The effects of alkylthioacetic acids (3-thia fatty acids) on fatty acid metabolism in isolated hepatocytes.
Long-chain alkylthioacetic acids (3-thia fatty acids) inhibit fatty acid synthesis from [1-14C]acetate in isolated hepatocytes, while fatty acid oxidation is nearly unaffected or even stimulated. Desaturation of [1-14C]stearate (delta 9-desaturase) is also unaffected. [1-14C]Dodecylthioacetic acid (a 3-thia fatty acid) is incorporated in triacylglycerol and in phospholipids more efficiently than [1-14C]palmitate in isolated hepatocytes. The metabolism of [1-14C]dodecylthioacetic acid to acid-soluble products (by omega-oxidation) is slow compared to the oxidation of [1-14C]palmitate. In hepatocytes from adapted rats (rats fed tetradecylthioacetic acid for 4 days) the rate of [1-14C]palmitate oxidation is increased and its rate of esterification is decreased. Stearate desaturation is also decreased. The rate of cyanide-insensitive peroxisomal fatty acid beta-oxidation is several-fold increased. The metabolic effects of long-chain 3-thia fatty acids are discussed and it is concluded that they behave essentially like normal fatty acids except for their slow breakdown due to the sulfur atom in the 3 position, which blocks normal beta-oxidation.
Skrede
S
S
Institute of Medical Biochemistry, University of Oslo, Norway.
Narce
M
M
Bergseth
S
S
Bremer
J
J
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004435:Eating; D004952:Esters; D005215:Fasting; D005227:Fatty Acids / Q000138:chemical synthesis / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D007461:Iodoacetates / Q000378:metabolism; D019807:Iodoacetic Acid; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013229:Stearic Acids / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000378:metabolism
D000085:Acetates; D004952:Esters; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007461:Iodoacetates; D010169:Palmitic Acids; D013229:Stearic Acids; D013438:Sulfhydryl Compounds; D019308:Palmitic Acid; C031183:stearic acid; D019807:Iodoacetic Acid