Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1970 Mar;117(1):177–181. doi: 10.1042/bj1170177

Gluconeogenesis from propionate in kidney and liver of the vitamin B12-deficient rat

M J Weidemann 1,*, R Hems 1, D L Williams 1, G H Spray 1, H A Krebs 1
PMCID: PMC1178844  PMID: 5420952

Abstract

1. Kidney-cortex slices and the perfused livers of vitamin B12-deficient rats removed propionate from the incubation and perfusion media at 33 and 17% respectively of the rates found with tissues from rats receiving either a normal or a vitamin B12-supplemented diet. There was a corresponding fall in the rates of glucose synthesis from propionate in both tissues. 2. The addition of hydroxocobalamin or dimethylbenzimidazolylcobamide coenzyme to kidney-cortex slices from vitamin B12-deficient rats in vitro failed to restore the normal capacity for propionate metabolism. 3. Although the vitamin B12-deficient rat excretes measurable amounts of methylmalonate, no methylmalonate production could be detected (probably because of the low sensitivity of the method) when kidney-cortex slices or livers from deficient rats were incubated or perfused with propionate. 4. The addition of methylmalonate (5mm) to kidney-cortex slices from rats fed on a normal diet inhibited gluconeogenesis from propionate by 25%. 5. Methylmalonate formation is normally only a small fraction of the flux through methylmalonyl-CoA. This fraction increases in vitamin B12-deficient tissues (as shown by the urinary excretion of methylmalonate) presumably because the concentration of methylmalonyl-CoA rises as a result of low activity of methylmalonyl-CoA mutase (EC 5.4.99.2). Slow removal of methylmalonyl-CoA might depress propionate uptake owing to the reversibility of the steps leading to methylmalonyl-CoA formation.

Full text

PDF
180

Selected References

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

  1. Baird G. D., Hibbitt K. G., Hunter G. D. Biochemical aspects of bovine ketosis. Biochem J. 1968 May;107(5):683–689. doi: 10.1042/bj1070683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Gevers W., Krebs H. A. The effects of adenine nucleotides on carbohydrate metabolism in pigeon-liver homogenates. Biochem J. 1966 Mar;98(3):720–735. doi: 10.1042/bj0980720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Giorgio A. J., Plaut G. W. A method for the colorimetric determination of urinary methylmalonic acid in pernicious anemia. J Lab Clin Med. 1965 Oct;66(4):667–676. [PubMed] [Google Scholar]
  6. Hems R., Ross B. D., Berry M. N., Krebs H. A. Gluconeogenesis in the perfused rat liver. Biochem J. 1966 Nov;101(2):284–292. doi: 10.1042/bj1010284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. JUNGALWALA F. B., CAMA H. R. PREPARATION AND PROPERTIES OF 5,6-MONOEPOXYVITAMIN A ACETATE, 5,6-MONOEPOXYVITAMIN A ALCOHOL, 5,6-MONOEPOXYVITAMIN A ALDEHYDE AND THEIR CORRESPONDING 5,8-MONOEPOXY (FURANOID) COMPOUNDS. Biochem J. 1965 Apr;95:17–26. doi: 10.1042/bj0950017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KULKA R. G., KREBS H. A., EGGLESTON L. V. The reduction of acetoacetate to beta-hydroxybutyrate in animal tissues. Biochem J. 1961 Jan;78:95–106. doi: 10.1042/bj0780095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Krebs H. A., De Gasquet P. Inhibition of gluconeogenesis by alpha-oxo acids. Biochem J. 1964 Jan;90(1):149–154. doi: 10.1042/bj0900149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lengyel P., Mazumder R., Ochoa S. MAMMALIAN METHYLMALONYL ISOMERASE AND VITAMIN B(12) COENZYMES. Proc Natl Acad Sci U S A. 1960 Oct;46(10):1312–1318. doi: 10.1073/pnas.46.10.1312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MARSTON H. R., ALLEN S. H., SMITH R. M. Primary metabolic defect supervening on vitamin B12 deficiency in the sheep. Nature. 1961 Jun 17;190:1085–1091. doi: 10.1038/1901085a0. [DOI] [PubMed] [Google Scholar]
  12. SERLIN I., COTZIAS G. C. Microdiffusion of acetic acid as an assay for acetylcholinesterase. J Biol Chem. 1955 Jul;215(1):263–268. [PubMed] [Google Scholar]
  13. Weidemann M. J., Krebs H. A. Acceleration of gluconeogenesis from propionate by Dl-carnitine in the rat kidney cortex. Biochem J. 1969 Jan;111(1):69–81. doi: 10.1042/bj1110069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Weissbach H., Toohey J., Barker H. A. ISOLATION AND PROPERTIES OF B(12) COENZYMES CONTAINING BENZIMIDAZOLE OR DIMETHYLBENZIMIDAZOLE. Proc Natl Acad Sci U S A. 1959 Apr;45(4):521–525. doi: 10.1073/pnas.45.4.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Williams D. L., Spray G. H., Newman G. E., O'Brien J. R. Dietary depletion of vitamin B12 and the excretion of methylmalonic acid in the rat. Br J Nutr. 1969 Jun;23(2):343–352. doi: 10.1079/bjn19690041. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES