Metabolism Investigation and Manipulation

By Dr Ananya Mandal, MD

Metabolic pathways are complex and often interdependent. Any change in the pathways can give rise to complex disorders. For example, imbalance of the glucose homeostasis and carbohydrate metabolism is linked to Diabetes Mellitus. This makes investigation of metabolic pathways and often manipulating them important in clinical diagnosis and management.

Investigations of metabolic pathways and disorders

One of the most helpful tools to investigate imbalanced metabolic pathways is assessment of end products of a pathway. For example, in diabetes mellitus, with lack of hormone insulin that maintains the normal blood sugar, assessment of fasting (after 8 to 10 hours of no food) and post prandial (2 hours after intake of food) blood sugar helps in diagnosis.

A valuable addition to metabolic pathway investigation is the use of radioactive tracers at the whole-organism, tissue and cellular levels, which define the paths from precursors to final products by identifying radioactively labelled intermediates and products.

Once the tagged chemicals are assessed the enzymes that catalyze these chemical reactions can be purified and their kinetics and responses to inhibitors investigated.

Another technique for detection is the identification of small molecules in a cell or tissue. These sets of molecules are called the metabolome. Overall, these studies give a good idea of the structure and function of simple metabolic pathways.

However, these studies may be inadequate when applied to more complex systems such as the metabolism of a complete cell. This is because the metabolic networks within the cell contain thousands of different enzymes and complex networks.

In fact genomes reveal that there are nearly 45000 genes that may code for enzymes and other cofactors within the metabolic pathways.

Manipulation of metabolic pathways

Since the advent of genomic studies, manipulation of gene expression from proteomic and DNA microarray studies have been developed. Many of the inborn metabolic disorders have been treated with gene therapy and manipulation of genomes coding for faulty enzymes and proteins in the metabolic pathways.

Using genetics, a model of human metabolism has now been produced, which will guide future drug discovery and biochemical research. These models are now being used in network analysis, to classify human diseases into groups that share common proteins or metabolites.

Metabolic engineering

Metabolic engineering is the targeted and purposeful alteration of metabolic pathways found in an organism. This helps in understanding and utilizing the cellular pathways for chemical transformation, energy transduction, and supramolecular assembly.

Metabolic engineering uses organisms such as yeast, plants or bacteria that are genetically modified to make them more useful in biotechnology and aid the production of drugs such as antibiotics or industrial chemicals such as 1,3-propanediol and shikimic acid. These modifications are aimed at reducing the amount of energy used to produce the product, increase yields and reduce the production of wastes.

Metabolic engineering draws principles from chemical engineering, computational sciences, biochemistry, and molecular biology.  It involves application of engineering principles of design and analysis to the metabolic pathways in order to achieve a particular goal.

Reviewed by April Cashin-Garbutt, BA Hons (Cantab)

Sources

  1. http://www.hkmj.org/article_pdfs/hkm9609p264.pdf
  2. http://www.actabp.pl/pdf/1_2008/107.pdf
  3. http://www.baybio.org/pdf/IMPACT07_Metab.pdf
  4. http://www.microbialcellfactories.com/content/pdf/1475-2859-10-91.pdf
  5. http://epc2010.org/cd/Abstracts/878.pdf
  6. http://www.scielo.cl/pdf/ejb/v1n3/a03.pdf

Further Reading

Last Updated: Oct 31, 2012

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