Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1973 May;52(5):1237–1245. doi: 10.1172/JCI107291

Abnormal Fatty Acid Metabolism in Peripheral Nerves of Patients with Pernicious Anemia

Eugene P Frenkel 1,2
PMCID: PMC302380  PMID: 4700494

Abstract

Fatty acid synthesis from radiopropionate was evaluated in sural nerve biopsy slices from five normal controls and nine patients with pernicious anemia. The nerves were incubated in [14C]propionate, the lipids were extracted, and the fatty acid methyl esters were chromatographed by gas-liquid chromatography. In the normal nerves the radiolabel was found primarily in short chain (C12 and C14) fatty acids. The nerves from pernicious anemia patients showed two fatty acids peaks that were not discernible in the normal nerves, and these fatty acids had retention times intermediate to those of myristic (C14·0) and palmitic (C16·0) acids and palmitoleic (C16·1) and stearic (C18·0) acids, respectively. These two peaks (a C15 and C17 fatty acid) contained the bulk of the radioactivity recovered in the fatty acid fraction after incubation with [14C]propionate. Catalytic reduction and rechromatography failed to alter the retention time of these compounds suggesting that they are not unsaturated fatty acids. The nerves from the pernicious anemia patients had a decrease in the mean content of normal fatty acids when compared with the nerves from control patients as well as a decrease in the mean synthesis of normal fatty acids as estimated by isotope incorporation after incubation with [14C]propionate or 3H2O. Analysis of myelin isolated from the nerves indicated that the changes at least in part were in that fraction.

Full text

PDF
1237

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARDEMAN S., CHANARIN I. A METHOD FOR THE ASSAY OF HUMAN GASTRIC INTRINSIC FACTOR AND FOR THE DETECTION AND TITRATION OF ANTIBODIES AGAINST INTRINSIC FACTOR. Lancet. 1963 Dec 28;2(7322):1350–1354. doi: 10.1016/s0140-6736(63)90736-0. [DOI] [PubMed] [Google Scholar]
  2. Agrawal H. C., Banik N. L., Bone A. H., Davison A. N., Mitchell R. F., Spohn M. The identity of a myelin-like fraction isolated from developing brain. Biochem J. 1970 Dec;120(3):635–642. doi: 10.1042/bj1200635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BERRY J. F., CEVALLOS W. H., WADE R. R., Jr LIPID CLASS AND FATTY ACID COMPOSITION OF INTACT PERIPHERAL NERVE AND DURING WALLERIAN DEGENERATION. J Am Oil Chem Soc. 1965 Jun;42:492–500. doi: 10.1007/BF02540090. [DOI] [PubMed] [Google Scholar]
  4. Barley F. W., Sato G. H., Abeles R. H. An effect of vitamin B 12 deficiency in tissue culture. J Biol Chem. 1972 Jul 10;247(13):4270–4276. [PubMed] [Google Scholar]
  5. COX E. V., WHITE A. M. Methylmalonic acid excretion: an index of vitamin-B12 deficiency. Lancet. 1962 Oct 27;2(7261):853–856. doi: 10.1016/s0140-6736(62)90631-1. [DOI] [PubMed] [Google Scholar]
  6. Cardinale G. J., Dreyfus P. M., Auld P., Abeles R. H. Experimental vitamin B12 deficiency: its effect on tissue vitamin B12-coenzyme levels and on the metabolism of methylmalonyl-CoA. Arch Biochem Biophys. 1969 Apr;131(1):92–99. doi: 10.1016/0003-9861(69)90108-8. [DOI] [PubMed] [Google Scholar]
  7. Cox E. V., Robertson-Smith D., Small M., White A. M. The excretion of propionate and acetate in vitamin B12 deficiency. Clin Sci. 1968 Aug;35(1):123–134. [PubMed] [Google Scholar]
  8. Frenkel E. P., Keller S., McCall M. S. Radioisotopic assay of serum vitamin B 12 with the use of DEAE cellulose. J Lab Clin Med. 1966 Sep;68(3):510–522. [PubMed] [Google Scholar]
  9. Frenkel E. P., McCall M. S., White J. D. Recognition and resolution of errors in the radioisotopic assay of serum vitamin B12. Am J Clin Pathol. 1970 Jun;53(6):891–903. doi: 10.1093/ajcp/53.6.891. [DOI] [PubMed] [Google Scholar]
  10. Fujii K., Fukui S. Hydrocarbon-utilizing microorganism. Relationship of fatty acid composition and biosynthesis to hydrocarbon substrate and to vitamin B 12 level in Corynebacterium simplex. Eur J Biochem. 1970 Dec;17(3):552–560. doi: 10.1111/j.1432-1033.1970.tb01200.x. [DOI] [PubMed] [Google Scholar]
  11. Gompertz D., Storrs C. N., Bau D. C., Peters T. J., Hughes E. A. Localisation of enzymic defect in propionicacidaemia. Lancet. 1970 May 30;1(7657):1140–1143. doi: 10.1016/s0140-6736(70)91216-x. [DOI] [PubMed] [Google Scholar]
  12. HERBERT V., ZALUSKY R. Interrelations of vitamin B12 and folic acid metabolism: folic acid clearance studies. J Clin Invest. 1962 Jun;41:1263–1276. doi: 10.1172/JCI104589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HORNING M. G., MARTIN D. B., KARMEN A., VAGELOS P. R. Fatty acid synthesis in adipose tissue. II. Enzymatic synthesis of branched chain and odd-numbered fatty acids. J Biol Chem. 1961 Mar;236:669–672. [PubMed] [Google Scholar]
  14. HUGHES A. H., ELIASSON S. G. Synthesis of cholesterol and fatty acids in fractions of peripheral nerve. J Clin Invest. 1960 Jan;39:111–115. doi: 10.1172/JCI104009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Herbert V. Aseptic addition method for Lactobacillus casei assay of folate activity in human serum. J Clin Pathol. 1966 Jan;19(1):12–16. doi: 10.1136/jcp.19.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. JAMES A. T., LAURYSSENS M., PEETERS G. The metabolism of propionic acid. Biochem J. 1956 Dec;64(4):726–730. doi: 10.1042/bj0640726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jungas R. L. Fatty acid synthesis in adipose tissue incubated in tritiated water. Biochemistry. 1968 Oct;7(10):3708–3717. doi: 10.1021/bi00850a050. [DOI] [PubMed] [Google Scholar]
  18. KISHIMOTO Y., RADIN N. S. BIOSYNTHESIS OF NERVONIC ACID AND ITS HOMOLOGUES FROM CARBOXYL-LABELED OLEIC ACID. J Lipid Res. 1963 Oct;4:444–447. [PubMed] [Google Scholar]
  19. MAJNO G., KARNOVSKY M. L. A biochemical and morphologic study of myelination and demyelination. I. Lipide biosynthesis in vitro by normal nervous tissue. J Exp Med. 1958 Apr 1;107(4):475–496. doi: 10.1084/jem.107.4.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morrow G., 3rd, Barness L. A., Auerbach V. H., DiGeorge A. M., Ando T., Nyhan W. L. Observations on the coexistence of methylmalonic acidemia and glycinemia. J Pediatr. 1969 May;74(5):680–690. doi: 10.1016/s0022-3476(69)80130-7. [DOI] [PubMed] [Google Scholar]
  21. Morrow G., 3rd, Barness L. A. Studies in a patient with methylmalonic acidemia. J Pediatr. 1969 May;74(5):691–698. doi: 10.1016/s0022-3476(69)80131-9. [DOI] [PubMed] [Google Scholar]
  22. Mudd S. H., Levy H. L., Abeles R. H., Jennedy J. P., Jr A derangement in B 12 metabolism leading to homocystinemia, cystathioninemia and methylmalonic aciduria. Biochem Biophys Res Commun. 1969 Apr 10;35(1):121–126. doi: 10.1016/0006-291x(69)90491-4. [DOI] [PubMed] [Google Scholar]
  23. Mudd S. H., Uhlendorf B. W., Hinds K. R. Deranged B 12 metabolism: studies of fibroblasts grown in tissue culture. Biochem Med. 1970 Nov;4(3):215–239. doi: 10.1016/0006-2944(70)90050-5. [DOI] [PubMed] [Google Scholar]
  24. O'Brien J. S., Sampson E. L., Stern M. B. Lipid composition of myelin from the peripheral nervous system. Intradural spinal roots. J Neurochem. 1967 Mar;14(3):357–365. doi: 10.1111/j.1471-4159.1967.tb09532.x. [DOI] [PubMed] [Google Scholar]
  25. Reed E. B., Tarver H. Urinary methylmalonate and hepatic methylmalonyl coenzyme A mutase activity in the vitamin B12-deficient rat. J Nutr. 1970 Aug;100(8):935–947. doi: 10.1093/jn/100.8.935. [DOI] [PubMed] [Google Scholar]
  26. Rosenberg L. E., Lilljeqvist A. C., Hsia Y. E. Methylmalonic aciduria. An inborn error leading to metabolic acidosis, long-chain ketonuria and intermittent hyperglycinemia. N Engl J Med. 1968 Jun 13;278(24):1319–1322. doi: 10.1056/NEJM196806132782404. [DOI] [PubMed] [Google Scholar]
  27. Rosenberg L. E., Lilljeqvist A. C., Hsia Y. E., Rosenbloom F. M. Vitamin B12 dependent methylmalonicaciduria: defective B12 metabolism in cultured fibroblasts. Biochem Biophys Res Commun. 1969 Nov 6;37(4):607–614. doi: 10.1016/0006-291x(69)90853-5. [DOI] [PubMed] [Google Scholar]
  28. SIPERSTEIN M. D., FAGAN V. M. Studies on the relationship between glucose oxidation and intermediary metabolism. I. The influence of glycolysis on the synthesis of cholesterol and fatty acid in normal liver. J Clin Invest. 1958 Aug;37(8):1185–1195. doi: 10.1172/JCI103708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Siperstein M. D., Fagan V. M., Dietschy J. M. A gas-liquid chromatographic procedure for the measurement of mevalonic acid synthesis. J Biol Chem. 1966 Feb 10;241(3):597–601. [PubMed] [Google Scholar]
  30. Smith M. E. An in vitro system for the study of myelin synthesis. J Neurochem. 1969 Jan;16(1):83–92. doi: 10.1111/j.1471-4159.1969.tb10345.x. [DOI] [PubMed] [Google Scholar]
  31. Smith M. E., Eng L. F. The turnover of the lipid components of myelin. J Am Oil Chem Soc. 1965 Dec;42(12):1013–1018. doi: 10.1007/BF02636894. [DOI] [PubMed] [Google Scholar]
  32. Smith M. E. The turnover of myelin in the adult rat. Biochim Biophys Acta. 1968 Oct 22;164(2):285–293. doi: 10.1016/0005-2760(68)90154-9. [DOI] [PubMed] [Google Scholar]
  33. WILL J. J., MUELLER J. F., BRODINE C., KIELY C. E., FRIEDMAN B., HAWKINS V. R., DUTRA J., VILTER R. W. Folic acid and vitamin B12 in pernicious anemia; studies on patients treated with these substances over a ten year period. J Lab Clin Med. 1959 Jan;53(1):22–38. [PubMed] [Google Scholar]
  34. Ways P., Hanahan D. J. Characterization and quantification of red cell lipids in normal man. J Lipid Res. 1964 Jul;5(3):318–328. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES