beta - Oxidation
Lipids Metabolism

Reye's syndrome and beta-oxidation:

Drugs' role:

Recent studies have demonstrated that aspirin metabolites (salicylate, hydroxihippurate and gentisate) directly inhibit the long chain 3-hydroxyacil-Coa dehydrogenase activity and so the beta oxidation at this step LINK.
Another study has shown that toxins such as hypoglycin, pentanoate, valproate, salicylate, and their metabolites inhibit beta-oxidation pathways and can produce Reye's syndrome-like presentations LINK. Biochemical manifestations of the different causes of Reye's syndrome-like disorders are similar and include: hypoglycaemia due to impaired gluconeogenesis, accumulation of fatty acids, fatty acyl CoAs, and acyl carnitines with depletion of free CoA and carnitine. Accumulated products may further injure mitochondria and exacerbate impaired beta-oxidation, uncouple oxidative phosphorylation or increase mitochondrial permeability

Genetic deficiency's role and beta oxidation's role:

Table referred to article

The pathophysiological manifestations in patients with acyl-CoA dehydrogenation deficiencies resemble in many respect those seen in patients with Reye's syndrome, in which the fatty acid oxidation also seems to be compromised LINK. Ethiological factors have not been identified in Reye's syndrome, but in many patients blood accumulation of short- and medium-chain fatty acids has been found LINK.

In multiple acyl-CoA dehydrogenase deficiency, Reye syndrome, and Jamaican vomiting sickness octanoyl-CoA accumulate . Octanoyl-CoA inhibits complex III of the respiratory chain. Impairment of mitochondrial energy metabolism by accumulating short- and medium-chain acyl-CoAs – especially octanoyl-CoA–act synergistically with other toxic metabolites inducing a secondary severe inhibition of key enzymes of mitochondrial energy metabolism resulting in multiorgan failure or even death if untreated LINK.
It was also found that ATP concentrations also were reduced with the higher octanoate concentration. These effects of octanoate may contribute to the severe astrocyte swelling observed in the brains of Reye's syndrome patients LINK.

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