Journal of Inherited Metabolic Disease

, Volume 12, Issue 1, pp 47–57 | Cite as

Abnormal fatty acid composition of biotin-responsive multiple carboxylase deficiency fibroblasts

  • S. Packman
  • S. C. Whitney
  • M. Fitch
  • S. E. Fleming


Clinical and biochemical correlations in the biotin-responsive multiple carboxylase deficiencies have suggested that disordered lipogenesis plays a role in the pathogenesis of the disease. In particular, the activity of biotin-dependent acetyl CoA carboxylase and thede novo synthesis of fatty acids are reduced in mutant fibroblasts. In the present work, we examine the biochemical consequences of these deficiencies, and document and characterize an abnormal fatty acid composition in holocarboxylase synthetase deficiency fibroblasts. Following growth in biotin-restricted medium, the total fatty acid content of mutant cells is reduced. There were significant reductions in the percentage as 16:0, 18:0 and 20:3N9 fatty acids, with the proportion of longer-chain fatty acids either increased or maintained at control levels. The cellular content of 16:0, 16:1, 18:0, 18:1 and 20:3N9 fatty acids was reduced, while that of the longer-chain fatty acids was preserved at control levels in mutant cells deprived of biotin. We speculate that the components of the altered fatty acid pools may be disproportionately incorporated into complex lipids in mutant cells, with pathologic effects on the multiple carboxylase deficiency phenotype.


Total Fatty Acid Fatty Acid Content Mutant Cell Total Fatty Acid Content Altered Fatty Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bartlett, K. and Gompertz, D. Biotin activation of carboxylase activity in cultured fibroblasts.Clin. Chim. Acta 84 (1978) 399–401PubMedGoogle Scholar
  2. Blom, W., de Muinck Keizer, S. and Scholte, H. Acetyl CoA carboxylase deficiency: an inborn error ofde novo fatty acid synthesis.N. Engl. J. Med. 305 (1981) 465–466PubMedGoogle Scholar
  3. Burri, B., Sweetman, L. and Nyhan, W. Mutant holocarboxylase synthetase: evidence for the enzyme defect in early infantile biotin-responsive multiple carboxylase deficiency.J. Clin. Invest. 68 (1981) 1491–1495PubMedGoogle Scholar
  4. Cowan, M., Wara, D., Packman, S., Ammann, A., Yoshino, M., Sweetman, L. and Nyhan, W. Multiple biotin dependent carboxylase deficiencies associated with defects in T and B cell immunity.Lancet 2 (1979) 115–118PubMedGoogle Scholar
  5. Crocker, P., Fitch, M. and Ostwald, R. Effects of the unsaturation of dietary fat and of arachidonate supplementation on cholesterol pool expansion in the guinea pig.J. Nutr. 109 (1979) 927–938PubMedGoogle Scholar
  6. Dixon, W. and Massey, F. Jr.Introduction to Statistical Analysis. McGraw-Hill, New York, 1969Google Scholar
  7. Donaldson, W. Biotin effects on fatty acids synthesis in chicks.Ann. NY Acad. Sci. 447 (1985) 104–111Google Scholar
  8. Feldman, G. and Wolf, B. Deficient acetyl CoA carboxylase activity in multiple carboxylase deficiency.Clin. Chim. Acta 111 (1981) 147–151PubMedGoogle Scholar
  9. Fretag, S. and Utter, M. Introduction of pyruvate carboxylase in 3T3-L1 cells.Proc. Natl. Acad. Sci. USA 77 (1980) 1321–1325PubMedGoogle Scholar
  10. Ginsburg, R., Robertson, A. and Michel, B. Acrodermatitis enteropathica: abnormalities of fat metabolism.Arch. Dermatol. 112 (1976) 653–660PubMedGoogle Scholar
  11. Gonzalez-Rios, M. C., Whitney, S., Williams, M., Elias, P. and Packman, S. Lipid metabolism in biotin-responsive multiple carboxylase deficiency.J. Inher. Metab. Dis. 8 (1985) 184–186PubMedGoogle Scholar
  12. Kim, K. H. Control of acetyl-CoA carboxylase by covalent modification.Mol. Cell Biochem. 28 (1979) 28–43Google Scholar
  13. Markwell, M., Haas, S., Bieber, L. and Tolbert, N. A modification of the Lowry procedure to simplify protein determination in membrane acid lipoprotein samples.Anal. Biochem. 87 (1978) 206–210PubMedGoogle Scholar
  14. Mock, D., deLorimer, A., Liebman, W., Sweetman, L. and Baker, H. Biotin deficiency: an unusual complication of parenteral alimentation.N. Engl. J. Med. 304 (1981) 820–823PubMedGoogle Scholar
  15. Munnich, A., Saudubray, J., Coude, F., Charpentier, C., Saurat, J. and Frezal, J. Fattyacid responsive alopecia in multiple carboxylase deficiency.Lancet 1 (1980) 1080–1081Google Scholar
  16. Ostwald, R., Yamanaka, W. and Light, M. The phospholipids of liver, plasma and red cells in guinea pigs.Proc. Soc. Exp. Biol. Med. 1345 (1970) 814–820Google Scholar
  17. Packman, S., Caswell, N. and Baker, H. Biochemical evidence for diverse etiologies in biotin-responsive multiple carboxylase deficiency.Biochem. Genet. 20 (1982a) 17–28PubMedGoogle Scholar
  18. Packman, S., Caswell, N., Gonzalez-Rios, M. C., Kadlecek, T., Cann, H., Rassin, D. and McKay, C. Acetyl CoA carboxylase in cultured fibroblasts: differential biotin dependence in the two types of biotin-responsive multiple carboxylase deficiency.Am. J. Hum. Genet. 36 (1984) 80–92PubMedGoogle Scholar
  19. Packman, S., Cowan, M., Golbus, M., Caswell, N., Sweetman, S., Burri, B., Nyhan, W. and Baker, H. Prenatal treatment of biotin-responsive multiple carboxylase deficiency.Lancet 1 (1982b) 1435–1439PubMedGoogle Scholar
  20. Packman, S., Sweetman, L., Baker, H. and Wall, S. The neonatal form of biotin-responsive multiple carboxylase deficiency.J. Pediatr. 99 (1981) 418–420PubMedGoogle Scholar
  21. Proud, V., Patterson, J., Rizzo, W. and Wolf, B. Skin abnormalities in biotinidase deficiency may be associated with alterations in fatty acid composition.Am. J. Hum. Genet. 39 (1986) A18Google Scholar
  22. Sander, J., Malamud, N., Cowan, M., Packman, S., Ammann, A. and Wara, D. Intermittent ataxia, organic aciduria and immunodeficiency: a vitamin responsive disorder.Ann. Neurol. 8 (1980) 544–547PubMedGoogle Scholar
  23. Saunders, M., Sherwood, W., Duthie, M., Surh, L. and Gravel, R. Evidence for a defect of holocarboxylase synthetase activity in cultured lymphoblasts from a patient with biotinresponsive multiple carboxylase deficiency.Am. J. Hum. Genet. 34 (1982) 590–601PubMedGoogle Scholar
  24. Shafrir, E. and Bierman, E. Acetyl-CoA carboxylase activity in cultured human fibroblasts: induction by insulin in relation to cell growth and triacylglycerol metabolism.Biochim. Biophys. Acta 663 (1981) 432–445PubMedGoogle Scholar
  25. Sweetman, L., Bates, S., Hull, D. and Nyhan, W. Propionyl CoA carboxylase deficiency in a patient with biotin-responsive 3-methylcrotonyl glycinuria.Pediatr. Res. 11 (1977) 1144–1147PubMedGoogle Scholar
  26. Sweetman, L. and Nyhan, W. Inheritable biotin-treatable disorders and associated phenomena.Annu. Rev. Nutr. 6 (1986) 317–343PubMedGoogle Scholar
  27. Thompson, G.The Regulation of Membrane Lipid Metabolism. CRC Press, Boca Raton, 1980Google Scholar
  28. Williams, M., Packman, S. and Cowan, M. Alopecia and periorificial dermatitis in biotinresponsive multiple carboxylase deficiency.J. Am. Acad. Dermatol. 9 (1983) 97–103PubMedGoogle Scholar
  29. Wolf, B., Grier, R., Allen, R., Goodman, S. and Kien, C. Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency.Clin. Chim. Acta 131 (1983) 273–281PubMedGoogle Scholar

Copyright information

© SSIEM and Kluwer Academic Publishers 1989

Authors and Affiliations

  • S. Packman
    • 1
  • S. C. Whitney
    • 1
  • M. Fitch
    • 2
  • S. E. Fleming
    • 2
  1. 1.Division of Genetics, Department of PediatricsUniversity of CaliforniaSan Francisco
  2. 2.Department of Nutritional SciencesUniversity of CaliforniaBerkeleyUSA

Personalised recommendations