Chunk #23 — Epigenetics-Relevant Consequences of Oxidative Alcohol Metabolism — Increases in NADH/NAD+ Ratio and Their Consequences — Modulation of Gene Expression
CtBP is a regulatory factor mediating transcriptional repression that is important for cell cycle regulation and development; it acts as a NAD+-dependent D2-hydroxyacid dehydrogenase (Kumar 2002). Studies on mice carrying altered Ctbp genes suggest that two mutant genes (Ctbp1 and Ctbp2) play unique regulatory roles during development (Chinnadurai 2003). Mice lacking a functional Ctbp1 gene (i.e., Ctbp1-null mice) are about 30 percent smaller than wild type mice, whereas Ctbp2-null mice exhibit defects in heart morphogenesis and neural structures. NAD+ enhances the interaction of CtBP with target transcription factors (Zhang et al. 2002). Furthermore, CtBP is a metabolic sensor that has been implicated in regulating adipogenesis (Jack et al. 2011). The role of CtBP and changes in the redox state caused by alcohol metabolism in ethanol-induced teratogenesis and effects on adipose tissue remains to be elucidated.
