Oxidative pathway delay

Skaper, S. D., Facci, L, Romanello, S., and Leon, A. (1996). Mast cell activation causes delayed neurodegeneration in mixed hippocampal cultures via the nitric oxide pathway. J. Neurochem. 66, 1157-1166. 

In general, phase I reactions, such as oxidation and ra-demethylation are delayed in the neonate but are fully operational at or above adult levels by 4-6 months of age in the full-term neonate [27a-30]. Conjugation pathways, such as glucuronidation, do not approach adult values until 3 or 4 years of age. Sulfation activity does appear to reach adult levels in early infancy. For drugs that are subject to metabolism by both pathways, such as acetaminophen, the efficient activity of the sulfation pathway allows infants and children to compensate for low glucuronidation ability... 

Pyruvate carboxylase deficiency is one of the genetic diseases grouped together under the clinical manifestations of Leigh s disease (subacute necrotizing encephalopathy). In the mild form, the patient presents early in life with delayed development and a mild-to-moderate lactic acidemia. Patients who survive are severely mentally retarded, and there is a loss of cerebral neurons. In the brain, pyruvate carboxylase is present in the astrocytes, which use TCA cycle intermediates to synthesize glutamine. This pathway is essential for neuronal survival. The major cause of the lactic acidemia is that cells dependent on pyruvate carboxylase for an anaplerotic supply of oxaloacetate cannot oxidize pyruvate in the TCA cycle (because of low oxaloacetate levels), and the liver cannot convert pyruvate to glucose (because the pyruvate carboxylase reaction is required for this pathway to occur), so the excess pyruvate is converted to lactate. 

A mechanism for the pathophysiology of high-flow priapism is described by Bastuba et al. (1994). Unlike a traditional arteriovenous fistula, the condition is described as an arterial-lacunar fistula where the helicine arteries are bypassed, and the blood passes directly into the lacunar spaces. The high-flow in the lacunar space creates shear stress in adjacent areas, leading to increased nitric oxide release, activation of the cGMP pathway, smooth muscle relaxation and trabecular dilatation. These authors also postulate that the delay in onset of high-flow priapism may be secondary to a delay in the complete necrosis of the arterial wall after the initial trauma or secondary to clot formation at the site of injury followed by the normal lytic pathway, which progresses in a few days. 

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