Differential inhibition by hyperammonemia of the electron transport chain enzymes in synaptosomes and nonsynaptic mitochondria in ornithine transcarbamylase-deficient spf-Mice: Restoration by acetyl-L-carnitine

Karim Qureshi, K. V.Rama Rao, Ijaz A. Qureshi

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Sparse-fur (spf) mouse is the ideal animal model to study the neuropathology of congenital ornithine transcarbamylase (OTC) deficiency. Our current hypothesis implies that an ammonia-induced depletion of energy metabolism in the spf mouse, could be due to a reduction in the activities of the enzymes of the electron transport chain and a treatment with acetyl-L- carnitine could normalize this abnormality. We also hypothesized that there might be a differential degree of inhibition in synaptosomal and non-synaptic mitochondria, for the enzymes of the electron transport chain, caused by congenital hyperammonemia. We have therefore measured the activities of NADH- cytochrome C oxidoreductase, succinate cytochrome C oxidoreductase and cytochrome C oxidase in synaptosomes and non-synaptic mitochondria, isolated from spf mice and CD-1 controls with and without acetyl-L-carnitine treatment. Our results indicate a significant reduction (19-34%) in the activities of these complexes in synaptosomes in untreated spf mice, whereas in non-synaptic mitochondria, there was a tendency for the activities to decrease. Acetyl-L-carnitine treatment enhanced these activities (1564%) for all the three enzyme complexes and its effect was more prominent on succinate cytochrome C oxidoreductase activity (64%). These studies point out that: (a) ammonia-induced disturbances in the energy metabolism could be more pronounced in neuronal mitochondria, and (b) the effect of acetyl-L-carnitine on the restoration of cerebral ATP in hyperammonemia could be through an enhancement of the activities of various electron transport chain enzymes.

Original languageEnglish (US)
Pages (from-to)855-861
Number of pages7
JournalNeurochemical Research
Volume23
Issue number6
DOIs
StatePublished - 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • Acetyl-L-carnitine
  • Brain
  • Electron transport chain
  • Non-synaptic mitochondria
  • Ornithine transcarbamylase deficiency
  • Synaptosomes

Fingerprint Dive into the research topics of 'Differential inhibition by hyperammonemia of the electron transport chain enzymes in synaptosomes and nonsynaptic mitochondria in ornithine transcarbamylase-deficient spf-Mice: Restoration by acetyl-L-carnitine'. Together they form a unique fingerprint.

Cite this