Metalloenzyme Definition

A metalloenzyme is an enzymatic protein that has a strong link between its protein part and a metal, where the metal is embedded within the molecule. The metal is usually in the form of an ion, and its main role is to function in enzymatic reactions. The metal sometimes plays a direct role in the binding of atoms; at other times, it works to help stabilize the protein after the enzymatic reaction. Many enzymes that regulate the biological processes within the body are metalloenzymes.

Location of Metals

• Metals help in the process of electron transfers. They are located on the active sites of the enzymes, where they act as electrophiles--electron-loving substances--that pull electrons from other substances to form a bond.

Function

• Metalloenzymes require the presence of other metals in order to function in reactions. Cynthia L. Lowry and Harry Le Vine III, of Glaxo Research Laboratories, observed in 2004 that the presence of the metals helps to stabilize the protein conformations that result from the reactions. These metals work by preventing further reactivity simply because there are no other metals present to react with. Competition for the active binding site by other compounds also restricts the activity of metalloenzymes.

Types

• There are several types of metalloenzymes, including hemoglobin, alcohol dehydrogenase and cytochromes.
  The iron atom in hemoglobin is responsible for the binding of oxygen for transport throughout the body. Alcohol dehydrogenase contains zinc, which uses the NAD+ coenzyme to oxidize alcohols. The iron contained in cytochromes--membrane proteins--carries and accepts electrons in the electron transport chain. Cytochrome oxidase utilizes copper ions to transfer electrons to an oxygen molecule, from its original substrate.
  Some other metalloenzymes include phosphotransferase, which has a magnesium ion atom (Mg2+), and arginase, which has a manganese ion (Mn2+), both of which function in electron transfer.
  Carboxypeptidase A contains zinc and changes shape to connect the substrate to its active site in its enzymatic reactions.

Regulation

• Metalloenzymes are regulated by several methods, including through diet, competition with analogs and changes in pH levels.
  Dietary intake of zinc can greatly regulate, or limit, the amount and function of its metalloenzymes. Other types of metalloenzymes are limited by the dietary intake of their metals.
  Analogs are large molecules that have enzymatic activities similar to those of metalloenzymes. These analogs compete with metalloenzymes for the bond during the transition state of an enzymatic reaction. This decreases the amount of bonds available to the metalloenzymes.
  Changes in pH levels can prevent the electron exchange between the atoms and molecules involved in the enzymatic reaction. The metals would normally help to pull or conduct these electrons to their destination, but pH level changes can block this activity.

Zinc and Metalloenzymes

• Zinc plays an important role both in the activity of many vital enzymes and in the biosynthesis of protein and its uses within the body. In the presence of zinc, the body produces lactic acid, as well as the enzymes alkaline phosphatase, carbonic anhydrase and carboxypeptidase. Zinc deficiency greatly inhibits many biological processes and is responsible for growth retardation and enlarged spleen and liver. According to the American Association for the Advancement of Science and the Center for Metalloenzyme Studies, zinc's metalloenzyme role in Alzheimer's disease is a subject of research.