Models of the human metabolic network: aiming to reconcile metabolomics and genomics

摘要

The metabolic syndrome, inborn errors of metabolism, and drug-induced changes to metabolic states all bring about a seemingly bewildering array of alterations in metabolite concentrations; these often occur in tissues and cells that are distant from those containing the primary biochemical lesion. How is it possible to collect sufficient biochemical information from a patient to enable us to work backwards and pinpoint the primary lesion, and possibly treat it in this whole human metabolic network? Potential analyses have benefited from modern methods such as ultra-high-pressure liquid chromatography, mass spectrometry, nuclear magnetic resonance spectroscopy, and more. A yet greater challenge is the prediction of outcomes of possible modern therapies using drugs and genetic engineering. This exposes the notion of viewing metabolism from a completely different perspective, with focus on the enzymes, regulators, and structural elements that are encoded by genes that specify the amino acid sequences, and hence encode the various interactions, be they regulatory or catalytic. The mainstream view of metabolism is being challenged, so we discuss here the reconciling of traditionally quantitative chemocentric metabolism with the seemingly 'parameter-free' genomic description, and vice versa.