Developmental Ontogeny of NAD+ Kinase in the Rat Conceptus

Abstract

The ubiquitous NAD+ kinase (NADK) is the only known enzyme to catalyze formation of NADP+ from NAD+. The capacity to maintain an adequate supply of NADP(H) has important implications for development because of its requirement as a cofactor and electron donor in biosynthesis and detoxication reactions. Modulation of NADK may directly influence NADP(H) concentrations and cell sensitivity to embryotoxicants. Measurable activities of NADK were not detected in gestational day (GD) 10 rat conceptuses. By GD 11, specific activities of 1.8 and 7.0 pmol NADP+/min/μg protein were measured in embryos and visceral yolk sacs (VYSs), respectively. The VYS specific activities decreased thereafter to 0.5 pmol NADP+/min/μg protein by GD 18. Specific activities of NADK in placenta increased from 1.3 pmol NADP+/min/μg protein on GD 11 to 32.7 pmol NADP+/min/μg protein on GD 15. Specific activities in the liver increased from 1.7 pmol NADP+/min/μg protein on GD 15 to 51.1 pmol NADP+/min/μg protein on GD 21. NADK specific activities were also determined in other developmentally relevant tissues such as the heart and the brain. In the heart, NADK activity was at its lowest just before birth while in the brain it peaked at 5.4 pmol NADP+/min/μg protein just prior to birth. In the lung, activity increased from 0.9 pmol NADP+/min/μg protein on GD 17 to 5.9 pmol NADP+/min/μg protein on GD 21. However, activities dropped in the kidney from 2.0 pmol NADP+/min/μg protein on GD 17 to 1.1 pmol NADP+/min/μg protein on GD 21. These results demonstrate dramatic temporal and spatial variations in NADK activity. Tissue variations in NADK activities may reflect alterations in functional needs for cofactors during differentiation and a cooperation between tissues to optimize detoxification capacity. This is particularly important when chemical exposure during pregnancy disrupts pyridine nucleotide redox status and the conceptus must rely on NADK to provide additional NADP(H).