Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1972 Jul;128(3):677–684. doi: 10.1042/bj1280677

The effect of phenylpyruvate on pyruvate metabolism in rat brain

Mulchand S Patel 1
PMCID: PMC1173818  PMID: 4634834

Abstract

1. The effect of phenylalanine and phenylpyruvate on the metabolism of pyruvate by isolated mitochondria from rat brain was investigated. 2. Phenylpyruvate inhibited the fixation of H14CO3− in the presence of pyruvate by intact rat brain mitochondria, whereas phenylalanine and other metabolites of this amino acid had no inhibitory effect on this process. 3. Pyruvate carboxylase activity in freeze-dried rat brain mitochondrial preparations was also inhibited only by phenylpyruvate, and a `mixed type' inhibition was observed. 4. The Km for pyruvate of rat brain pyruvate carboxylase was about 0.2mm. 5. The concentration of phenylpyruvate required for a 50% inhibition of H14CO3− fixation by the intact mitochondria and of pyruvate carboxylase activity was dependent on the concentration of pyruvate used in the incubation medium. 6. The possible significance of inhibition of pyruvate carboxylase activity by phenylpyruvate in the brains of phenylketonuric patients is discussed.

Full text

PDF
677

Selected References

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

  1. Agrawal H. C., Bone A. H., Davison A. N. Effect of phenylalanine on protein synthesis in the developing rat brain. Biochem J. 1970 Apr;117(2):325–331. doi: 10.1042/bj1170325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ballard F. J., Hanson R. W. The citrate cleavage pathway and lipogenesis in rat adipose tissue: replenishment of oxaloacetate. J Lipid Res. 1967 Mar;8(2):73–79. [PubMed] [Google Scholar]
  3. Barbato L., Barbato I. W., Hamanaka A. The in vivo effect of high levels of phenylalanine on lipids and RNA of the developing rabbit brain. Brain Res. 1968 Mar;7(3):399–406. doi: 10.1016/0006-8993(68)90006-1. [DOI] [PubMed] [Google Scholar]
  4. Benuck M., Stern F., Lajtha A. Transamination of amino acids in homogenates of rat brzain. J Neurochem. 1971 Aug;18(8):1555–1567. doi: 10.1111/j.1471-4159.1971.tb00017.x. [DOI] [PubMed] [Google Scholar]
  5. CARVER M. J. INFLUENCE OF PHENYLALANINE ADMINISTRATION ON THE FREE AMINO ACIDS OF BRAIN AND LIVER IN THE RAT. J Neurochem. 1965 Jan;12:45–50. doi: 10.1111/j.1471-4159.1965.tb10250.x. [DOI] [PubMed] [Google Scholar]
  6. CROME L., TYMMS V., WOOLF L. I. A chemical investigation of the defects of myelination in phenylketonuria. J Neurol Neurosurg Psychiatry. 1962 May;25:143–148. doi: 10.1136/jnnp.25.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carver M. J., Copenhaver J. H., Serpan R. A. Free amino acids in foetal rat brain. Influence of l-phenylalanine. J Neurochem. 1965 Sep-Oct;12(9):857–861. doi: 10.1111/j.1471-4159.1965.tb10271.x. [DOI] [PubMed] [Google Scholar]
  8. Chase H. P., O'Brien D. Effect of excess phenylalanine and of other amino acids on brain development in the infant rat. Pediatr Res. 1970 Jan;4(1):96–102. doi: 10.1203/00006450-197001000-00012. [DOI] [PubMed] [Google Scholar]
  9. Clark J. B., Nicklas W. J. The metabolism of rat brain mitochondria. Preparation and characterization. J Biol Chem. 1970 Sep 25;245(18):4724–4731. [PubMed] [Google Scholar]
  10. DAVISON A. N., SANDLER M. Inhibition of 5-hydroxytryptophan decarboxylase by phenylalanine metabolites. Nature. 1958 Jan 18;181(4603):186–187. doi: 10.1038/181186b0. [DOI] [PubMed] [Google Scholar]
  11. Gallagher B. B. The effect of phenylpyruvate on oxidative-phosphorylation in brain mitochondria. J Neurochem. 1969 Jul;16(7):1071–1076. doi: 10.1111/j.1471-4159.1969.tb05951.x. [DOI] [PubMed] [Google Scholar]
  12. Gallagher B. B. The influence of tyrosine, phenylpyruvate and vitamin B 6 upon seizure thresholds. J Neurochem. 1971 Jun;18(6):799–808. doi: 10.1111/j.1471-4159.1971.tb12009.x. [DOI] [PubMed] [Google Scholar]
  13. Gerstl B., Malamud N., Eng L. F., Hayman R. B. Lipid alterations in human brains in phenylketonuria. Neurology. 1967 Jan;17(1):51–passim. doi: 10.1212/wnl.17.1.51. [DOI] [PubMed] [Google Scholar]
  14. HARTMAN W. J., AKAWIE R. I., CLARK W. G. Competitive inhibition of 3, 4-dihydroxyphenylalanine (DOPA) decarboxylase in vitro. J Biol Chem. 1955 Oct;216(2):507–529. [PubMed] [Google Scholar]
  15. HOWELL R. K., LEE M. Influence of alpha-ketoacids on the respiration of brain in vitro. Proc Soc Exp Biol Med. 1963 Jul;113:660–663. doi: 10.3181/00379727-113-28456. [DOI] [PubMed] [Google Scholar]
  16. Itoh T. Effects of sodium phenylpyruvate on amino acid formation in brain. Can J Biochem. 1965 Jul;43(7):835–840. doi: 10.1139/o65-095. [DOI] [PubMed] [Google Scholar]
  17. JERVIS G. A. Phenylpyruvic oligophrenia deficiency of phenylalanine-oxidizing system. Proc Soc Exp Biol Med. 1953 Mar;82(3):514–515. [PubMed] [Google Scholar]
  18. JERVIS G. A. Studies on phenylpyruvic oligophrenia; phenylpyruvic acid content on blood. Proc Soc Exp Biol Med. 1952 Dec;81(3):715–720. doi: 10.3181/00379727-81-19998. [DOI] [PubMed] [Google Scholar]
  19. Jervis G. A., Drejza E. J. Phenylketonuria: blood levels of phenylpyruvic and ortho-hydroxyphenylacetic acids. Clin Chim Acta. 1966 Apr;13(4):435–441. doi: 10.1016/0009-8981(66)90234-8. [DOI] [PubMed] [Google Scholar]
  20. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  21. MITOMA C., AULD R. M., UDENFRIEND S. On the nature of enzymatic defect in phenylpyruvic oligophrenia. Proc Soc Exp Biol Med. 1957 Apr;94(4):634–635. doi: 10.3181/00379727-94-23034. [DOI] [PubMed] [Google Scholar]
  22. Menkes J. H. Cerebral lipids in phenylketonuria. Pediatrics. 1966 Jun;37(6):967–978. [PubMed] [Google Scholar]
  23. Moellering H., Gruber W. Determination of citrate with citrate lyase. Anal Biochem. 1966 Dec;17(3):369–376. doi: 10.1016/0003-2697(66)90172-2. [DOI] [PubMed] [Google Scholar]
  24. O'Brien D., Ibbot F. A. Effect of prolonged phenylalanine loading on the free amino-acid and lipid content of the infant monkey brain. Dev Med Child Neurol. 1966 Dec;8(6):724–728. doi: 10.1111/j.1469-8749.1966.tb01832.x. [DOI] [PubMed] [Google Scholar]
  25. Patel M. S., Hanson R. W. Carboxylation of pyruvate by isolated rat adipose tissue mitochondria. J Biol Chem. 1970 Mar 25;245(6):1302–1310. [PubMed] [Google Scholar]
  26. Shah S. N., Peterson N. A., McKean C. M. Cerebral lipid metabolism in experimental hyperphenylalaninaemia: incorporation of 14C-labelled glucose into total lipids. J Neurochem. 1970 Feb;17(2):279–284. doi: 10.1111/j.1471-4159.1970.tb02211.x. [DOI] [PubMed] [Google Scholar]
  27. Swaiman K. F., Hosfield W. B., Lemieux B. Elevated plasma phenylalanine concentration and lysine incorporation into ribosomal protein of developing brain. J Neurochem. 1968 Jul;15(7):687–690. doi: 10.1111/j.1471-4159.1968.tb08968.x. [DOI] [PubMed] [Google Scholar]
  28. UTTER M. F., KEECH D. B. PYRUVATE CARBOXYLASE. I. NATURE OF THE REACTION. J Biol Chem. 1963 Aug;238:2603–2608. [PubMed] [Google Scholar]
  29. WALLACE H. W., MOLDAVE K., MEISTER A. Studies on conversion of phenylalanine to tyrosine in phenylpyruvic oligophrenia. Proc Soc Exp Biol Med. 1957 Apr;94(4):632–633. doi: 10.3181/00379727-94-23033. [DOI] [PubMed] [Google Scholar]
  30. Weber G., Glazer R. I., Ross R. A. Regulation of human and rat brain metabolism: inhibitory action of phenylalanine and phenylpyruvate on glycolysis, protein, lipid, DNA, and RNA metabolism. Adv Enzyme Regul. 1970;8:13–36. doi: 10.1016/0065-2571(70)90006-3. [DOI] [PubMed] [Google Scholar]
  31. Wimhurst J. M., Manchester K. L. Some aspects of the kinetics of rat liver pyruvate carboxylase. Biochem J. 1970 Nov;120(1):79–93. doi: 10.1042/bj1200079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yuwiler A., Geller E. Brain serotonin changes in phenylalanine-fed rats: synthesis storage and degradation. J Neurochem. 1969 Jun;16(3):999–1005. doi: 10.1111/j.1471-4159.1969.tb08990.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES