Systemic deficiency of the first component of the pyruvate dehydrogenase complex

D. S. Kerr, L. Ho, Cheston Berlin, K. F. Lanoue, J. Towfighi, C. L. Hoppel, M. M. Lusk, C. M. Gondek, M. S. Patel

Research output: Contribution to journalArticle

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Abstract

An infant with lactic acidosis and developmental delay had neuropathological changes consistent with Leigh's necrotizing encephalomyelopathy. Total pyruvate dehydrogenase complex (PDC) activity was low relative to controls in lymphocytes (0.2 versus 1.9 ± 0.6 SD nmol/min/mg protein) and cultured skin fibroblasts (0.9 versus 2.7 ± 1.0). Liver, muscle, heart, and kidney mitochondria oxidized several substrates normally, but did not oxidize pyruvate. PDC activity was absent in these mitochondria (0.1 versus 9.8 ± 4.2 in liver and 0.7 versus 75 ± 26 in muscle) and was very low in all tissue homogenates. Activity of the first component was low in liver mitochondria, whereas activities of the second and third components were normal. Western blot analysis of tissue proteins showed normal amounts of second and third component of PDC but undetectable to trace amounts of both α and β subunits of the first component of PDC in liver, brain, kidney, heart, and skin fibroblasts. Thus, profound systemic deficiency of PDC was due to lack of both subunit proteins of the first component of PDC.

Original languageEnglish (US)
Pages (from-to)312-318
Number of pages7
JournalPediatric Research
Volume22
Issue number3
DOIs
StatePublished - Jan 1 1987

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Pyruvate Dehydrogenase Complex
Liver
Pyruvate Dehydrogenase Complex Deficiency Disease
Fibroblasts
Kidney
Heart Mitochondria
Muscles
Lactic Acidosis
Skin
Liver Mitochondrion
Protein Subunits
Pyruvic Acid
Mitochondria
Proteins
Western Blotting
Lymphocytes
Brain

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Kerr, D. S., Ho, L., Berlin, C., Lanoue, K. F., Towfighi, J., Hoppel, C. L., ... Patel, M. S. (1987). Systemic deficiency of the first component of the pyruvate dehydrogenase complex. Pediatric Research, 22(3), 312-318. https://doi.org/10.1203/00006450-198709000-00015
Kerr, D. S. ; Ho, L. ; Berlin, Cheston ; Lanoue, K. F. ; Towfighi, J. ; Hoppel, C. L. ; Lusk, M. M. ; Gondek, C. M. ; Patel, M. S. / Systemic deficiency of the first component of the pyruvate dehydrogenase complex. In: Pediatric Research. 1987 ; Vol. 22, No. 3. pp. 312-318.
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Kerr, DS, Ho, L, Berlin, C, Lanoue, KF, Towfighi, J, Hoppel, CL, Lusk, MM, Gondek, CM & Patel, MS 1987, 'Systemic deficiency of the first component of the pyruvate dehydrogenase complex', Pediatric Research, vol. 22, no. 3, pp. 312-318. https://doi.org/10.1203/00006450-198709000-00015

Systemic deficiency of the first component of the pyruvate dehydrogenase complex. / Kerr, D. S.; Ho, L.; Berlin, Cheston; Lanoue, K. F.; Towfighi, J.; Hoppel, C. L.; Lusk, M. M.; Gondek, C. M.; Patel, M. S.

In: Pediatric Research, Vol. 22, No. 3, 01.01.1987, p. 312-318.

Research output: Contribution to journalArticle

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AU - Kerr, D. S.

AU - Ho, L.

AU - Berlin, Cheston

AU - Lanoue, K. F.

AU - Towfighi, J.

AU - Hoppel, C. L.

AU - Lusk, M. M.

AU - Gondek, C. M.

AU - Patel, M. S.

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N2 - An infant with lactic acidosis and developmental delay had neuropathological changes consistent with Leigh's necrotizing encephalomyelopathy. Total pyruvate dehydrogenase complex (PDC) activity was low relative to controls in lymphocytes (0.2 versus 1.9 ± 0.6 SD nmol/min/mg protein) and cultured skin fibroblasts (0.9 versus 2.7 ± 1.0). Liver, muscle, heart, and kidney mitochondria oxidized several substrates normally, but did not oxidize pyruvate. PDC activity was absent in these mitochondria (0.1 versus 9.8 ± 4.2 in liver and 0.7 versus 75 ± 26 in muscle) and was very low in all tissue homogenates. Activity of the first component was low in liver mitochondria, whereas activities of the second and third components were normal. Western blot analysis of tissue proteins showed normal amounts of second and third component of PDC but undetectable to trace amounts of both α and β subunits of the first component of PDC in liver, brain, kidney, heart, and skin fibroblasts. Thus, profound systemic deficiency of PDC was due to lack of both subunit proteins of the first component of PDC.

AB - An infant with lactic acidosis and developmental delay had neuropathological changes consistent with Leigh's necrotizing encephalomyelopathy. Total pyruvate dehydrogenase complex (PDC) activity was low relative to controls in lymphocytes (0.2 versus 1.9 ± 0.6 SD nmol/min/mg protein) and cultured skin fibroblasts (0.9 versus 2.7 ± 1.0). Liver, muscle, heart, and kidney mitochondria oxidized several substrates normally, but did not oxidize pyruvate. PDC activity was absent in these mitochondria (0.1 versus 9.8 ± 4.2 in liver and 0.7 versus 75 ± 26 in muscle) and was very low in all tissue homogenates. Activity of the first component was low in liver mitochondria, whereas activities of the second and third components were normal. Western blot analysis of tissue proteins showed normal amounts of second and third component of PDC but undetectable to trace amounts of both α and β subunits of the first component of PDC in liver, brain, kidney, heart, and skin fibroblasts. Thus, profound systemic deficiency of PDC was due to lack of both subunit proteins of the first component of PDC.

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