Myocardial metabolism of radioiodinated methyl-branched fatty acids.

Methylated fatty acids labeled with radioactive iodine have been proposed as a means of studying regional myocardial uptake of fatty acids in man. To investigate the methylated fatty acid that is best adapted for an assessment of uptake, we have studied the influence of the number and the position of the methyl groups of IFA intracellular metabolism; 16-iodo-2-methyl-hexadecanoic (mono-alpha), 16-iodo-2,2-methyl hexadecanoic (di-alpha), 16-iodo-3-methyl-hexadecanoic (mono-beta), and 16-iodo-3,3-methyl-hexadecanoic (di-beta) acids were injected into the coronary arteries of isolated rat hearts. Intracellular analysis shows that the degradation of mono-alpha was always lower than that of IHA and the storage was always much higher. The differences between mono-beta and IHA were similar to those observed with mono-alpha, but were much more pronounced. With the two dimethylated IFAs there was an inhibition of both oxidation and esterification which led to an accumulation of free FAs in myocardial cells. In conclusion, mono-beta, di-alpha, and di-beta are potentially suitable for studying the cellular uptake of IFA since all of them, and particularly the dimethylated IFAs, have a low oxidation rate.

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes.

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be beta oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be beta oxidized only after an initial alpha oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me2) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me2) which cannot be beta oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-14C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid greater than 16-iodo-3-R,S-methyl palmitic acid greater than 16-iodo-2-R,S-methyl palmitic acid greater than 16-iodo-2,2-dimethyl palmitic acid greater than 16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethyl-branched iodo fatty acids as compared to the monomethyl ones and palmitic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis of 15-(p-iodophenyl) pentadecanoic acid labelled with carbon-14.

15-(p-Iodophenyl) pentadecanoic acid labelled with carbon-14 in the carboxyl group is obtained with good yields in five steps from [14C]NaCN, starting from 14-bromo 1-phenyl tetradecane 2. Specific radioactivity: 0.019 mCi/mg, 8.45 mCi/mmol; radiochemical yield: 74.6%.

Kinetics of iodomethylated hexadecanoic acid metabolism in the rat myocardium: influence of the number and the position of methyl radicals.

The methyl-branched fatty acids, if radioiodine labelled in alpha position, are potentially adapted to a selective study of FA myocardial uptake. To determine the position and the number of methyl radicals that are necessary to obtain a maximal uptake and a minimal degradation, we measured time-activity evolution of isolated and perfused rat hearts after an injection of iodinated fatty acids which are mono- or dimethylated in alpha or beta position. Except for dimethyl fatty acid, the uptake is similar for all fatty acids studied to that of the straight chain analogue; beta mono- or dimethyl fatty acids seem best adapted to a study of the uptake because alpha monomethyl fatty acids undergo a metabolic degradation and alpha mono- and dimethyl fatty acids induce ventricular fibrillations.

Iodomethylated fatty acid metabolism in mice and dogs.

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono beta) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono beta into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.