28_Gene_Control-1

28_Gene_Control-1 - XXVIII. Gene Controll XXVIII. Gene...

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X X X X X X V V V I I I I I I I I I . . . G G G e e e n n n e e e C C C o o o n n n t t t r r r o o o l l l H o w t c n r l m e a b i s ? Inhibition or activation of enzymes results in minor adjustments of metabolic pathways. Major changes occur when the whole pathways are shut down. A good way of controlling whole pathways is the expression of participating enzymes. There are many opportunities to control gene expression: for a gene to be expressed into a functional enzyme many complicated steps have to occur each of which can be regulated: (a) DNA has to be unpacked; (b) DNA is transcribed into RNA, introns are spliced out; (d) mRNA transported out of the nucleus; (e) mRNA translated into polypeptide chains; (d) nascent protein is postranslationally modified T T T r r r a a a n n n s s s c c c r r r i i i p p p t t t i i i o o o n n n a a a l l l c c c o o o n n n t t t r r r o o o l l l : : : p p p r r r o o o k k k a a a r r r y y y o o o t t t e e e s s s For a simple pathway sketched below, one can imagine two ways of controlling the pathway: (i) appearance of initial substrate A could induce expression of the first enzyme, x, or (ii) production of the final product, G, could repress the expression of enzyme x. x y z A B C... G ↓↓ turns on expression of x inducible genes turns-off expression of x repressible genes Operon Operon Promoter Operator Genes RNA polymerase Polypeptides A B C C B A
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N e g a t i v C o n r l : R p s d A good way of modulating gene expression is at the transcriptional level. Inhibition of transcription stops expression of the enzyme dead, before it even starts. The simplest form of transcriptional control is interference with the promoter. Block the path of the polymerase by binding a protein to the DNA between the promoter and the initiation codon, and the polymerase will not be able to reach the gene. These blocking proteins are called repressors, and the site of their binding is referred to as the operator. Repressor binding to the operator can be controlled by substrate A or product G by means of allosteric interactions or competitive binding. Thus we have a switch that turns gene transcription on or off as required by the pathway above. Promoter Genes Genes not expressed Inactive repressor: no corepressor present Corepressor Active repressor: corepressor bound Genes expressed Operator I u c b These are the genes of the first kind in our scheme, appearance of the substrate for the pathway induces the expression of the gene coding for the enzyme. E. coli normally lives on glucose in our guts, but when the glucose level decreases, lactose is used as a source of glucose. To hydrolyze lactose (galactose-glucose) one needs a hydrolyzing enzyme, &- galactosidase. In the presence of glucose, the gene for &-galactosidase is permanently turned off, so we must have a means of turning it on.
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28_Gene_Control-1 - XXVIII. Gene Controll XXVIII. Gene...

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