Metabolic pathway manipulation

The World Wide Web has transformed the way in which we obtain and analyze published information on proteins. What only a few years ago would take days or weeks and require the use of expensive computer workstations can now be achieved in a few minutes or hours using personal computers, both PCs and Macintosh, connected to the internet. The Web contains hundreds of sites of Interest to molecular biologists, many of which are listed in Pedro s BioMolecular Research Tools (http // www.fmi.ch/biology/research tools.html). Many sites provide free access to databases that make it very easy to obtain information on structurally related proteins, the amino acid sequences of homologous proteins, relevant literature references, medical information and metabolic pathways. This development has opened up new opportunities for even non-specialists to view and manipulate a structure of interest or to carry out amino-acid sequence comparisons, and one can now rapidly obtain an overview of a particular area of molecular biology. We shall here describe some Web sites that are of interest from a structural point of view. Updated links to these sites can be found in the Introduction to Protein Structure Web site (http // WWW.ProteinStructure.com/). 

Although thymidine-5 -triphosphate is an almost universal component of DNA, it is exclusively derived from thymidine-5 -monophosphate (TMP). In contrast, TdR does not occur naturally and so it is impossible to manufacture TdR by manipulation of existing metabolic pathways as for most biochemical intermediates. This problem was addressed... 

There are only a limited number of chemical manipulations that a single enzyme can perform, so that for a major chemical change, more than one enzyme is required for example, to convert glucose into ethanol or laetie aeid, more than ten enzymes are required and they function as a coordinated sequence. Such a sequence is called a pathway. Since the first pathways to be elucidated were in the field of metabolism, the term metabolic pathway is a familiar term to almost all biochemists. However, the... 

Metabolic pathway analysis basic concepts and scientific applications in the post-genomic era. Biotechnol. Prog. 15, 296-303. Short, advanced discussion of theoretical treatments that attempt to find ways of manipulating metabolism to optimize the formation of metabolic products. 

Altering the control of metabolic pathways can also be achieved by genetic manipulation. As proteins are generated using the template stored as a fragment of DNA, the structure of the allosteric enzyme may be altered so that there is little or no regulatory control. It is therefore possible to generate mutants that over-produce metabolites, and techniques based on this principle have been most widely exploited in amino-acid and nucleotide production 2 . 

Plant oil metabolic pathways have also been studied to identify enzymes that may be of industrial interest in modifying or manipulating plant oils. Study of... 

The prescient remarks of Fredrickson in 1961 that investigations into Tangier disease will shed light on poorly understood lipid and fat metabolic pathways have now been borne out. An unanticipated bonus has been the identification of a molecular target for pharmacological manipulation might help lower the risk of CAD in the normal population. 

The field of pathway bioinformatics is concerned with a range of problems related to the representation and the manipulation of metabolic information within computers. How do we capture our knowledge accurately about metabolic pathways and enzymes within the computer How do we construct databases of metabolic information How do we predict the metabolic pathways of an organism from its sequenced genome, and how do we compare the metabolic networks of two organisms ... 

DHA, will be able to achieve this is, at least to the present authors, far from clear. It is not beyond the bounds of possibility that such genetically modified plants may produce much less oil than the normal plant as the energy and reducing power needed (by the desaturase and elongase reactions) to produce the PUFAs must come from the same sources that are being used to synthesize the normal fatty acids. The situation in plants may parallel what was found with the production of GLA in Mucor spp. (see Section 2.2.1) You can either find strains that produce a lot of oil but have little GLA, or you can find strains that produce a lot of GLA but have little oil, but you cannot have both occurring simultaneously. It may then take additional genetic manipulations to correct this imbalance, but distortion of one metabolic pathway can only be achieved at the expense of another so this is not likely to be a trivial task. 

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