6-aminonicotinamide (6-AN), an analogue and antagonist of nicotinamide, impairs cartilage formation and results in shortening of the limb when administered to chick embryos. 6-AN forms an abnormal NAD analogue (6-ANAD), which inhibits the activity of NAD-dependent enzymes associated with the production of ATP. The mechanism of action of 6-AN was studied by measuring the biosynthesis of protein and DNA, and the sulfation and glycosylation of chondroitin sulfate in control and 6-AN treated cartilage from 8-day chick embryos. The cartilage was also assayed for ATP levels. Incorporation of Na235SO4 was inhibited by 6 h treatment with 10 μg/ml 6-AN, whereas 3H-thymidine and 3H-amino acid incorporation were not inhibited until 12 h. 3H-glucosamine incorporation was not inhibited during any of the treatment times examined. Decrease in the level of ATP preceded inhibition of Na235SO4 incorporation. These results are consistent with the view that 6-AN inhibits chondroitin sulfate synthesis through a reduction in the level of ATP in chondrocytes.
College and Department
Life Sciences; Plant and Wildlife Sciences
BYU ScholarsArchive Citation
Sheffield, Val C., "The relationship of reduced levels of ATP to inhibited chondrogenesis in the production of limb deformity induced by 6-aminonicotinamide" (1977). Theses and Dissertations. 7870.
Nicotine; Abnormalities, Human