been limited by a lack of knowledge of the individual enzymatic steps in phosphatide synthesis. In this study the rates of these individual steps have been evaluated in small intestine and liver of the intact rat. Serine3-r% has been administered to rats, and the specific activities of the precursor and product of each reaction have been determined as a function of time. By the use of appropriate models, individual rates have been calculated for each of the reactions known to be involved in phosphatide synthesis. The results give rates considerably faster than those indicated by earlier studies of phosphatide turnover. The present studies show also that rates of synthesis via the cytidine diphosphate pathway are an order of magnitude greater than t,he rates of other reactions involved in phosphatide synthesis. A scheme of the reactions studied is shown in Fig. 1.