Journal article
Impaired energy metabolism as an initial step in the mechanism for 6-aminonicotinamide-induced limb malformation
Journal of embryology and experimental morphology, Vol.59(1), pp.217-222
10/1980
PMID: 6452487
Abstract
The analogue and antagonist of nicotinamide, 6-aminonicotinamide (6-AN), impairs cartilage formation and results in shortening of the limbs when administered to chick embryos. Studies have shown that 6-AN forms an abnormal NAD analogue which inhibits the activity of NAD-dependent enzymes associated with production of ATP. To determine if an effect on ATP synthesis might be associated with the mechanism of teratogenesis in the chick embryo, ATP levels of cartilage from day-8 chick embryos treated in vitro were assayed in relation to biosynthesis of protein, DNA and chondroitin sulfate. Incorporation of 35SO4= was inhibited by 6 h or treatment with 10 microgram/ml of 6-AN, whereas incorporation of [3h]thymidine and [3H]amino acid was not inhibited until 12 h. Incorporation of [3H]glucosamine was increased at all treatment times. A decrease in the level of ATP preceded any detectable inhibition of precursor incorporation. These results are consistent with the hypothesis that 6-AN inhibits chondroitin sulfate synthesis through a reduction in the level of ATP in chondrocytes.
Details
- Title: Subtitle
- Impaired energy metabolism as an initial step in the mechanism for 6-aminonicotinamide-induced limb malformation
- Creators
- V C SheffieldR E Seegmiller
- Resource Type
- Journal article
- Publication Details
- Journal of embryology and experimental morphology, Vol.59(1), pp.217-222
- Publisher
- England
- PMID
- 6452487
- ISSN
- 0022-0752
- eISSN
- 1477-9129
- Language
- English
- Date published
- 10/1980
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065398702771
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