Sec_8 - Regulation 8-1 Several aspects of regulation have...

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8-1 R e g u l a t i o n Several aspects of regulation have been alluded to or described in detail as we have progressed through the various sections of the course. These include: (a) compartmentation : This was not described overtly as a control mechanism, but is implicit in the situation of E -oxidation of fatty acids (degradation) occuring inside the mitochondria and synthesis occuring in the cytoplasm. In this way, if one pathway is turned on, there is no competition from the other pathway operating in the opposite direction. (b) hormonal : The effect of hormones was mentioned in a few sections, but the main contact was in glycogen metabolism where adrenalin was shown to activate protein kinase in the complex process affecting glycogen synthesis and degradation. (c) feedback inhibition and activation : There were many examples of this ranging from energy metabolism to pyrimidine synthesis. This is often referred to as short term control , because the inhibition or activation can occur as fast as an effector molecule can bind to a protein. (d) protein modification : This is best illustrated by the role of protein kinase and protein phosphatase in glycogen metabolism. This is also an example of post-translational control Other types of control occur at the level of RNA and protein synthesis ( transcriptional and translational controls). Of these, transcriptional control has been found to be more common. These are often referred to as long term control because the response time is longer requiring either the synthesis or degradation of a protein. (e) control of RNA levels : As noted this control occurs at the level of either transcription or translation and is referred to as long term control. 1. S h o r t t e r m c o n t r o l A B C D E feedback inhibition by an end product of the pathway In a linear pathway, the end product E acts at an early step, shutting down the whole pathway and saving energy. aspartate + carbamoyl phosphate N-carbamoyl apartate aspartate transcarbamoylase Pi CTP
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8-2 Whereas control of a linear pathway is relatively straightforward, control of a branched pathway presents more of a challenge because of the existence of multiple end products (E and G below). A system is needed to allow both end products a role in regulating overall expression of the pathway and a number of systems have evolved that make this possible. D E A B C F G (a) multiple enzyme control : Multiple alleles of the same enzyme exist to catalyze a step early in the pathway that are affected differently by different inhibitors. This controls the overall pathway but additional sites of control are required in each branch after the branch point. D E A B C F G I II (b) sequential feedback : The end products inhibit a step after the branch which cause a build up of an intermediate which acts sequentially to inhibit a step early in the pathway.
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This note was uploaded on 02/27/2011 for the course MBIO 2370 taught by Professor Spearman during the Winter '11 term at Manitoba.

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Sec_8 - Regulation 8-1 Several aspects of regulation have...

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