Isolation and characterization of a Chinese hamster ovary cell line deficient in fatty alcohol:NAD+ oxidoreductase activity.
We have isolated a mutant Chinese hamster ovary cell line that is defective in long-chain fatty alcohol oxidation. The ability of the mutant cells to convert labeled hexadecanol to the corresponding fatty acid in vivo was reduced to 5% of the parent strain. Whole-cell homogenates from the mutant strain, FAA.1, were deficient in long-chain fatty alcohol:NAD+ oxidoreductase (FAO; EC 1.1.1.192) activity, which catalyzes the oxidation of hexadecanol to hexadecanoic acid, although the intermediate fatty aldehyde was formed normally. A direct measurement of fatty aldehyde dehydrogenase showed that the FAA.1 strain was defective in this component of FAO activity. FAA.1 is a two-stage mutant that was selected from a previously described parent strain, ZR-82, which is defective in ether lipid biosynthesis and peroxisome assembly. Because of combined defects in ether lipid biosynthesis and fatty alcohol oxidation, the ability of the FAA.1 cells to incorporate hexadecanol into complex lipids was greatly impaired, resulting in a 60-fold increase in cellular fatty alcohol levels. As the FAO deficiency in FAA.1 cells appears to be identical to the defect associated with the human genetic disorder Sjögren-Larsson syndrome, the FAA.1 cell line may be useful in studying this disease.
Department of Biophysics, Boston University School of Medicine, MA 02118.
P F
PF
James
W B
WB
Rizzo
J
J
Lee
R A
RA
Zoeller
D000429:Alcohol Oxidoreductases / Q000172:deficiency / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005233:Fatty Alcohols / Q000378:metabolism; D005260:Female; D007700:Kinetics; D009154:Mutation; D010053:Ovary; D010084:Oxidation-Reduction; D010169:Palmitic Acids / Q000378:metabolism
D000447:Aldehydes; D005233:Fatty Alcohols; D010169:Palmitic Acids; D000429:Alcohol Oxidoreductases; C065402:long-chain-alcohol dehydrogenase; D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase; C001647:hexadecanal