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Biochemical Genetics

, Volume 25, Issue 1–2, pp 7–25 | Cite as

The effects of recessive lethal Notch mutations of Drosophila melanogaster on flavoprotein enzyme activities whose inhibitions cause Notch-like phenocopies

  • George E. W. Thörig
  • Pieter W. H. Heinstra
  • Barbara L. A. de Ruiter
  • Willem Scharloo
Article

Abstract

The biochemical action of the Notch locus whose mutants cause morphological aberrations in flies, viz., notches of wings and bristle multiplication, has been analyzed (1) by the addition to the food medium of enzyme inhibitors causing phenocopies of Notch and (2) by comparison of enzyme activity patterns of Notch mutants with different degrees of phenotypic expression. Notch phenocopies were induced by inhibitors of enzyme activities in two biochemical pathways: (1) the de novo pyrimidine synthesis by 5-methylorotate (inhibitor of dihydroorotate dehydrogenase) and (2) the choline shunt by amobarbital (inhibits choline dehydrogenase) and methoxyacetate (inhibits sarcosine dehydrogenase). The inhibition of de novo pyrimidine synthesis prevents the production of deoxyuridine-5-phosphate, the substrate for the synthesis of thymidine-5-phosphate via thymidylate synthase, whereas the inhibition of the choline shunt prevents the production of HCHO groups and glycine, both of which are involved in the synthesis of 5,10-methylenetetrahydrofolate, which is a cofactor of thymidylate synthase. It was already known that the inhibition of the latter enzyme in vivo induces Notch phenocopies. Notch mutants with a strong morphological expression show low enzyme activities for dihydroorotate dehydrogenase and choline dehydrogenase. Both are flavoprotein enzymes linked to the respiratory chain. The correspondence between the low enzyme activities in Notch mutants with a strong morphological expression and the phenocopying effect of antimetabolites on these enzymes in the two biochemical pathways involved strongly suggests that the morphological effects of Notch on flies are a consequence of lowered activities of choline dehydrogenase and dihydroorotate dehydrogenase.

Key words

Drosophila melanogaster Notch locus wing morphology phenocopies choline dehydrogenase dihydroorotate dehydrogenase xanthine dehydrogenase (O2sarcosine dehydrogenase 

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Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • George E. W. Thörig
    • 1
  • Pieter W. H. Heinstra
    • 1
  • Barbara L. A. de Ruiter
    • 1
  • Willem Scharloo
    • 1
  1. 1.Department of Population and Evolutionary BiologyRijksuniversiteit UtrechtUtrechtThe Netherlands

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