Abstract
Leucine and protein metabolism were studied using stable isotope techniques in 6-year-old twins with 3-hydroxy-3-methylglutaric aciduria during acute metabolic decompensation. The decompensation was preceded by prolonged fasting in twin 1 and by an upper respiratory infection in twin 2. Twin 2 was also studied when well (control study). During infection, leucine oxidation (36 μmol/kg per hour), protein catabolism (6.0 g/kg per day) and urinary excretion of major leucine metabolites (104 μmol/kg per hour) were all increased compared with the control study (16 μmol/kg per hour, 4.7 g/kg per day and 28 μmol/kg per hour respectively). During fasting, leucine oxidation (18 μmol/kg per hour) was unchanged and protein catabolism (4.1 g/kg per day) was decreased despite substantially increased urinary metabolite excretion (87 μmol/kg per hour) compared with the control study. These results indicate that protein mobilisation and leucine oxidation played important roles in metabolic decompensation during infection but not during fasting. It is likely that the increased metabolite excretion during fasting arose primarily from fatty acid catabolism, indicating the importance of this substrate in metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria.
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Abbreviations
- HMG CoA lyase:
-
3-hydroxy-3-methylglutaryl CoA lyase
- KIC:
-
alpha-ketoisocaproic acid
References
Dasouki M, Buchanan D, Mercer N, Gibson KM, Theone J (1987) 3-Hydroxy-3-methylglutaric aciduria: response to carnitine therapy and fat and leucine restricion. J Inherited Metab Dis 10:142–146
Faull KF, Bolton P, Halpern P, Hammond J, Danks DM, Hähnel R, Wilkinson SP, Wysocki SJ, Masters PL (1976) Patient with defect in leucine metabolism. N Engl J Med 294:1013
Ford GC, Cheng KN, Halliday D (1985) Analysis of [1-13C]leucine and [13C]KIC in plasma by capillary gas chromatography/mass spectrometry in protein turnover studies. Biomed Mass Spectrom 12:432–436
Garrow JS, Webster JD (1986) A computer-controlled indirect calorimeter for the measurement of energy expenditure in one or two subjects simulaneously. Hum Nutr Clin Nutr 40C:315–321
Gibson KM, Breuer J, Nyhan WL (1988) 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. Eur J Pediatr 148:180–186
Gibson KM, Breuer J, Kaiser K, Nyhan WL, McCoy EE, Ferriera P, Greene CL, Blitzer MG, Shapira E, Reverte F, Conde C, Bagnell P, Cole DEC (1988) 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: report of five new cases. J Inherited Metab Dis 11:76–87
Leonard JV, Seakins JW, Griffin NK (1979) Beta-hydroxy-beta-methylglutaricaciduria presenting as Reyes syndrome. Lancet I:680
Matthews DE, Motil KJ, Rohrbaugh DK, Burke JF, Young VR, Bier DM (1980) Measurement of leucine metabolism in man from a primed continuous infusion of L-[1-13C]leucine. Am J Physiol 238:E473–479
Matthews DE, Schwarz HP, Yang RD, Motil KJ, Young VR, Bier DM (1982) Relationship of plasma leucine and α-ketoisocaproic acid during a L-[1-13C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment. Metabolism 31:1105–1112
McGarry JD, Foster DW (1980) Regulating of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem 49:395–420
Munro HN, Fleck A (1969) Analysis of tissues and body fluids for nitrogenous constituents. In: Munro HN (ed) Mammalian protein metabolism. Academic Press, New York 3:423–525
Robinson BH, Oei J, Sherwood WG, Slyper AH, Heininger J, Mamer OA (1980) Hydroxymethylglutaryl CoA lyase deficiency: features resembling Reye syndrome. Neurology 30:714–718
Rosenberg LE (1983) Disorders of propionate and methylmalonate metabolism. In: Stanbury JB, Wyngaarden JB, Frederickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 474–497
Schutgens RB, Heymans H, Ketel A, Veder HA, Duran M, Ketting D, Wadman SK (1979) Lethal hypoglycaemia in a child with a deficiency of 3-hydroxy-3-methylglutarylcoenzyme A lyase. J Pediatr 94:89–91
Schwenk WF, Berg PJ, Beaufrere B, Miles JM, Haymond MW (1983) Use of t-butyldimethylsilylation in the gas chromatographic/mass spectrometric analysis of physiologic compounds found in plasma using electron-impact ionisation. Anal Biochem 141:101–109
Stacey TE, Sousa C de, Tracey BM, Whitelaw A, Mistry J, Timbrell P, Chalmers RA (1985) Dizygotic twins with 3-hydroxy-3-methylglutaric aciduria: unusual presentation, family studies and dietary management. Eur J Pediatr 144:177–181
Thompson GN, Pacy PJ, Merritt H, Ford GC, Read MA, Cheng KN, Halliday D (1989) Rapid measurement of whole body and forearm protein turnover using a phenylalanine model. Am J Physiol 256:E631–9
Wanders RJA, Schutgens RBH, Zoeters PHM (1988) 3-Hydroxy-3-methylglutaryl-CoA lyase in human skin fibroblasts: study of its properties and deficient activity in 3-hydroxy-3-methylglutaric aciduria patients using a simple spectrophotometric method. Clin Chim Acta 171:95–102
Waterlow JC, Garlick PJ, Millward DJ (1978) Protein turnover in mammalian tissues and in the whole body. North-Holland, Amsterdam, pp 179–249
Wilson WG, Cass MB, Sovik O, Gibson KM, Sweetman L (1984) A child with acute pancreatitis due to 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. Eur J Pediatr 142:289–291
Wysocki SJ, Hahnel R (1986) 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: a review. J Inherited Metab Dis 9:225–233
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Thompson, G.N., Chalmers, R.A. & Halliday, D. The contribution of protein catabolism to metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria. Eur J Pediatr 149, 346–350 (1990). https://doi.org/10.1007/BF02171564
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DOI: https://doi.org/10.1007/BF02171564