# Structural Biochemistry/Transition Metals

Transition metals are the elements in groups 3-12 in the d-block of the periodic table. They are known to have 2 or more oxidation states.

## General Properties

The general properties of transition elements include:
* High melting points
* Several oxidation states
* Colored compounds
Other properties include high boiling points, high electrical conductivity, and malleability. The transition metals also have d-orbitals which are loosely bound. The first row transition metals generally form high spin complexes. The second and third row transition metals generally form low spin complexes. Transition metals are also able to absorb light. Red light is absorbed at low energy levels while violet light is absorbed at higher energy levels.

## Iron

Iron is a biologically important transition metal as it is also vital to life - it is one of the few trace elements needed for organisms to sustain life. It has three main biological roles: 1. Transport oxygen from lungs to cells It is used to bind to enzymes throughout the body, such as in Hemoglobin to transport oxygen throughout the human body in blood. 2. Energy Production Iron is used in the conversation of sugar, fats, and proteins into adenosine triphosphate, ATP. 3. Catalase Production Iron is involved with the production of catalase and this is important because catalase protects the body from free radical damage.
Rich sources of iron in food include: red meat, soybean, white flour products, seafood, and sunflower seeds Despite its uses in biological systems, an excess amount of iron can be detrimental to the human body. First, iron can cause enzyme dysfunctions by replacing other vital minerals. All these essential minerals compete for binding sites in enzymes, and when iron replaces the competing mineral, it causes the enzyme to malfunction. Second, when iron replaces other elements in the body, it also causes inflammation. Iron attracts oxygen and when in excess, the free radical oxygen damages the surrounding body tissue. In addition, as a carrier for oxygen, iron promotes bacterial growth by feeding it oxygen, leading to chronic infections. Iron can mostly be found in the pancreas, joints, liver, and intestines.

##### Physical Illnesses Associated with Iron

* Diabetes
* Nervous System Diseases: Parkinson’s disease, Alzheimer’s disease and behavioral abnormalities, including violence, anti-social behavior, ADHD, and autistic characteristics.
* Hypertension and Cardiac Conditions
* Kidney Problems

## Copper

Copper has a diverse role in the human body.

##### Connective Tissue and Bones

Copper repairs the calcium in bones and connective tissue. Insufficiency or excess can lead to conditions like osteoporosis, bone spurs, and scoliosis.

##### Immune System

In the immune system, copper must be in balanced with zinc. When these two elements are not balanced, the body is prone to infection, particularly yeast and fungal infections. Since copper is a critical element in aerobic metabolism, an improper level of copper allows the fungal organisms to flourish.

##### Reproductive System

Copper also plays a role in the reproductive system as it is required for pregnancy and fertility. An imbalance of copper can lead to premenstrual syndrome, ovarian cysts, miscarriages, and sexual dysfunctions. Studies have shown that woman with deficient estrogen and copper have a higher risk of miscarriage. Correcting the copper level by eating more meats, eggs, poultry, nuts, seeds, and grains can help with a normal pregnancy.

##### Nervous System

In the nervous system, copper plays a role in triggering the production of neurotransmitters epinephrine, norepinephrine and dopamine. As a result, copper imbalance can be associated with psychological, neurological, and emotional problems in humans.
Copper is used to bind to enzymes throughout the body. It is used to defend the body against damage from free radicals. Foods that contain copper include shellfish (i.e. crab, lobster, etc.), dried beans, and nuts.
Hemocyanin is an excellent example of the use in proteins. Hemocyanin is an alternative O$_2$ transport protein that involves the binding of O$_2$ to the two Cu$^{2+}$, which is then oxidized to Cu$^{3+}$ after binding. It is different from Hemoglobin in that in doesn't "tag along" with red blood cells, but is contained in hemolymph.

## Zinc

Zinc is an inorganic compound that play an active role in biological settings. Its ability to adapt to various coordination geometries and its properties as a Lewis acid and redox inert makes it an important compound in structural and catalytic biochemistry.
Zinc undergoes rapid ligand exchange and is regulated by several proteins in cell signaling. For example, in the central nervous system, zinc is released from the synaptic vesicles at some glutamatergic nerve terminals to trigger signaling pathways which affect physiological functions such as synaptic plasticity, potentiation, and cell death. In addition, diabetes studies have shown that zinc is released along with insulin to control glucose levels.
Besides from being regulated, zinc is also capable of regulating other proteins by shifting its concentration. Zinc can influence the productivity of nitric oxide which changes the immune system. Lack of zinc in the body weakens the immune system and leaves the body prone for infections. In the prostate glandular epithelium, a change in the normal concentration level can lead to complications in the prostate. In the nervous system, a concentration of zinc that is too high can mean mitochondrial dysfunctions.
Biochemistry of Mobile Zinc and Nitric Oxide Revealed by Fluorescent Sensors Michael D. Pluth, Elisa Tomat, and Stephen J. Lippard Annual Review of Biochemistry, Vol. 80: 333 -355 (Volume publication date July 2011)

## Cobalt

Cobalt is at the core of B$_{12}$ vitamins.The structure of this is based on the corrin ring. It is used to treat anemia because it stimulates the production of erythropoietin which makes red blood cells. Like any other element, a high concentration of cobalt is harmful to the human body. Excess intake of cobalt can result in vomiting, nausea, vision problems, heart problems, and thyroid damage. We mainly obtain it from the environment by breathing air, drinking water, and eating food that contain cobalt such as meats, dairy, and leafy green vegetables.
Radioactive cobalt can also cause health concerns. This type of radiation is sometimes used to treat cancer patients. Exposure affects include hair loss, diarrhea, and vomiting.
There are several enzymes that contain cobalt and use it as a ligand to bind to methyls and adenosyl. It is thought that cobalt acts by inhibition of enzymes involved in oxidative metabolism and that the response is the result of tissue hypoxia. More specifically, cobalt blocks the conversion of pyruvate to acetyl coenzyme A (coA) and of α-ketoglutarate to succinate.

## Mercury

Mercury was an important constituent of drugs for centuries-as an ingredient in many diuretics, antibacterials, antiseptics, skin ointments, and laxatives. The use of mercury in medicinal preparations has dramatically decreased due to the toxic effects that it has in the human body, such as nausea, vomiting, abdominal pain, bloody diarrhea, kidney damage, and death. Mercury readily forms covalent bonds with sulfur, and it is this property that accounts for most of the biological properties of the metal. When the sulfur is in the form of sulfhydryl groups, divalent mercury replaces the hydrogen atom to form mercaptides, X-Hg-SR and Hg(SR)2, where X is an electronegative radical and R is a protein. Organic mercurials form mercaptides of the type RHg-SR'. Mercurials even in low concentrations are capable of inactivating sulfhydryl enzymes and thus interfering with cellular metabolism and function. Mercury also combines with other ligands of physiological importance, such as phosphoryl, carboxyl, amide, and amine groups[1].

## Chromium

In mammals, chromium, a micronutrient, is only required in small quantities in biological systems. While the exact roles that chromium plays in the body is still unknown, research has proposed that chromium helps maintain proper carbohydrate and lipid metabolism. In the late 1950s. Schwarz and Mertz showed the importance of chromium through experiments involving the diets of rats. When the rats were fed with Torula yeast, a diet lacking chromium, the rats were unable to efficiently remove glucose from the bloodstream. Then when the rats were fed with food rich in chromium, the rats were able to maintain a normal glucose level. This experiment became evidence that chromium depends on insulin.
In the 1980s, Wada and Yamamoto were able to isolate the oligopeptide that binds chromium. This peptide is called chromodulin. Chromodulin is a small molecule of about 1500 Da and can bind four equivalents of chromium ions. The most significant characteristic of chromodulin is its ability of effect insulin by conversion of glucose into carbon dioxide or lipid.
In addition, there has also been some studies that suggests chromium and chromodulin play a role in signal transduction. Analysis of how chromodulin activate or inhibit phosphatase and kinase activity in rat adipocytes reveal an effect of small activation of a membrane phosphotyrosin phosphatase and a significant stimulation of insulin receptor tyrosine kinase activity.

## Manganese

The human body averagely contains about 10 to 20 milligrams of manganese mostly concentrated in the pancreas, bone, liver, and kidneys. Manganese plays a role as a cofactor to important enzymes in the mitochondria and in the synthesis of glycoproteins. It can also act as a catalyst in enzyme processes involved in the synthesis of fatty acids and cholesterol. In skeletal and connective tissue development, manganese is involved in the process of mucopolysaccharide synthesis which is important in skeletal and cartilage structural matrix. Lack of manganese can lead to formation of abnormal cartilage and skeletal tissue, impaired connective tissue, poor muscle coordination, and impaired glucose tolerance and management of blood sugar levels. In the liver, manganese helps enzymes convert arginine to urea. In addition, manganese accompanies the enzyme pyruvate carboxylase which converts various non-carbohydrate substances into glucose for later use.

## Metal Homeostasis

Transition metals such as zinc, iron, and copper are relatively essential constituents in the sphere of protein structural stability and functionality. Despite the importance of these metals in biological functions, an overabundance or a deficit of any may issue an action that is harmful to cell growth and viability. As a result, organisms must stabilize metal levels through a homeostatic mechanism. To do this, genes that encrypt the transportation of metals and storage of proteins are often regulated at the transcriptional level when there exist a change in metal concentration.
Many studies have exposed that a bad alteration in zinc, iron, and copper can affect various cancers and diseases like Alzheimer's and Parkinson's. This leads to opportunities where metal levels might invite more complex diseases in the future. Therefore, it is crucial to develop an inclusive understanding of how metal homeostasis can uncover possibilities that are health-sustaining and potentially health-risky.

## References

1. http://drlwilson.com/Articles/IRON.htm
2. http://www.drlwilson.com/articles/copper_toxicity_syndrome.htm
3. http://www.scribd.com/doc/63209601/Cobalt-Enzymes
4. http://www.lenntech.com/periodic/elements/co.htm
5. http://jn.nutrition.org/content/130/4/715.full
6. http://www.springboard4health.com/notebook/min_manganese.html
7. Goodman, Louis S.; Alfred Goodman Gilman (1985). The Pharmacological Basis of Therapeutics, 7th Edition. New York, NY: Macmillan.
8. Kate M. Ehrensberger, Amanda J. Bird, Hammering Out Details: Regulating Metal Levels in Eukaryotes, Trends in Biochemical Sciences, Volume 36, Issue 10, October 2011.
* ↑ Goodman, Louis S. (1985). The Pharmacological Basis of Therapeutics, 7th Edition. New York, NY: Macmillan. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)