Regulation of polyglycerophospholipid biosynthesis

Abstract

Cardiac ischaemia is a condition in which there exists an imbalance between the myocardial oxygen demand and coronary arterial supply. Biochemical complications arising from cardiac ischaemia include ATP depletion, a net loss of adenine nucleotides, as well as an increase in $\rm\lbrack Ca\sp{2+}$), (P$\sb{\rm i}\rbrack,$ and $\rm\lbrack H\sp+\rbrack.$ Ironically, cells may endure a non-lethal period of ischaemia, only to succumb to reperfusion injury. Reperfusion injury is a consequence of cell reoxygenation whereby the proliferation of oxygen free radicals (and resultant oxidative stress), increased $\rm\lbrack Ca\sp{2+}\rbrack,$ continued ATP deprivation, and higher pH all contribute to the reversible formation of a non-selective permeability transition pore in the inner mitochondrial membrane. The opening of this pore results in the further decoupling the cell's oxidative phosphorylation mechanisms, resulting in a vicious cycle of pore formation and decreased cellular metabolic efficiency. Cyclosporin A(CSA), an immunosuppressant, has been found to reverse pore formation in the post-ischaemic heart. Our goal was to study the effects of the opening and closing of these pores on cardiolipin biosynthesis. (Abstract shortened by UMI.)