Functional Aspects of Hemoglobin

Studies on protein-free corrinoids and model complexes have shown that increasing the steric bulkiness around the coordinated Ca atom can cause a dramatic labilization of the Co—C bond. The protein-coenzyme adduct might contain the coenzyme in a resting state and the protein in a strained state the substrate would then switch the system into a strained coenzyme and a relaxed enzyme with little thermodynamic barrier. The strained form of the coenzyme is then in labile equilibrium with base-on cobalt(II) and the free radical. " This hypothesis, that conformational changes in cobalamin can switch chemical reactions on and off, is closely analogous with the known aspects of hemoglobin function. 

Despite all these studies of proteins and synthetic models, many essential aspects of the function of myoglobin and hemoglobin, e.g. the way the protein controls the binding of ligands (02, CO, and NO), the precise structure of the Fe-ligand bonds and the structure-spin-energy relationships at the active center, are a topic of debate [2]. 

The diseases and disorders chosen for discussion and the order of presentation parallel subject matter taught in most first-year medical biochemistry. Chapters in the first part of the book, Nucleic Acids and Protein Structure, illustrate the relationships of protein structure and function with respect to collagen (Osteogenesis Imperfecta) and hemoglobin (Sickle Cell Anemia). The chapters Fragile X Syndrome and Hereditary Spherocytosis discuss key aspects of DNA and protein structure and their respective role in chromosomal and cytoskeletal structure. The chapter cardiac troponin and myocardial infarction provides an up-to-date demonstration of the usefulness of both structural proteins and enzymes as markers of cardiovascular disease, while the chapter cx Anti trypsin Deficiency discusses the important role of endogenous enzyme inhibitors. 

Schroeder, W. A., and Jones, R. T., Some aspects of the chemistry and function of human and animal hemoglobins. Fortschr. Chem. Org. Naturst. 23, 113-194 (1965). 

Metals at the active sites of metalloproteins display special properties and are generally impressively efficient in their functional roles. The metal or metals are said to be poised for catalytic action or in an entatic state, an expression first used by Vallee and Williams in their seminal paper of 1968 (2). The fine tuning or control of the peptide in many cases results in previously unobserved aspects of the coordination chemistry of the metal in question. There are many examples, almost as many as there are metalloproteins, from (in the case of Fe) the five-coordinate high-spin Fe(II) in myoglobin and hemoglobin... 

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