GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE ABNORMALITY IN METABOLICALLYSTRESSED HUNTINGTON DISEASE FIBROBLASTS

Huntington disease (HD) fibroblasts subjected to stress exhibit an enz yme profile that is different from that exhibited by escapee (unaffect ed members of families with HD) or control fibroblasts. The specific a ctivity of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in normall y cultured HD fibroblasts was not different from that in control and e scapee fibroblasts. However, in escapee and control fibroblasts subjec ted to stress by withholding fresh medium. the specific activity of GA PDH in cells harvested by trypsinization increased greatly 3 weeks aft er withholding medium (similar to 8-fold), but the increase was signif icantly less pronounced (similar to 3-fold) in the HD fibroblasts. In contrast, only small changes occurred in the specific activity of lipo amide dehydrogenase (LADH) over the same time period, and the values w ere not significantly different among the three groups at any time poi nt. The specific activity of hexokinase (HK) was significantly higher in the HD fibroblasts at 1-3 weeks after withholding fresh medium than in the escapee/control fibroblasts. Finally, the total yield of fibro blasts per culture flask (as judged by protein content) was significan tly greater for the stressed HD fibroblasts than for the escapee and c ontrol fibroblasts at 3 and 3 weeks after withholding medium. The pres ent results are in accord with the hypothesis that HD is a disease ass ociated with latent, generalized metabolic abnormalities.