Metallobiochemistry, the study of the biochemistry of metallic compounds, is a broad discipline that draws together the expertise of biochemists, analytical chemists, and clinical chemists. The field encompasses the study of metalloenzymes, the development of new analytical methods for investigating metals, and the application of new techniques to biological and clinical problems.
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Here, we explore the various applications of metallobiochemistry and define its importance in modern science.
The study of metalloenzymes
Metalloenzymes are enzymes that contain metal cofactors (metal ions) that are bound directly to the protein, or prosthetic groups (enzyme-bound non-protein components). Studies have revealed that anything from one third to a half of all known enzymes are classed as metalloenzymes, making them a key area of study.
In addition to metalloenzymes, other metalloproteins exist that play a part in non-enzyme electron transfer reactions, act as storage (in the case of ferritin for iron), or, transport proteins (in the case of transferrin for iron). Additionally, ribozymes (molecules of RNA with enzyme function) may contain metal ions that are functionally and/or structurally significant and, therefore, may also be classed as metalloenzymes.
The study of these enzymes is vital for gaining a deeper understanding of many aspects of human and animal physiology, such as catabolism, mitochondrial function, transcriptional regulation, and brain function. Research is mounting to support the theory that metalloenzymes play an important role in the establishment and development of neurodegenerative disease and other illnesses.
Therefore, metallobiochemistry will be essential to the development of preventative, treatment, and diagnostic methods for disease. The study of metalloenzymes will likely be increasingly relied on to help gain a deeper understanding of the pathophysiology of disease.
Measuring metal pollutants in the body
A large body of evidence exists that demonstrates the significant negative impact that long-term exposure to heavy metals has on the body. It can cause muscular, physical, and neurological degeneration. In particular, long-term exposure to heavy metals has been linked with Alzheimer's disease, multiple sclerosis, muscular dystrophy, and Parkinson's disease.
For this reason, monitoring human exposure to heavy metals has become increasingly important as our knowledge grows of the danger it poses to long-term health. One major source of heavy metal exposure is environmental pollution. Scientists have been working on developing ways to monitor how metal pollutants impact biochemical functions, and well as investigating how to accurately monitor levels of metals in the environment.
Metallobiochemistry offers a vital platform for the study of heavy metals in the environment and their impact on biological systems. Currently, techniques of metallobiochemistry are being used to study how metal pollutants accumulate within the human body over time, as well as to identify metal biocomplexes. Because heavy metal pollution exists at relatively low levels in the environment, incredibly sensitive analytical techniques are called upon to assess them and their effects.
Metallobiochemistry is now incorporating nuclear and radiochemical techniques, including Cerenkov counting, high-resolution γ-ray spectrometry, multiple tracing, and neutron activation analysis, alongside biochemical methods such as differential centrifugation, ion-exchange chromatography, gel filtration, and polyacrylamide gel electrophoresis, to accurately study heavy metals in this context.
Therapeutic intervention
As discussed, metallobiochemistry plays a key role in the study of substances that are related to diseases, such as metalloenzymes and heavy metals. Unsurprisingly, the field of metallobiochemistry has become important in the development of therapeutic interventions for various diseases.
Importantly, metalloenzymes present valuable medicinal targets. They play vital roles in numerous metabolic pathways and are implicated in a variety of physiological functions. Research has shown that they are often over-expressed in a wide range of diseases, such as Alzheimer's disease, kidney fibrosis, polycystic kidney disease, Huntington's disease, cancer heart disease, and more.
Because of their key role in many diseases, metalloenzymes have already been well-exploited as medicinal targets with the help of metallobiochemistry. Currently, this area of research is still incredibly active, with many studies underway that continue to explore how metalloenzymes can be further exploited for therapeutic interventions.
The future of metallobiochemistry
Metallobiochemistry has already been proven to be vital for numerous applications including the study of metalloenzymes, monitoring of environmental pollution, and development of new therapeutic interventions. Metallobiochemistry will likely continue to be relevant in these applications, particularly in the development of new medicines, given the vast number of diseases that metalloenzymes are implicated in.
As biochemists, analytical chemists, and clinical chemists continue to combine their expertise within the field of metallobiochemistry, we can expect the development of new analytical methods to continue to emerge, and with it, new ways to apply these methods to biological problems, such as disease management and treatment.
While the discipline of metallobiochemistry is not new, it is still evolving and growing its applications, particularly in medical science.
Sources:
- Analytical Chemistry, 1989. Metallobiochemistry. 61(4), pp.308A-309A. https://pubs.acs.org/doi/pdf/10.1021/ac00179a731
- Chen, A., Adamek, R., Dick, B., Credille, C., Morrison, C., and Cohen, S., 2018. Targeting Metalloenzymes for Therapeutic Intervention. Chemical Reviews, 119(2), pp.1323-1455. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405328/
- Girardi, F., Marafante, E., Pietra, R., Sabbioni, E., and Marchesini, A., 1977. Application of neutron activation analysis to metallobiochemistry. Journal of Radioanalytical Chemistry, 37(1), pp.427-440. https://link.springer.com/article/10.1007/BF02520549
- Hoppert, M., 2011. Metalloenzymes. Encyclopedia of Geobiology, pp.558-563. link.springer.com/referenceworkentry/10.1007%2F978-1-4020-9212-1_134
- Lothian, A., Hare, D., Grimm, R., Ryan, T., Masters, C., and Roberts, B., 2013. Metalloproteomics: principles, challenges, and applications to neurodegeneration. Frontiers in Aging Neuroscience, 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714543/
- Sabbioni, E., and Girardi, F., 1977. Metallobiochemistry of heavy metal pollution: Nuclear and radiochemical techniques for long term-low level exposure (LLE) experiments. Science of The Total Environment, 7(2), pp.145-179. https://www.sciencedirect.com/science/article/abs/pii/0048969777900055
Further Reading