Abstract
1. The development of pyruvate dehydrogenase and citrate synthase activity in rat brain mitochondria was studied. Whereas the citrate synthase activity starts to increase at about 8 days after birth, that of pyruvate dehydrogenase starts to increase at about 15 days. Measurements of the active proportion of pyruvate dehydrogenase during development were also made. 2. The ability of rat brain mitochondria to oxidize pyruvate follows a similar developmental pattern to that of the pyruvate dehydrogenase. However, the ability to oxidize 3-hydroxybutyrate shows a different developmental pattern (maximal at 20 days and declining by half in the adult), which is compatible with the developmental pattern of the ketone-body-utilizing enzymes. 3. The developmental pattern of both the soluble and the mitochondrially bound hexokinase of rat brain was studied. The total brain hexokinase activity increases markedly at about 15 days, which is mainly due to an increase in activity of the mitochondrially bound form, and reaches the adult situation (approx. 70% being mitochondrial) at about 30 days after birth. 4. The release of the mitochondrially bound hexokinase under different conditions by glucose 6-phosphate was studied. There was insignificant release of the bound hexokinase in media containing high KCl concentrations by glucose 6-phosphate, but in sucrose media half-maximal release of hexokinase was achieved by 70μm-glucose 6-phosphate 5. The production of glucose 6-phosphate by brain mitochondria in the presence of Mg2++glucose was demonstrated, together with the inhibition of this by atractyloside. 6. The results are discussed with respect to the possible biological significance of the similar developmental patterns of pyruvate dehydrogenase and the mitochondrially bound kinases, particularly hexokinase, in the brain. It is suggested that this association may be a mechanism for maintaining an efficient and active aerobic glycolysis which is necessary for full neural expression.
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Selected References
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- Bachelard H. S. The subcellular distribution and properties of hexokinases in the guinea-pig cerebral cortex. Biochem J. 1967 Jul;104(1):286–292. doi: 10.1042/bj1040286. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHANCE B., WILLIAMS G. R. The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem. 1956;17:65–134. doi: 10.1002/9780470122624.ch2. [DOI] [PubMed] [Google Scholar]
- Clark J. B., Land J. M. Differential effects of 2-oxo acids on pyruvate utilization and fatty acid synthesis in rat brain. Biochem J. 1974 Apr;140(1):25–29. doi: 10.1042/bj1400025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Cotman C. W., Matthews D. A. Synaptic plasma membranes from rat brain synaptosomes: isolation and partial characterization. Biochim Biophys Acta. 1971 Dec 3;249(2):380–394. doi: 10.1016/0005-2736(71)90117-9. [DOI] [PubMed] [Google Scholar]
- Cremer J. E., Heath D. F. The estimation of rates of utilization of glucose and ketone bodies in the brain of the suckling rat using compartmental analysis of isotopic data. Biochem J. 1974 Sep;142(3):527–544. doi: 10.1042/bj1420527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cremer J. E., Teal H. M. The activity of pyruvate dehydrogenase in rat brain during postnatal development. FEBS Lett. 1974 Feb 1;39(1):17–20. doi: 10.1016/0014-5793(74)80006-2. [DOI] [PubMed] [Google Scholar]
- ELLMAN G. L., COURTNEY K. D., ANDRES V., Jr, FEATHER-STONE R. M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961 Jul;7:88–95. doi: 10.1016/0006-2952(61)90145-9. [DOI] [PubMed] [Google Scholar]
- Font B., Vial C., Gautheron D. C. Intracellular and submitochondrial localization of pig heart hexokinase. FEBS Lett. 1975 Aug 1;56(1):24–29. doi: 10.1016/0014-5793(75)80103-7. [DOI] [PubMed] [Google Scholar]
- Gregson N. A., Williams P. L. A comparative study of brain and liver mitochondria from new-born and adult rats. J Neurochem. 1969 Apr;16(4):617–626. doi: 10.1111/j.1471-4159.1969.tb06861.x. [DOI] [PubMed] [Google Scholar]
- Hawkins R. A., Williamson D. H., Krebs H. A. Ketone-body utilization by adult and suckling rat brain in vivo. Biochem J. 1971 Mar;122(1):13–18. doi: 10.1042/bj1220013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hernandez A., Crane R. K. Association of heart hexokinase with subcellular structure. Arch Biochem Biophys. 1966 Jan;113(1):223–229. doi: 10.1016/0003-9861(66)90176-7. [DOI] [PubMed] [Google Scholar]
- Holtzman D., Moore C. L. Oxidative phosphorylation in immature rat brain mitochondria. Biol Neonate. 1973;22(3):230–242. doi: 10.1159/000240556. [DOI] [PubMed] [Google Scholar]
- Hucho F. The pyruvate dehydrogenase multienzyme complex. Angew Chem Int Ed Engl. 1975 Sep;14(9):591–601. doi: 10.1002/anie.197505911. [DOI] [PubMed] [Google Scholar]
- JOHNSON M. K., WHITTAKER V. P. LACTATE DEHYDROGENASE AS A CYTOPLASMIC MARKER IN BRAIN. Biochem J. 1963 Sep;88:404–409. doi: 10.1042/bj0880404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacobs H., Heldt H. W., Klingenberg M. High activity of creatine kinase in mitochondria from muscle and brain and evidence for a separate mitochondrial isoenzyme of creatine kinase. Biochem Biophys Res Commun. 1964 Aug 11;16(6):516–521. doi: 10.1016/0006-291x(64)90185-8. [DOI] [PubMed] [Google Scholar]
- Jacobus W. E., Lehninger A. L. Creatine kinase of rat heart mitochondria. Coupling of creatine phosphorylation to electron transport. J Biol Chem. 1973 Jul 10;248(13):4803–4810. [PubMed] [Google Scholar]
- Jowett M., Quastel J. H. Studies in fat metabolism: The formation and breakdown of acetoacetic acid in animal tissues. Biochem J. 1935 Sep;29(9):2181–2191. doi: 10.1042/bj0292181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KUHLMAN R. E., LOWRY O. H. Quantitative histochemical changes during the development of the rat cerebral cortex. J Neurochem. 1956 Dec;1(2):173–180. doi: 10.1111/j.1471-4159.1956.tb12070.x. [DOI] [PubMed] [Google Scholar]
- Klee C. B., Sokoloff L. Changes in D(--)-beta-hydroxybutyric dehydrogenase activity during brain maturation in the rat. J Biol Chem. 1967 Sep 10;242(17):3880–3883. [PubMed] [Google Scholar]
- Kraus H., Schlenker S., Schwedesky D. Developmental changes of cerebral ketone body utilization in human infants. Hoppe Seylers Z Physiol Chem. 1974 Feb;355(2):164–170. doi: 10.1515/bchm2.1974.355.1.164. [DOI] [PubMed] [Google Scholar]
- 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]
- Lai J. C., Clark J. B. Preparation and properties of mitochondria derived from synaptosomes. Biochem J. 1976 Feb 15;154(2):423–432. doi: 10.1042/bj1540423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDonnell P. C., Greengard O. Enzymes in intracellular organelles of adult and developing rat brain. Arch Biochem Biophys. 1974 Aug;163(2):644–655. doi: 10.1016/0003-9861(74)90525-6. [DOI] [PubMed] [Google Scholar]
- Middleton B. The acetoacetyl-coenzyme A thiolases of rat brain and their relative activities during postnatal development. Biochem J. 1973 Apr;132(4):731–737. doi: 10.1042/bj1320731. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Owen O. E., Morgan A. P., Kemp H. G., Sullivan J. M., Herrera M. G., Cahill G. F., Jr Brain metabolism during fasting. J Clin Invest. 1967 Oct;46(10):1589–1595. doi: 10.1172/JCI105650. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Page M. A., Krebs H. A., Williamson D. H. Activities of enzymes of ketone-body utilization in brain and other tissues of suckling rats. Biochem J. 1971 Jan;121(1):49–53. doi: 10.1042/bj1210049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rose I. A., Warms J. V. Mitochondrial hexokinase. Release, rebinding, and location. J Biol Chem. 1967 Apr 10;242(7):1635–1645. [PubMed] [Google Scholar]
- Saks V. A., Chernousova G. B., Vetter R., Smirnov V. N., Chazov E. I. Kinetic properties and the functional role of particulate MM-isoenzyme of creatine phosphokinase bound to heart muscle myofibrils. FEBS Lett. 1976 Mar 1;62(3):293–296. doi: 10.1016/0014-5793(76)80078-6. [DOI] [PubMed] [Google Scholar]
- Siess E., Wittmann J., Wieland O. Interconversion and kinetic properties of pyruvate dehydrogenase from brain. Hoppe Seylers Z Physiol Chem. 1971 Mar;352(3):447–452. doi: 10.1515/bchm2.1971.352.1.447. [DOI] [PubMed] [Google Scholar]
- Tuttle J. P., Wilson J. E. Brain hexokinase: a kinetic comparison of soluble and particulate forms. Biochim Biophys Acta. 1970 Jul 15;212(1):185–188. doi: 10.1016/0005-2744(70)90195-6. [DOI] [PubMed] [Google Scholar]
- Volpe J. J., Kishimoto Y. Fatty acid synthetase of brain: development, influence of nutritional and hormonal factors and comparison with liver enzyme. J Neurochem. 1972 Mar;19(3):737–753. doi: 10.1111/j.1471-4159.1972.tb01389.x. [DOI] [PubMed] [Google Scholar]
- Wilbur D. O., Patel M. S. Development of mitochondrial pyruvate metabolism in rat brain. J Neurochem. 1974 May;22(5):709–715. doi: 10.1111/j.1471-4159.1974.tb04284.x. [DOI] [PubMed] [Google Scholar]
- Wilson J. E. Brain hexokinase. A proposed relation between soluble-particulate distribution and activity in vivo. J Biol Chem. 1968 Jul 10;243(13):3640–3647. [PubMed] [Google Scholar]
- Wilson J. E. The localization of latent brain hexokinase on synaptosomal mitochondria. Arch Biochem Biophys. 1972 May;150(1):96–104. doi: 10.1016/0003-9861(72)90015-x. [DOI] [PubMed] [Google Scholar]
- Winick M. Nutrition and nerve cell growth. Fed Proc. 1970 Jul-Aug;29(4):1510–1515. [PubMed] [Google Scholar]