Metalloenzymes

Metalloenzymes
Introduction
Metals play roles in approximately one-third of the known enzymes. Metals may be a co-factor or they may be incorporated into the molecule, and these are known as Metalloenzymes. Amino Acids in peptide linkage posses groups that can form coordinatecovalent bonds with the metal atom. The free amino and carboxy group bind to the metal affecting the enzymes structure resulting in its active conformation. Metals main function is to serve in electron transfer. Some of the metalloenzymes include hemoglobins, cytochromes, phosphotransferases, alcohol dehydrogenase, arginase, ferredoxin, and cytochrome oxidase.
Carboxypeptidase A is a zinc Metalloenzyme that breaks peptide linkages in the digestion of proteins. The zinc ion that the enzyme contains in its active site plays a key role in that function. Metalloenzymes can be regulated in several ways since they are such a diverse group. One way that metalloenzymes are regulated is, the pH level.
Metalloenzymes such as the ones containing zinc can also be regulated by diet.
The source of zinc in humans is almost entirely through diet. Without proper intake of metals such as zinc in a persons diet, the activity of the
enzyme would be inhibited.

One thing to keep in mind while studying metalloenzymes is that they are incredibly diverse and function in a multitude of important physiological processes
Active site of zinc metalloenzyme
Structure and Overview

Metalloenzymes are proteins which function as an enzyme and contain metals that are tightly bound. In proteins such as hemoglobins and cytochromes, the metal is Fe2+ or Fe3+, and it is part of the heme prosthetic group. In other metalloenzymes the metal is built into the structure of the enzyme molecule. The metal ion can not be removed with out destroying the structure of the enzyme. Metals built into the molecule include: most phosphotransferases, containing Mg2+ alcohol dehydrogenase, Zn2+ arginase, Mn2+ ferredoxin, Fe2+; and
cytochrome oxidase, Cu2+ .
Metals are usually found in the active site of the enzyme.
The metals resemble protons (H+) in that , they are electrophiles that are able
to accept an electron pair to form a chemical bond. In this aspect, metals may act as general acids to react with anionic and neutral ligands. Metal's larger size relative to protons is compensated for by their ability to react with more than one ligand, typically react with two, four, or six ligands. If a metal is bound with two ligands it will form a linear complex. If the metal reacts with four ligands the metal will be set in the center of a square that is planer or it will form a tetrahedral structure. when six ligands react, the metal sits in the center of an octahedron.
Iron complex of heme, in which Fe forming tetrahedral
Amino acids in their peptide linkage, possess groups with the ability to bind to
the metal resulting in coordinate-covalent bonds. The free amino and carboxyl groups in a protein can bind to the metal and this
may bind the protein to a specific, active conformation.

The fact that metals bind to several ligands is important in that metals play a role in bringing remote parts of the amino acid sequence together and help
establish an active conformation of the enzyme.

Zinc is the metal incorporated in Carboxypeptidase A. The zinc atom serves as a metal ion catalyst and promotes hydrolysis. The substrate fits into the hydrophobic pocket in Carboxypeptidase A and zinc binds to the carboxyl group of the substrate to help stabilize the enzymesubstrate complex.
In this example the zinc ion acts a generalized acid and stabilizes the developing O- as water attacks the carbonyl. Zinc can also perform a different role in enzymes like the role it performs in carbonic anhydrase. Here the metal binds H2O and makes it acidic enough to lose a proton and form a Zn-OH group. The zinc metal serves as a nucleophile to the substrate. Since zinc has the ability to act as an electrophile or as the source of a nucleophilic group it is incorporated and used by many enzymes.
FUNCTIONS OF METALLOENZYMES
Hemoglobins A four-subunit molecule, containing a iron atom in each subunit, in which each subunit binds a single molecule of oxygen. Hemoglobin transports
oxygen from the lungs to the capillaries of the tissue.

Cytochromes Cytochromes are integral membrane proteins. Cytochromes contain iron
which serves to carry electrons between two segments of the electrontransport chain. The iron is reversibly oxidizable and serves as the actual electron acceptor for the cytochrome. Phosphotransferase The Mg2+ atom serves again in electron transfer.
Alcohol Dehydrogenase A zinc metalloenzyme with broad specificity. They oxidize a range of aliphatic and aromatic alcohols to their corresponding aldehydes and ketones using NAD+ as a coenzyme. Arginase
The metal atom of Mn2+ is used in electron transfer.

Ferredoxin An e- transferring proteins involved in one-electron transfer processes.
Cytochrome Oxidase
The copper ions easily accommodate electron removed from a substrate and can just as easily transfer them to a molecule of oxygen Carboxypeptidase A Carboxypeptidase A is an exopeptidase which hydrolyzes the oligopeptides one at a time from the C-terminal end of the polypeptide chain.

Metalloenzymes

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Metalloenzymes

enzyme would be inhibited.

Active site of zinc metalloenzyme

Structure and Overview

cytochrome oxidase, Cu2+ .

Metals are usually found in the active site of the enzyme.

Iron complex of heme, in which Fe forming tetrahedral

may bind the protein to a specific, active conformation.

establish an active conformation of the enzyme.

oxygen from the lungs to the capillaries of the tissue.

The metal atom of Mn2+ is used in electron transfer.

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