THE METABOLISM OF TETRADECYLTHIOPROPIONIC ACID, A 4-THIA STEARIC-ACID, IN THE RAT - INVIVO AND INVITRO STUDIES

The metabolism of [1-C-14]tetradecylthiopropionic acid (TTP), a 4-thia stearic acid, and its sulphoxide, [1-C-14]tetradecylsulphoxypropionic acid (TTP-SO), has been studied in intact rats, in isolated rat hepatocytes, and in rat liver mitochondria. Two pathways of oxidation (beta-oxidation and omega-oxidation) have been demonstrated. TTP is incorporated, in vivo, into tissue triacylglycerol and phospholipids, it is oxidized to CO2, and it is excreted in urine, mainly as carboxypropylsulphoxypropionic acid and a little as carboxymethylsulphoxypropionic acid. TTP-SO is metabolized, in vivo, more rapidly to the same two omega-oxidation products. In hepatocytes TTP is incorporated into triacylglycerol and phospholipids even more rapidly than stearic acid. It is recovered mainly in the 1-position of phosphatidylcholine. Some is oxidized to CO2 and acid-soluble products. TTP-SO is mainly omega-oxidized to the same metabolites as are found in urine. A small fraction is incorporated into phospholipids or oxidized to CO2. In isolated mitochondria [1-C-14]TTP is converted into (CO2)-C-14, radioactive malonic semialdehyde, and addition products of malonic semialdehyde. In the presence of phenylhydrazine. malonic semialdehyde phenylhydrazone is the dominating product. In soluble extracts of mitochondria [1-C-14]malonic semialdehyde is oxidized directly to (CO2)-C-14 in the presence of CoA and NAD+, probably by the (methyl)malonic acid semialdehyde dehydrogenase (EC 1.2.1.27).