Eskouhie Tchaparian

Biochemistry: is pyrroloquinoline quinone a vitamin?

Arising from: T. Kasahara & T. Kato 422, 832 (2003); see also communication from Felton and Anthony; Kasahara et al. reply The announcement by Kasahara and Kato of pyrroloquinoline quinone (PQQ) as a ‘new’ vitamin has received considerable attention. We have since attempted to reproduce the findings on which their conclusion is based, namely that defects in lysine metabolism occur in PQQ-deprived rodents. However, we find that the activity of α-aminoadipic acid-δ-semialdehyde (AAS) dehydrogenase in liver and plasma levels of α-aminoadipic acid (AAA), both of which act as indicators of lysine degradation in mammals, are not affected by changes in PQQ dietary status. Our results call into question the identification of PQQ as a new vitamin.

Dietary Copper, Vanadate, Lysyl Oxidase Activity, and Lysine Tyrosyl Quinone Formation

Lysyl oxidase activity is critical for the assembly and crosslinking of extracellular matrix proteins, such as collagen and elastin. Lysyl oxidase can also serve as a vehicle for copper transport from extracellular matrix cells. Lysyl oxidase activity is sensitive to changes in dietary copper status and is influenced by metabolic and genetic perturbations in copper transport, specifically, mutations in the copper-transporting ATPase gene, PATPase-7A. Herein, the effects of nutritional copper deprivation, sodium vanadate toxicity, and Menkes’ disease are described with respect to copper accumulation in connective tissue cells and lysyl oxidase activation. A principle goal was to characterize features of lysyl oxidase activation. Dietary copper deficiency, sodium vanadate treatment, and observations using Menkes’ cells in culture are compared. Dietary copper deficiency causes a decrease in lysyl oxidase activity, but not in the amount of expressed lysyl oxidase protein (Rucker et al., 1996). Feeding sodium vanadate caused increased accumulation of copper in cells, but decreased accumulation of activated lysyl oxidase. The Menkes’ phenotype is also characterized by increased copper accumulation and decreased expression of active lysyloxidase (Kosonen et al., 1997). One explanation is that copper deficiency affects the post-translational formation of the active-site quinone cofactor of lysyl oxidase, lysine tyrosyl quinone (Wang et al., 1997).