Red blood cells from 18 lithium carbonate-treated patients with bipolar affective disorder and 12 normal volunteers were analyzed using 1H-nuclear magnetic resonance (NMR) spectroscopy. The spectra were analyzed for alanine, adenosine triphosphate (ATP), choline, 2,3-diphosphoglycerol, glucose, glutathione, glycine, and lactate. Significant elevations of choline and lactate were found in the lithium-treated patients compared with normal, unmedicated subjects. The elevation of lactate due to anaerobic metabolism in the red blood cells was further investigated via fluorometric analysis and appears to be caused by blood standing at room temperature. The observed increases in red blood cell choline are sufficiently high and statistically significant to warrant additional studies on the dramatic effects of lithium on this red cell metabolite, which might be important for an understanding of its mechanism of action in psychiatric disorders.
The enzyme xanthine: acceptor oxidoreductase found in rat heart equilibrates between three forms differing in electron acceptor specificity. Form D transfers electrons exclusively to NAD+ and accounts for 85% of total oxidoreductase activity. Form O transfers electrons to molecular oxygen and accounts for 8%. The D/O form prefers NAD+, but without NAD+ transfers electrons to oxygen. Interconversion from D to O and O to D forms is catalyzed by sulfhydryl group-modifying reagents: Cd2+, Cu2+, disulfiram, and heating with dithiothreitol. This suggests that sulfhydryl groups participate in the first stage of enzyme conversion. The NADH/NAD+ concentration ratio may regulate the dehydrogenase activity of xanthine:acceptor oxidoreductase (NAD+-dependent activity of D and D/O forms). Accumulating NADH inhibits hypoxanthine hydroxylation. The amount of form O increases during cardiac ischemia, facilitating superoxide radical-ion generation. Also, NADH/NAD+ does not regulate form O, promoting adenylate nucleotide pool depletion, especially in the heart which has low de novo purine nucleotide synthesis.
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