Cytochrome biological role

Figure 9.7. Schematic representation of AHR-mediated induction of CYP1A1. (Adapted from Whitlock, J. P. Induction of cytochrome P4501A1. Annu. Rev. Toxicol. 39,103-125,1999 Ma, Q. Induction of CYP1A1. The Ahr/DRE paradigm transcription, receptor regulation, and expanding biological roles. Curr. Drug Metab. 2,149-164, 2001.)...

The elucidation of the potential biological role of NO has led to intensive work on techniques which can provide a fast, sensitive and selective detection of NO. The binding of NO to heme centres of cytochrome c [43,56], myoglobin [59], and haemoglobin [57] is the basis for NO biosensors. 

The name cytochrome bs is now generally used for a protohemoprotein which exists in high amounts in the endoplasmic reticulum of mammalian liver cells. It shows an asymmetrical a-absorption band with a peak at 556 nm and a shoulder around 560 nm in the reduced state. However, there has been some confusion about its nomenclature. This cytochrome is firmly bound to the membrane structure and reduced with NADH by a flavoprotein (cytochrome bs reductase) which is also bound to the membrane. It is solubilized by proteolytic cleavage from the membrane and has been crystallized from several sources. The molecular weight of such preparations are about 11,000. Although both primary and ternary structures of such preparations are known, its biological role is still uncertain. Earlier findings have been fully reviewed by Strittmatter (94)-... 

These are listed in Table VI 156,161-192) with their main spectral and molecular properties as well as their biological roles if they are known. Except in the cases of cytochromes 6i and 62, these microbial cytochromes are named by the position of the peak at room temperature such as cytochromes h-554, b-563, and b-667. Microbial cytochromes including type b cytochromes have been recently reviewed by Lemberg and Barrett ) as well as by Yamanaka and Okunuki 189). Only highly purified and well-characterized h type cytochromes will be described below. 

Interest in the biological role of copper has greatly increased as the recognition of its role in a number of key physiological processes has developed. These include its importance in elastin and collagen formation which prevent aneurisms, soft bones, and other defects 1,2), the requirement for copper in the taste response (3), and its requirement for cytochrome oxidase and related systems 4). Finally, there is perhaps the best known biological role of copper— its involvement in hemoglobin formation (5, 6, 7). I propose to deal exclusively with the latter, the role... 

As in many other cases in modem science the discovery of cytochrome P450 and its biological role followed a sequence of apparently not directly related findings. It started in 1958 with the description by Garfinkel and Klingenberg of a pigment in the microsomal fraction liver which was characterized by an unusual carbon monoxide absorption difference spectrum with a peak at 450 nm. This finding was made possible by the sophisticated spectrophotometiic techniques for turbid solutions developed by B. Chance at the Johnson Research Foundation in Philadelphia. A typical difference spectmm of reduced microsomes with carbon monoxide is shown in Fig. 1. 

The electron transport protein, cytochrome c, found in the mitochondria of all eukaryotic organisms, provides the best-studied example of homology. The polypeptide chain of cytochrome c from most species contains slightly more than 100 amino acids and has a molecular weight of about 12.5 kD. Amino acid sequencing of cytochrome c from more than 40 different species has revealed that there are 28 positions in the polypeptide chain where the same amino acid residues are always found (Figure 5.27). These invariant residues apparently serve roles crucial to the biological function of this protein, and thus substitutions of other amino acids at these positions cannot be tolerated. 

D.R. McMillin, Purdue University In addition to the charge effects discussed by Professor Sykes, I would like to add that structural effects may help determine electron transfer reactions between biological partners. A case in point is the reaction between cytochrome C551 and azurin where, in order to explain the observed kinetics, reactive and unreactive forms of azurin have been proposed to exist in solution (JL). The two forms differ with respect to the state of protonation of histidine-35 and, it is supposed, with respect to conformation as well. In fact, the lH nmr spectra shown in the Figure provide direct evidence that the nickel(II) derivative of azurin does exist in two different conformations, which interconvert slowly on the nmr time-scale, depending on the state of protonation of the His35 residue (.2) As pointed out by Silvestrini et al., such effects could play a role in coordinating the flow of electrons and protons to the terminal acceptor in vivo. 

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