2002 · Nicolet et al. — Fe-only hydrogenases: structure, function and evolution
Super-Abstract
This biochemistry review covers the molecular structure, catalytic mechanism, and evolutionary origins of iron-only hydrogenase enzymes — proteins that catalyse the reversible conversion between molecular hydrogen (H₂) and protons/electrons. It is a fundamental biochemistry review about enzyme structure; it has no connection to therapeutic H₂ supplementation or H₂ health effects.
Commentary
Hydrogenases are the enzymes responsible for biological H₂ metabolism — they catalyse H₂ ↔ 2H⁺ + 2e⁻. This review by Nicolet et al. focuses on the Fe-only (iron-iron) hydrogenase class, which are simpler than NiFe hydrogenases and have been extensively studied by X-ray crystallography and spectroscopy. The paper covers the unusual active site structure (an Fe centre with CO and CN coordination), proposed electron, proton, and H₂ transport pathways, and the discovery that eukaryotic genomes contain sequences homologous to Fe-hydrogenases. Despite NiFe and Fe-only hydrogenases being evolutionarily unrelated, both share a low-spin Fe active site with CO/CN ligands — a remarkable case of convergent evolution. The discussion of eukaryotic hydrogenase-like sequences is scientifically interesting (they may relate to organelle function) but does not imply any human therapeutic H₂ effect. This paper is relevant to the biochemistry underlying H₂ biology but provides no clinical or health evidence.
Key quotes
- „Hydrogenases are enzymes capable of catalyzing the oxidation of molecular hydrogen or its production from protons and electrons according to the reversible reaction: H(2)<==>2H(+)+2e(-).“ — the fundamental biochemical reaction catalysed by all hydrogenases
- „Although evolutionarily unrelated, NiFe and Fe-hydrogenases share a common, unusual feature: an active site low-spin Fe center with CO and CN coordination.“ — convergent evolution of two hydrogenase classes towards the same unusual active site chemistry
- „eukaryotic organisms contain putatively gene coding sequences that display significant homology to Fe-hydrogenases.“ — the surprising finding that eukaryotic genomes carry hydrogenase-like sequences of unknown function
Our assessment
A structural biochemistry and evolutionary review of iron-only hydrogenase enzymes. The paper contributes to the fundamental science of how biological systems handle H₂ at the molecular level, but it is not a health or supplementation study. It provides mechanistic context for H₂ biology without any clinical, nutritional, or therapeutic implications.
Study design
- Type: narrative review · Domain: structural biochemistry, enzymology, evolutionary biology · H₂ context: Fe-only hydrogenase catalysis — H₂ ↔ protons/electrons; enzyme structure and mechanism
- Scope: Fe-only hydrogenase crystal structures, active site chemistry, proposed transport pathways, evolutionary comparison with NiFe hydrogenases, eukaryotic hydrogenase-like sequences
Abstract
Hydrogenases are enzymes capable of catalyzing the oxidation of molecular hydrogen or its production from protons and electrons according to the reversible reaction: H(2)<==>2H(+)+2e(-). Most of these enzymes fall into to major classes: NiFe and Fe-only hydrogenases. Extensive spectroscopic, electrochemical and structural studies have shed appreciable light on the catalytic mechanism of hydrogenases. Although evolutionarily unrelated, NiFe and Fe-hydrogenases share a common, unusual feature: an active site low-spin Fe center with CO and CN coordination. We have recently focused our attention on Fe-hydrogenases because from structural studies by us and others, it appears to be a simpler system than the NiFe counterpart. Thus the primary hydrogen binding site has been identified and plausible, electron, proton and hydrogen pathways from and to the buried active site may be proposed from the structural data. The extensive genome sequencing effort currently under way has shown that eukaryotic organisms contain putatively gene coding sequences that display significant homology to Fe-hydrogenases. Here, we summarize the available evidence concerning the mechanism of these enzymes and carry out a structural comparison between Fe-hydrogenases and related proteins of unknown metal content from yeast, plant, worm, insect and mammals.
Source & links
Screenshot of the PubMed page
This page mirrors the published abstract (© the authors / publisher) for reference and citation. The canonical source is the PubMed record linked above. This is not medical advice.