porphyrinRing with fourValence bondIt is connected with iron atom to form four ligand chelatedcomplex compound, commonly known as heme.According to the different structure of heme cofactor, cytochrome can be divided into a, b, c and d.The cofactor of class b cytochrome isProhemeThat is, iron protoporphyrin Ⅸ.PorphyrinSide chainSubstituentFour methyl groups, twoVinylAnd two propionate groups andhemoglobin、myoglobinThe structure of child bases is the same.
The structure of class a cytochrome cofactor is heme A, which is different from protoheme in that the eighth position of porphyrin ringFormyl groupInstead of methyl group, hydroxylation is used in the second placeAlkenylInstead of vinyl.
Class d cytochrome is only found in bacteria, and its auxiliary group is iron dihydroporphyrin, which is different from other cytochromes.
The cofactor of class C cytochrome is heme, the vinyl group on its porphyrin ring andproteinIntramolecularCysteineMercapto groupAdditiveThioetherkeyCovalentcombination.The cofactors of other kinds of cytochrome areNoncovalent bondIt binds to protein.Cytochrome in reduced statevisible lightCharacteristic light in the areaAbsorption band: α band, β band, γ band (or absorption band).Generally, the α absorption band of class a cytochrome is 598~605 nm;The maximum α absorption band of class b is 556~564 nm;Class c: 550~555 nm;Type d is 600~620 nm.
historical background
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Macmunn was first in 1886Animal cellA pigment containing heme, named tissue heme, has been found in.But the mainBiochemistIt is considered an experimental error.Until 1925, Keilin confirmed the discovery of Macmunn and changed its name to cytochrome.[1]
It is distributed in eukaryotic cells (animals, plants, yeastNeurospora）Ofmitochondrial membraneAnd some bacterialCell plasma membraneOnOxidative phosphorylationElectron transfer chainCytochrome includes: Cyt aCyt a3、Cyt b、Cyt c、Cyt c1，All but Cyt c are tightly integratedMitochondrial intimaOn, Cyt c presentsWater solubilityTherefore, it is not tightly bound to the inner membrane of mitochondria.TheirRedox potential(ElectronicAffinity）Gradually increasing, its function is to transfer electrons from variousdehydrogenaseIt is systematically transmitted to molecular oxygen.Except cytochrome c, which is membranePeripheral protein, located outside the inner membrane of mitochondria, can beSalt solutionIn addition to extraction, other cytochromes are tightly bound to the mitochondrial inner membrane, requiring high concentration ofDetergentTo dissolve them.Since cytochrome c is a soluble protein and easy to obtain crystallization, it isElectronic carrierThe structure of the protein is most clearly studied.
Animal cell
Apoptosis caused by cytochrome release
Cytochrome c of higher animals consists of one of 104 amino acid residuesPeptide chainform;The molecular weight is about 13000, in the covalently bound heme cofactor;The 5th and 6th coordination bonds of iron atom arehistidineImidazolylOfNitrogen atomandmethionineThe reduced cytochrome c cannot be directly oxidized by oxygen.It catalyzes electrons fromCytochrome reductase(or bc1 complex) toCytochrome oxidase(or cytochrome aa3).The primary structure of cytochrome c in more than 80 different species and genera has been determined, and the phylogenetic map has been drawn according to its amino acid variation, which not only reveals that cytochrome c came from a common ancestor in evolution, but also can be used to estimate the possible time of the evolution of the main species and genera of organisms.Cytochrome b and c1 areCoenzyme Q– Two bands in the cytochrome c reduction systemRedoxComponents of the center.Cytochrome b is an extreme that crosses both sides of the membraneHydrophobicityProtein.For cytochrome bamino acid compositionandStructural geneOfDeoxyribonucleic acidThe (DNA) sequence study indicates that about 68% of amino acids are non-polar.The complex function of cytochrome b in the electron transport chain is not clear.Cytochrome c1The polypeptide is composed of a large hydrophilic part and a small hydrophobic part. The hydrophilic region has a heme cofactor sticking out in the water phase outside the membrane, and has a binding point with cytochrome C.Cytochrome a and a3 are also called cytochrome oxidase, whose function is to catalyze the reduction of cytochrome cOxygen moleculeOxidized.stayChemical structureHeme a and a3 are consistent.Recent studies indicate that heme a and a3 may bind to different protein subunits.Heme a3 is different from cytochrome b, c1, c and a in that the sixth coordination bond of iron atom in a3 porphyrin ring is not occupied by amino acid residues.So, it'sReductive stateHour (Fe ²+) energy and oxygencarbon monoxideDirect combination, onOxidized stateTime and energyHCN, HN3 andH2SEtc.Among these substances, oxygen is the substrate of cytochrome oxidase, and others are itsinhibitor。cyanideIts severe toxicity is due to its strong inhibition of cytochrome oxidase, which blocks theRespiration。
In plants and somealgaeAt least three cytochromes participate in the photosynthetic electron chain ofPhotoinductionOfPhotosynthetic electron transfer, acting as an electronic carrier: cytochrome b6 (orCytochrome b563）, cytochrome b3 (orCytochrome b559）AndCytochrome f(or cytochrome b552).Cytochrome f first appeared inleafIt belongs to class C cytochrome in structure, with a molecular weight of about 100000, and its α absorption peak is between 552 and 555 nm.Cytochromes b3, b6 and f are distributed asymmetricallychloroplastthylakoidClosely bound to the membraneMembrane protein。Photosynthetic bacteria, such asPurple non sulfur bacteriaOr greenPhotosynthetic bacteriaUnder the condition of no light and oxygen, their electron transfer chains are very similar to those of mitochondriarespiratory chain；In case of light andanaerobicThe electron transfer chain is composed of coenzyme Q – cytochrome c2oxidaseform.Cytochrome c2 is a water-soluble cytochrome with a molecular weight of 12000~14000.Its primary structure andMammalsCytochrome c in mitochondria is very similar, and has the typicalabsorption spectrumThe maximum absorption peak of α is 550 nm.
In addition to oxidative phosphorylation andPhotosynthetic phosphorylationIn addition to its electron transport chain, cytochrome also exists in non phosphorylated electron transport enzymes.stayAnimal tissueOfOrganelleEndoplasmic reticulumMesenteryAnd microorganisms, there are two important cytochromes:Cytochrome b5andCytochrome P-450, catalyze someLiposolubilityHydroxylation, desaturation, and oxygenation of the substrate.Microsomal cytochrome b5 isNADH-△9StearylCoenzyme AA component of the desaturation enzyme system.With a molecular weight of about 16000, it is an amphoteric membrane protein:N-endThe hydrophilic catalytic region consists of about 80 amino acid residues;C-endThe hydrophobic peptide is composed of about 40 amino acids, which plays a role in the hydrophobic internal binding of the membrane.B5 fromNADH cytochrome b5 reductase（Flavoprotein）After receiving the electron, it is transferred to stearyl coenzyme A desaturase to makestearic acidDesaturate at △ 9 bit to generateoleic acid。P-450 is also a class b cytochrome, and the auxiliary group is proheme IX.It is characterized by being able to combine with carbon monoxide in the reduced state, showing an absorption peak at 450 nm, hence its name.In liver microsomes, 5-6 different P-450 participate in somelipidMetabolism of substances (e.gsteroid, fatty acidprostaglandin）, also catalyze someForeign matterFor example, the oxidative metabolism (detoxification) of drugs and poisons.The mechanism of P-450 may be that it forms Fe ² Γ · O ² through the combination of Fe ² Γ and oxygen molecules in the auxiliary group, and then receives electrons to cause the cleavage of oxygen oxygen bondOxygen atomIt forms water with the proton, and another oxygen atom is activated and inserted into the C-H bond of the substrate to hydroxylate the substrate.This kind of reaction can cause these extraneousToxic SubstancesA series ofMetabolic reaction, eventually leading to the excretion of these substances from the body.However, sometimes the hydroxylation products of some relatively non-toxic or low toxic substances are highly toxic, such asPolycyclic aromatic hydrocarbonsThe hydroxylation product ofCarcinogen。
Transfer sequence
1. In the respiratory chain, cytochrome belongs to electron transmission rather thanHydrogen transmitter；
2. In the respiratory chain, they are arranged in Cyt b,Cyt c1，Cyt c，Cyt aa3；
3. Cyt a and Cyt a3 form a complex, Cyt aa3, which is responsible for transferring electrons from Cyt c to oxygen, so it is called cytochrome oxidase（Cytochrome C oxidase）。
Cytochrome grouping
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Spectra of various cytochromes in animals
AllAerobic organism, whether bacteria orHigher animalEven people have cytochrome, and all cytochrome have threeabsorption peak, respectively called α, β and γ peaks, as shown in the table.The wavelengths of the β and γ peaks of various reduced cytochrome are relatively close, but the wavelengths of the α peak are significantly different.According to the different wavelength of the alpha peak, the cytochrome in animals can be divided into three groups: a, b, and c. Group a includes a, a3, group b includes bK, bT, b5, P4, and group c includes c, c1.
Cytochrome containsIron porphyrinThe cofactor of cytochrome a and a3 is heme A (above figure)Polypeptide chainThe combination of right and wrongcovalent bond。The cofactors of cytochrome bT, bK, b5, P450, c and c1 are hemes. Except for cytochrome c and c1, the cofactors of other cytochromes are not bound to polypeptide chainsCovalent bonding。The heme in cytochrome c passes through the α - carbon andEnzyme proteinCysteine at position 14 and 17 of polypeptide chainamino acidResidueOf-SHConnect to form a thioether bond.exceptCytochrome a3And P450, the six iron atoms in other cytochromes can formCoordination bondThe four N atoms in the porphyrin ring and the histone amino acid at position 18 of the polypeptide chainimidazoleNitrogen and 80 positionmethionineThe sulfur atom of the residue is saturated, so it can no longer be mixed with otherLigandsOnly the sixth coordination bond of a3 and P450 is not occupied, so it can be combined with other ligands such asO2，CN-，COEtc.[1]
Figure 2 Structure of cytochrome C
oxidase
It has been determined that there are two components, a and a3, but they cannot be separated.In fact, a and a3 are combined into onemacromoleculeOfOligomer, butSubunitThe number and structure of is not clear, usually called cytochrome aa3 orCytochrome oxidase, molecular weight is about 200000, containing two molecules of heme A and two copper atoms.Two heme A and some ligandsReactivityOn the other hand, heme A of oxidized a3 is easily bound to CN - and cannot be reduced.Heme A of reduced a3 is easy to form stable complexes with CO, thus interruptingrespiratory chainOfelectron transportHowever, heme A of cytochrome a cannot bind to CO and CN -, nor to O ².[1]
C family
Both c and c1 are mitochondrial cytochromes, and their spectral properties are very similarCofactorAnd are linked to the enzyme protein in the same way.The molecular weight of c1 monomer is 38 000, and c1 is based onPOLYMERNo matter monomer or polymer, it can not react with aa3.Cytochrome c is the cytochrome with the smallest molecular weight. Due to its small molecular weight, soluble and easy to extract and purify, it has been studied more and its structure is most clear. Cytochrome c of more than 50 organisms has been determinedPrimary structure, and its advanced structure has also been studied in detail.vertebrateThe cytochrome c of c is composed of 104 residues.Plant cytochrome c consists of 112 residues.People andchimpanzeeThe cytochrome c of different organisms is exactly the same, although there are many changes in the residues of cytochrome c.But its three-dimensional structure is basically the same.[1]
Family b
Including bT, bK, b5, P450, etc. bT and bK exist in the inner membrane of mitochondriaMitochondrial respiratory chainAnd cannot combine with O2.B5 and P450 mainly exist in the endoplasmic reticulummicrosomeAs a component of mixed functional oxidase system (see "microsomal oxidation"), the reduced P450 has a maximum absorption peak (γ peak) at 450nm after combining with CO, so it is named cytochrome P450, which can combine with O ².[1]
