Genetics and regulation of enzyme synthesis

Synthesis of NAD-GDH is repressed and that of NADP-GDH is induced by increasing concentrations of sucrose or glucose in the medium (173). Citrate, pyruvate, and succinate do not exert a significant effect on NAD-GDH although pyruvate and citrate do induce NADP-GDH. Additional studies have indicated that the regulation of the two GDH s is controlled by some balance between the internal amino acids and glucose metabolites (174). 

The decrease in the NADP-GDH activity with exogenous supplements like urea reflects repression of gene action rather than enzyme inhibition (166,169). The am designation is used for the locus specifying NADP-GDH, and the synthesis of the corresponding inactive proteins (CRM) by am (amination-deficient) mutants can be regulated by urea in the 

Nineteen mutations at the am locus in N. crassa have been described 175,178,179) and are specified by numerical superscripts forming the series am - to am. Some of the properties of these mutant strains are given in Table VI. Crosses between different am mutants produce low frequencies of wild-type progeny 180,181) as expected from mutations at different sites within the same gene. The present status of the linear map of the am gene is shown in Fig. 3 182,183). There is no obvious 

Various Properties Associated with Neurospora Mutant Strains 

Map of mutant sites based on frequencies of am recombinants in N. crassa. Amino acid replacements of am (residue 141) and am7 (residue 142) cannot be aligned by recombination frequency (see text). 

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Possible functions of secondary products in the metabolism of the producing organisms were discussed in a number of papers. Several different experimental approaches were developed to study a possible role of antibiotics and other secondary products in the producing cells. These include the genetic and biochemical analysis of mutants blocked in the synthesis of secondary metabolites, and the study of metabolic pathways and regulation of the synthesis and activity of enzymes involved in the production of secondary metabolites. 

Let us first discuss modern concepts about the genetic regulatory systems of bacteria and phage. The basic ideas were proposed by Jacob and Monod (Jacob and Monod, 1961 Jacob and Wollman, 1962 for review see Benzer, 1963 Kumar et al., 1970 Szybalski, 1972 Ratner, 1975 Flint, 1977 Smith, 1977 Nover et al., 1978). It was demonstrated that in bacteria there are blocks of contiguous structural genes which code for specific proteins and which are assembled into functional units or operons. These units participate for instance in the regulation of the synthesis of enzymes which in turn participate in lactose utilization (Fig. 94). 

Enzyme synthesis in vitro supplements genetic analyses by providing information on the map positions of promotors and genes. And above all, the coupled transcription-translation systems have opened new approaches into the regulation of protein synthesis such as the understanding of the control of the lactose operon and of catabolite repression. Enzyme synthesis in vitro... 

Since nicotine has wide ranging effects on the central nervous system it seems likely that pharmacogenomic effects on the development of nicotine dependence will span several neurotransmitter systems. One study found an association between a polymorphism in dopamine /1-hydroxylase and level of tobacco consumption [20]. This enzyme is important in noradrenaline synthesis and it is tempting to speculate that genetically regulated variations in activity might influence susceptibility to nicotine withdrawal symptoms mediated by noradrenergic pathways, but more information is required on the molecular effects of the polymorphism. 

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