Biological electron transport system-Hemeprotein and Nonhemeprotein

Heme Protien :- Porphyrin+Iron-----Hemeprotein

A hemeprotein (or haemprotein; also hemoprotein or haemoprotein), or heme protein, is a protein that contains a heme prosthetic group. They are a large class of metalloproteins. The heme group confers functionality, which can include oxygen carrying, oxygen reduction, electron transfer, and other processes. Heme is bound to the protein either covalently or noncovalently bound or both.^[1]

The heme consists of iron cation bound at the center of the conjugate base of the porphyrin, as well as other ligands attached to the "axial sites" of the iron. The porphyrin ring is a planar dianionic, tetradentate ligand. The iron is typically Fe²⁺ or Fe³⁺. One or two ligands are attached at the axial sites. The porphyrin ring has 4 nitrogen atoms that bind to the iron, leaving two other coordination positions of the iron available for bonding to the histidine of the protein and a divalent atom.

Roles

• Hemeproteins have diverse biological functions including oxygen transport, which is completed via hemeproteins including hemoglobin, myoglobin, neuroglobin, cytoglobin, and leghemoglobin.
• Some hemeproteins - cytochrome P450s, cytochrome c oxidase, ligninases, catalase. and peroxidases - are enzymes. They often activate O₂ for oxidation or hydroxylation.
• Hemeproteins also enable electron transfer as they form part of the electron transport chain. Cyctochrome a, cytochrome b, and cytochrome c have such electron transfer functions.

Cytochromes :Cytochromes are iron containing hemeproteins central to which are heme groups that are primarily responsible for the generation of ATP via electron transport.

They are found either as monomeric proteins (e.g., cytochrome c) or as subunits of larger enzymatic complexes that catalyze redoxreactions.

Structure and function:-

The heme group is a highly conjugated ring system (which allows its electrons to be very mobile) surrounding a metal ion, which readily interconverts between the oxidation states. For many cytochromes, the metal ion present is that of iron, which interconverts between Fe²⁺ (reduced) and Fe³⁺ (oxidized) states (electron-transfer processes). Cytochromes are, thus, capable of performing oxidation and reduction. Because the cytochromes (as well as other complexes) are held within membranes in an organized way, the redox reactions are carried out in the proper sequence for maximum efficiency.

In the process of oxidative phosphorylation, which is the principal energy-generating process undertaken by organisms, other membrane-bound and -soluble complexes and cofactors are involved in the chain of redox reactions, with the additional net effect that protons (H⁺) are transported across the mitochondrial inner membrane. The resulting transmembrane proton gradient (protonmotive force) is used to generate ATP, which is the universal chemical energy currency of life. ATP is consumed to drive cellular processes that require energy (such as synthesis of macromolecules, active transport of molecules across the membrane, and assembly of flagella).

Types:-

Several kinds of cytochrome exist and can be distinguished by spectroscopy, exact structure of the heme group, inhibitor sensitivity, and reduction potential.

Three types of cytochrome are distinguished by their prosthetic groups:

Type	Prosthetic group
Cytochrome a	heme a
Cytochrome b	heme b
Cytochrome d	tetrapyrrolic chelate of iron[3]

The definition of cytochrome c is not defined in terms of the heme group. There is no "cytochrome e," but there is a cytochrome f, which is often considered a type of cytochrome c.

In mitochondria and chloroplasts, these cytochromes are often combined in electron transport and related metabolic pathways:

Cytochromes	Combination
a and a3	Cytochrome c oxidase ("Complex IV") with electrons delivered to complex by soluble cytochrome c (hence the name)
b and c1	Coenzyme Q - cytochrome c reductase ("Complex III")
b6 and f	Plastoquinol—plastocyanin reductase

A distinct family of cytochromes is the cytochrome P450 family, so named for the characteristic Soret peak formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (with sodium dithionite) and complexed to carbon monoxide. These enzymes are primarily involved in steroidogenesis and detoxification.

Cytochromes P450 (CYPs) are proteins of the superfamily containing heme as a cofactor and, therefore, are hemoproteins. CYPs use a variety of small and large molecules as substrates in enzymatic reactions. They are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is derived from the spectrophotometricpeak at the wavelength of the absorption maximum of the enzyme (450 nm) when it is in the reduced state and complexed with carbon monoxide.

Most CYPs require a protein partner to deliver one or more electrons to reduce the iron (and eventually molecular oxygen). Based on the nature of the electron transfer proteins, CYPs can be classified into several groups:

• Microsomal P450 systems, in which electrons are transferred from NADPH via cytochrome P450 reductase (variously CPR, POR, or CYPOR). Cytochrome b5 (cyb5) can also contribute reducing power to this system after being reduced by cytochrome b5 reductase (CYB5R).
• Mitochondrial P450 systems, which employ adrenodoxin reductase and adrenodoxin to transfer electrons from NADPH to P450.
• Bacterial P450 systems, which employ a ferredoxin reductase and a ferredoxin to transfer electrons to P450.
• CYB5R/cyb5/P450 systems, in which both electrons required by the CYP come from cytochrome b5.
• FMN/Fd/P450 systems, originally found in Rhodococcus species, in which a FMN-domain-containing reductase is fused to the CYP.
• P450 only systems, which do not require external reducing power. Notable ones include thromboxane synthase (CYP5), prostacyclin synthase (CYP8), and CYP74A (allene oxide synthase).

The most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g., insertion of one atom of oxygen into the aliphatic position of an organic substrate (RH) while the other oxygen atom is reduced to water:

RH + O₂ + NADPH + H⁺ → ROH + H₂O + NADP⁺

^{Nonheme protein-}

Iron–sulfur protein

Iron–sulfur proteins are proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron–sulfur clusters are found in a variety of metalloproteins, such as the ferredoxins, as well as NADH dehydrogenase, hydrogenases, coenzyme Q – cytochrome c reductase, succinate – coenzyme Q reductase and nitrogenase. Iron–sulfur clusters are best known for their role in the oxidation-reduction reactions of mitochondrial electron transport. Both Complex I and Complex II of oxidative phosphorylation have multiple Fe–S clusters. They have many other functions including catalysis as illustrated by aconitase, generation of radicals as illustrated by SAM-dependent enzymes, and as sulfur donors in the biosynthesis of lipoic acid and biotin. Additionally, some Fe–S proteins regulate gene expression. Fe–S proteins are vulnerable to attack by biogenic nitric oxide. In most Fe–S proteins, the terminal ligands on Fe are thiolate, but exceptions exist.

Structural motifs

In almost all Fe–S proteins, the Fe centers are tetrahedral and the terminal ligands are thiolato sulfur centers from cysteinyl residues. The sulfide groups are either two- or three-coordinated. Three distinct kinds of Fe–S clusters with these features are most common.

2Fe–2S clusters

The simplest polymetallic system, the [Fe₂S₂] cluster, is constituted by two iron ions bridged by two sulfide ions and coordinated by four cysteinylligands (in Fe₂S₂ ferredoxins) or by two cysteines and two histidines (in Rieske proteins). The oxidized proteins contain two Fe³⁺ ions, whereas the reduced proteins contain one Fe³⁺ and one Fe²⁺ ion. These species exist in two oxidation states, (Fe^III)₂ and Fe^IIIFe^II.

4Fe–4S clusters

A common motif features a four iron ions and four sulfide ions placed at the vertices of a cubane-type cluster. The Fe centers are typically further coordinated by cysteinyl ligands. The [Fe₄S₄] electron-transfer proteins ([Fe₄S₄] ferredoxins) may be further subdivided into low-potential (bacterial-type) and high-potential (HiPIP) ferredoxins. Low- and high-potential ferredoxins are related by the following redox scheme:

In HiPIP, the cluster shuttles between [2Fe³⁺, 2Fe²⁺] (Fe₄S₄²⁺) and [3Fe³⁺, Fe²⁺] (Fe₄S₄³⁺). The potentials for this redox couple range from 0.4 to 0.1 V. In the bacterial ferredoxins, the pair of oxidation states are [Fe³⁺, 3Fe²⁺] (Fe₄S₄⁺) and [2Fe³⁺, 2Fe²⁺] (Fe₄S₄²⁺). The potentials for this redox couple range from −0.3 to −0.7 V. The two families of 4Fe–4S clusters share the Fe₄S₄²⁺ oxidation state. The difference in the redox couples is attributed to the degree of hydrogen bonding, which strongly modifies the basicity of the cysteinyl thiolate ligands. A further redox couple, which is still more reducing than the bacterial ferredoxins is implicated in the nitrogenase.

Some 4Fe–4S clusters bind substrates and are thus classified as enzyme cofactors. In aconitase, the Fe–S cluster binds aconitate at the one Fe centre that lacks a thiolate ligand. The cluster does not undergo redox, but serves as a Lewis acid catalyst to convert citrate to isocitrate. In radical SAM enzymes, the cluster binds and reduces S-adenosylmethionineto generate a radical, which is involved in many biosyntheses.

3Fe–4S clusters

Proteins are also known to contain [Fe₃S₄] centres, which feature one iron less than the more common [Fe₄S₄] cores. Three sulfide ions bridge two iron ions each, while the fourth sulfide bridges three iron ions. Their formal oxidation states may vary from [Fe₃S₄]⁺ (all-Fe³⁺ form) to [Fe₃S₄]²⁻ (all-Fe²⁺ form). In a number of iron–sulfur proteins, the [Fe₄S₄] cluster can be reversibly converted by oxidation and loss of one iron ion to a [Fe₃S₄] cluster. E.g., the inactive form of aconitase possesses an [Fe₃S₄] and is activated by addition of Fe²⁺and reductant.

Other Fe–S clusters

More complex polymetallic systems are common. Examples include both the 8Fe and the 7Fe clusters in nitrogenase. Carbon monoxide dehydrogenase and the [FeFe]-hydrogenasealso feature unusual Fe–S clusters. A special 6 cysteine-coordinated [Fe₄S₃] cluster was found in oxygen-tolerant membrane-bound [NiFe] hydrogenases