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Journal of Inherited Metabolic Disease

Erschienen in:

01.01.2012 | Branched-Chain Amino Acids

Interrupting the mechanisms of brain injury in a model of maple syrup urine disease encephalopathy

verfasst von: William J. Zinnanti, Jelena Lazovic

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 1/2012

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Abstract

Maple syrup urine disease (MSUD) was first recognized as an inherited lethal encephalopathy beginning in the first week of life and associated with an unusual odor in the urine of affected children. It was later confirmed as a deficiency of branched-chain keto acid dehydrogenase (BCKDH), which is the second step in branched-chain amino acid (BCAA) breakdown. MSUD is characterized by BCAA and branched-chain keto acid (BCKA) accumulation. BCAAs are essential amino acids and powerful metabolic signals with severe consequences of both deprivation and accumulation. Treatment requires life-long dietary restriction and monitoring of BCAAs. However, despite excellent compliance, children commonly suffer metabolic decompensation during intercurrent illness resulting in life-threatening cerebral edema and dysmyelination. The mechanisms underlying brain injury have been poorly understood. Recent studies using newly developed mouse models of both classic and intermediate MSUD have yielded insight into the consequences of rapid BCAA accumulation. Additionally, these models have been used to test preliminary treatments aimed at competing with blood-brain barrier transport of BCAA using norleucine. Assessment of biochemical changes with and without treatment suggests different roles for BCAA and BCKA in the mechanism of brain injury.

Chuang DT, Shih VE (2001) Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 1971–2005

Chuang DT, Ku LS et al (1982) Biochemical basis of thiamin-responsive maple syrup urine disease. Trans Assoc Am Physicians 95:196–204PubMed

Cremer JE (1982) Substrate utilization and brain development. J Cereb Blood Flow Metab 2(4):394–407PubMedCrossRef

Crome L, Dutton G et al (1961) Maple syrup urine disease. J Pathol Bacteriol 81:379–384PubMedCrossRef

Dancis J, Hutzler J et al (1960) Metabolism of the white blood cells in maple-syrup-urine disease. Biochim Biophys Acta 43:342–343PubMedCrossRef

Daniel PM, Pratt OE et al (1977) The mechanism by which glucagon induces the release of amino acids from muscle and its relevance to fasting. Proc R Soc Lond B Biol Sci 196(1124):347–365PubMedCrossRef

Dhopeshwarkar GA, Subramanian C (1979) Lipogenesis in the developing brain: utilization of radioactive leucine, isoleucine, octanoic acid and beta-hydroxybutyric acid. Lipids 14(1):47–51PubMedCrossRef

Dodd PR, Williams SH et al (1992) Glutamate and gamma-aminobutyric acid neurotransmitter systems in the acute phase of maple syrup urine disease and citrullinemia encephalopathies in newborn calves. J Neurochem 59(2):582–590PubMedCrossRef

Donnell GN, Lieberman E et al (1967) Hypoglycemia in maple syrup urine disease. Am J Dis Child 113(1):60–63PubMed

Garcia-Espinosa MA, Wallin R et al (2007) Widespread neuronal expression of branched-chain aminotransferase in the CNS: implications for leucine/glutamate metabolism and for signaling by amino acids. J Neurochem 100(6):1458–1468PubMed

Hall TR, Wallin R et al (1993) Branched chain aminotransferase isoenzymes. Purification and characterization of the rat brain isoenzyme. J Biol Chem 268(5):3092–3098PubMed

Harper PA, Healy PJ et al (1990) Maple syrup urine disease (branched chain ketoaciduria). Am J Pathol 136(6):1445–1447PubMed

Harris RA, Popov KM et al (1994) Regulation of branched-chain amino acid catabolism. J Nutr 124(8 Suppl):1499S–1502SPubMed

Haymond MW, Karl IE et al (1973) Hypoglycemia and maple syrup urine disease: defective gluconeogenesis. Pediatr Res 7(5):500–508PubMedCrossRef

Homanics GE, Skvorak K et al (2006) Production and characterization of murine models of classic and intermediate maple syrup urine disease. BMC Med Genet 7:33PubMedCrossRef

Ichihara A, Koyama E (1966) Transaminase of branched chain amino acids. I. Branched chain amino acids-alpha-ketoglutarate transaminase. J Biochem 59(2):160–169PubMed

Islam MM, Wallin R et al (2007) A novel branched-chain amino acid metabolon. Protein-protein interactions in a supramolecular complex. J Biol Chem 282(16):11893–11903PubMedCrossRef

Kamei A, Takashima S et al (1992) Abnormal dendritic development in maple syrup urine disease. Pediatr Neurol 8(2):145–147PubMedCrossRef

Kimball SR, Jefferson LS (2006) Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. J Nutr 136(1 Suppl):227S–231SPubMed

Kistner A, Gossen M et al (1996) Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci USA 93(20):10933–10938PubMedCrossRef

Lieth E, LaNoue KF et al (2001) Nitrogen shuttling between neurons and glial cells during glutamate synthesis. J Neurochem 76(6):1712–1723PubMedCrossRef

McKean CM, Boggs DE et al (1968) The influence of high phenylalanine and tyrosine on the concentrations of essential amino acids in brain. J Neurochem 15(3):235–241PubMedCrossRef

Menkes JH (1959) Maple syrup disease; isolation and identification of organic acids in the urine. Pediatrics 23(2):348–353PubMed

Menkes JH (1962) Maple syrup disease and other disorders of keto acid metabolism. Res Publ Assoc Res Nerv Ment Dis 40:69–93PubMed

Menkes JH, Hurst PL et al (1954) A new syndrome: progressive familial infantile cerebral dysfunction associated with an unusual urinary substance. Pediatrics 14(5):462–467PubMed

Milne JL, Shi D et al (2002) Molecular architecture and mechanism of an icosahedral pyruvate dehydrogenase complex: a multifunctional catalytic machine. EMBO J 21(21):5587–5598PubMedCrossRef

Mitsubuchi H, Matsuda I et al (1992) Gene analysis of Mennonite maple syrup urine disease kindred using primer-specified restriction map modification. J Inherit Metab Dis 15(2):181–187PubMedCrossRef

Morton DH, Strauss KA et al (2002) Diagnosis and treatment of maple syrup disease: a study of 36 patients. Pediatrics 109(6):999–1008PubMedCrossRef

Ng VL, Fecteau A et al (2008) Outcomes of 5-year survivors of pediatric liver transplantation: report on 461 children from a North American multicenter registry. Pediatrics 122(6):e1128–e1135PubMedCrossRef

Nyhan WL, Rice-Kelts M et al (1998) Treatment of the acute crisis in maple syrup urine disease. Arch Pediatr Adolesc Med 152(6):593–598PubMed

Patel MS (1974) Inhibition by the branched-chain 2-oxo acids of the 2-oxoglutarate dehydrogenase complex in developing rat and human brain. Biochem J 144(1):91–97PubMed

Patel MS, Auerbach VH et al (1973) Effect of the branched-chain alpha-keto acids on pyruvate metabolism by homogenates of human brain. J Neurochem 20(6):1793–1796PubMedCrossRef

Prensky AL, Moser HW (1966) Brain lipids, proteolipids, and free amino acids in maple syrup urine disease. J Neurochem 13(9):863–874PubMedCrossRef

Reed LJ (2001) A trail of research from lipoic acid to alpha-keto acid dehydrogenase complexes. J Biol Chem 276(42):38329–38336PubMedCrossRef

Riviello JJ Jr, Rezvani I et al (1991) Cerebral edema causing death in children with maple syrup urine disease. J Pediatr 119(1 Pt 1):42–45PubMed

Rocha DM, Faloona GR et al (1972) Glucagon-stimulating activity of 20 amino acids in dogs. J Clin Invest 51(9):2346–2351PubMedCrossRef

Schonberger S, Schweiger B et al (2004) Dysmyelination in the brain of adolescents and young adults with maple syrup urine disease. Mol Genet Metab 82(1):69–75PubMedCrossRef

Sgaravatti AM, Rosa RB et al (2003) Inhibition of brain energy metabolism by the alpha-keto acids accumulating in maple syrup urine disease. Biochim Biophys Acta 1639(3):232–238PubMed

She P, Reid TM et al (2007) Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab 6(3):181–194PubMedCrossRef

Shestopalov AI, Kristal BS (2007) Branched chain keto-acids exert biphasic effects on alpha-ketoglutarate-stimulated respiration in intact rat liver mitochondria. Neurochem Res 32(4–5):947–951PubMedCrossRef

Silberman J, Dancis J et al (1961) Neuropathological observations in maple syrup urine disease: branched-chain ketoaciduria. Arch Neurol 5:351–363PubMedCrossRef

Strauss KA, Mazariegos GV et al (2006) Elective liver transplantation for the treatment of classical maple syrup urine disease. Am J Transplant 6(3):557–564PubMedCrossRef

Strauss KA, Wardley B et al (2010) Classical maple syrup urine disease and brain development: principles of management and formula design. Mol Genet Metab 99(4):333–345PubMedCrossRef

Sweatt AJ, Garcia-Espinosa MA et al (2004) Branched-chain amino acids and neurotransmitter metabolism: expression of cytosolic branched-chain aminotransferase (BCATc) in the cerebellum and hippocampus. J Comp Neurol 477(4):360–370PubMedCrossRef

Tews JK, Repa JJ et al (1991) Branched-chain and other amino acids in tissues of rats fed leucine-limiting amino acid diets containing norleucine. J Nutr 121(3):364–378PubMed

Zinnanti WJ, Lazovic J et al (2007) Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I. J Clin Invest 117(11):3258–3270PubMedCrossRef

Zinnanti WJ, Lazovic J et al (2009) Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease. Brain 132(Pt 4):903–918PubMed

Titel: Interrupting the mechanisms of brain injury in a model of maple syrup urine disease encephalopathy
verfasst von: William J. Zinnanti
Jelena Lazovic
Publikationsdatum: 01.01.2012
Verlag: Springer Netherlands
Erschienen in: Journal of Inherited Metabolic Disease / Ausgabe 1/2012
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-011-9333-5

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