Date of Award

Summer 1995

Document Type

Dissertation - Restricted

Degree Name

Doctor of Philosophy (PhD)



First Advisor

Kincaid, James R.

Second Advisor

Haworth, Daniel T.

Third Advisor

Donaldson, William A.


Heme proteins are ubiquitous in nature and they are involved in different biochemical processes: oxygen transport and storage, electron transport and oxidation reactions. All aerobic organisms use oxygen for mainly three essential processes: 1) production of energy (the energy is provided to the cell by the reduction of 0, to H20 in mitochondria and stored by coupling this reaction with the production of adenosine triphosphate (ATP)). 2) oxidative reactions in biosynthesis and biodegradation of endogenous compounds (amino acids, sugars, fatty acids, etc.) or exogenous compounds (xenobiotics). 3) protection of organisms against infections - leukocytes or macrophage are able to reduce 0 2 sequentially to superoxide anion (O-), hydrogen peroxide (H20z) and hydroxyl radical (OH'). These strong oxidizing species are involved in destruction of microbes (1). Most frequently the enzymes used to activate and use oxygen, especially by mammals, are heme proteins. This is definitely a strong argument to consider iron porphyrin an effective cofactor in binding and activation of oxygen. The naturally occurring heme prosthetic groups can take several forms including heme a, heme b, heme c, heme d and their derivatives (Figure 1.1) (2a). Among them, heme b type proteins are by far the largest family and also the most extensively studied group of hemoproteins. Despite the fact that all the members of the heme b type of proteins contain the same iron porphyrin prosthetic group (protoporphyrin IX), these enzymes are able to perform distinctly different functions: reversible oxygen binding to Fe(II) for storage (myoglobin) or transport (hemoglobin), electron transfer (cytochrome c), hydroperoxide elimination (catalases and peroxidases), catalysis of chemically difficult reactions such as hydroxylation of aromatic and aliphatic hydrocarbons, N-, 0-, S-dealkylation, deaminations, dehalogenations (cytochrome P450) etc. However, because of very different structures of the protein and distal environment of the heme, heme b proteins, even those with identical iron axial ligand, can perform distinctly different biological functions (Table 1.1) (2a-e)...



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