Mitochondrial electron transport biological activity

Piericidins are the first compounds obtained by the screening search for insecticidal natural products among microbial metabolites.10 They were isolated from Streptomyces mobaraensis in 1963,11 and many piericidin derivatives have been found in microbial metabolites until now.12 Piericidins are not used as insecticides practically, but are important biological reagents because they have specific inhibitory activity toward the mitochondrial electron transport chain protein nicotinamide adenine dinucleotide (NADH)-ubiquinone reductase (complex I).13 Piericidin Ax (1 in Figure 1) is biosynthesized as a polyketide,14 but genes responsible for its biosynthesis are not yet identified. Total synthesis of piericidins A (1) was reported recently.15... 

The existence of membrane-bound enzymes has been known for many years and it has been proposed that most particulate enzymes are associated with the lipid matrix of biological membranes. Fleischer Klouwen (1961) were the first to show the lipid requirement in enz3nne reactions of the mitochondrial electron transport system. It is now recognized that there are a number of membrane-bound enzymes which require phospholipid for function. Any lipid-requiring enzyme must fulfill two minimal experimental criteria for proof of lipid involvement, namely (a) removal of lipid by mild procedures result in loss of enzymic activity, and (b) the activity is restored when lipids are added in a suitable physical state to the delipidized enz3mies. Point (b) entails the demonstration that activity is restored after rebinding of phospholipid to the enzyme. 

The discussion to this point has focused on the isolation of intact mitochondria. By various chemical and physical treatments, mitochondria may be separated into their four components. This allows biochemists to study the biological functions of each component. For example, by measuring enzyme activities in each fraction, one can assign the presence of a particular enzyme to a specific region of the mitochondria. Studies of mitochondrial subfractions have resulted in a distribution analysis of enzyme activities in the four locations (Table E10.1). This type of study is often referred to as an enzyme profile or enzyme activity pattern and the enzyme may be considered a marker enzyme. For example, cytochrome oxidase, which is involved in electron transport, is a marker enzyme for the inner membrane. 

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