Biological Activation of Hydrogen

The biological activation of hydrogen in organic compounds, forming, as it does, the first step in biological oxidations, is a vast field, which we cannot attempt to review here. The few remarks that follow are only intended to relate this field to the activation of hydrogen by metals, as it is quite likely that there is a common basis for catalytic activity in the two cases. 

Wieland (117) showed that dehydrogenation was the first stage in the enzymatic oxidation of organic molecules. Thus, palladium black catalyzed the oxidation of ethyl alcohol not only by oxygen but also anaerobically by quinone or methylene blue. The palladium black could be replaced by dehydrogenases, and the first step is clearly 

It is now known that the enzyme may be separated by dialysis into a coenzyme and a protein. The protein is the true catalyst and is specific for each substrate. Its function is to combine with both substrate and coenzyme, when it can mobilize the hydrogen for transfer from the one to the other. The combinations are supposedly reversible, and have been described by two equilibrium constants D and d (118). 

Protein -f-Coonzymcr Protein-Coenzyme, D Protein-Coenzyme-t-Substrate Protein-Coenzyme-Substrate, d 

A first order velocity constant, k, served to describe the actual hydrogen transfer within the complex. 

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Happe RP, RoseboomW, Pierik AJ, et al. 1997. Biological activation of hydrogen. Nature 385 126. 

Oya, Y, Yamamoto, K. Tonomura, A. (1986) The biological activity of hydrogen peroxide I. Induction of chromosome-type aberrations susceptible to inhibition by scavengers of hydroxyl radicals in human embryonic fibroblasts. Mutat. Res., 172, 245-253... 

Oya Y, Yamamoto K, Tonomura A The Biological Activity of Hydrogen Peroxide. 1. Induction of Chromosome-type Aberrations Susceptible to Inhibition by Scavangers of Hydroxyl Radicals in Human Embryonic Fibroblasts. Mutat. Res. 1986 172(3) 245-53. 

Biological activation of hydrogen in hydrogenases mimics organometallic chemistry (and vice versa) in that acceptor ligands such as CO are used to control... 

The Hydrogen-Oxygen Reaction Biological Activation of Hydrogen General Conclusions... 

Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

J. J. Chessick and A. C. Zettlemoyer The Catalytic Activation of Hydrogen in Homogeneous, Heterogeneous, and Biological Systems J. Halpern... 

Thus, the biological activity of a drug molecule could be expressed as a function of its electronic, hydrophobic, and steric properties, and one or more such factors as hydrogen bonding or polarizability (x) which might be involved. 

Tocopherol can be produced as the pure 2R,4 R,8 R stereoisomer from natural vegetable oils. This is the most biologically active of the stereoisomers. The correct side-chain stereochemistry can be obtained using a process that involves two successive enantioselective hydrogenations.28 The optimum catalyst contains a 6, 6 -dimethoxybiphenyl phosphine ligand. This reaction has not yet been applied to the enantioselective synthesis of a-tocopherol because the cyclization step with the phenol is not enantiospecific. 

Alterations in blood heme metabolism have been proposed as a possible indicator of the biological effects of hydrogen sulfide (Jappinen and Tenhunen 1990), but this does not relate to the mechanism of toxicity in humans. The activities of the enzymes of heme synthesis, i.e., delta-aminolevulinic acid synthase (ALA-S) and heme synthase (Haem-S), were examined in 21 cases of acute hydrogen sulfide toxicity in Finnish pulp mill and oil refinery workers. Subjects were exposed to hydrogen sulfide for periods ranging from approximately 1 minute to up to 3.5 hours. Hydrogen sulfide concentrations were considered to be in the range of 20-200 ppm. Several subjects lost consciousness for up to 3 minutes. 

A number of different molecular mechanisms can underpin the loss of biological activity of any protein. These include both covalent and non-covalent modification of the protein molecule, as summarized in Table 6.5. Protein denaturation, for example, entails a partial or complete alteration of the protein s three-dimensional shape. This is underlined by the disruption of the intramolecular forces that stabilize a protein s native conformation, namely hydrogen bonding, ionic attractions and hydrophobic interactions (Chapter 2). Covalent modifications of protein structure that can adversely affect its biological activity are summarized below. 

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