Metabolism of metals

Introduction

Metal metabolism is a crucial aspect of cellular biochemistry, encompassing the processes by which cells take up, transport, store, and expel metal ions. This course aims to provide an in-depth understanding of the various mechanisms involved in metal metabolism, with a focus on their biological significance and regulatory aspects.

Background

Metals are essential elements for all living organisms, serving as cofactors for enzymes, participating in redox reactions, and acting as structural components of proteins and nucleic acids. However, their toxicity at elevated levels necessitates stringent control over metal homeostasis to maintain optimal concentrations within cells.

Essential Metals

The essential metals can be broadly categorized into four groups: iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn). Each of these metals plays unique roles in cellular metabolism, with deficiencies leading to specific pathologies.

Iron

Iron is the most abundant transition metal in the human body and is a vital component of hemoglobin, myoglobin, cytochromes, and several other enzymes involved in oxygen transport, electron transfer, and metabolism. Iron homeostasis is regulated by iron-binding proteins such as transferrin and ferritin.

Zinc

Zinc is a key component of over 300 enzymes, including those involved in DNA synthesis, protein synthesis, and antioxidant defense. It also plays a role in immune function, cell growth, and wound healing. The transport of zinc within cells is mediated by ZnT proteins, while Zip proteins facilitate its uptake from the extracellular space.

Copper

Copper is an essential component of various enzymes involved in redox reactions, energy metabolism, and neurotransmitter synthesis. Cuproenzymes include cytochrome c oxidase, superoxide dismutase, and dopamine beta-monooxygenase. Copper homeostasis is regulated by the copper transport ATPases ATP7A and ATP7B.

Manganese

Manganese is involved in antioxidant defense, nucleic acid metabolism, and glycolysis. It serves as a cofactor for several enzymes, including arginase, glutamate dehydrogenase, and pyruvate carboxylase. Manganese homeostasis is maintained by the ATP7A and SLC30A10 transporters.

Toxic Metals

In addition to essential metals, many toxic metals are ubiquitous in the environment, posing significant risks to human health. Examples of toxic metals include lead (Pb), mercury (Hg), cadmium (Cd), and aluminum (Al).

Lead

Lead is a potent neurotoxin that affects brain development, particularly in children. It can interfere with calcium homeostasis, inhibit enzyme activity, and disrupt the blood-brain barrier. The primary route of lead exposure is through contaminated food and water.

Mercury

Mercury exists in three forms: elemental (or metallic) mercury, inorganic mercury, and organic mercury. Inorganic and organic forms of mercury are particularly toxic and can cause damage to the nervous system, kidneys, and developing fetuses. Sources of mercury exposure include contaminated seafood, dental amalgam fillings, and industrial emissions.

Cadmium

Cadmium accumulates in the kidneys and liver and can lead to kidney damage, osteoporosis, and increased susceptibility to infections. It interferes with calcium metabolism and zinc homeostasis, as well as inhibiting several enzyme activities. Cadmium is primarily found in tobacco smoke, industrial emissions, and certain foods such as shellfish and liver.

Aluminum

Aluminum is not considered an essential metal, but it is ubiquitous in the environment and can accumulate in the brain, particularly in individuals with kidney disease or genetic disorders affecting aluminum transport. Chronic exposure to aluminum has been associated with neurological symptoms such as dementia and Alzheimer's disease.

Metal Detoxification Mechanisms

Cells possess several mechanisms for detoxifying excess metal ions, including:

• chelation by metallothioneins
• sequestration in intracellular storage compartments (e.g., lysosomes)
• excretion via bile or urine

Conclusion

Understanding the metabolism of metals is vital for understanding cellular biochemistry and maintaining human health. This course has provided an overview of the essential and toxic metals, their roles in cellular metabolism, and the mechanisms by which cells maintain metal homeostasis. Further study in this area may lead to the development of novel strategies for preventing and treating metal-related diseases.