Hemichromes

What happens after the met-Hb stage and how do these later degradation products affect the MR signal? 

The next step in the normal degradation pathway of hemoglobin involves transformation of methemoglobin into a low-spin forms with a greenish-hue known as hemichromes. Hemichromes can also form directly from deoxyhemoglobin without going through a methemoglobin intermediary.

Hemichromes are typically produced by the slow denaturation of methemoglobin. During this process, the H₂O molecule at the sixth coordination site is replaced by an amino acid (typically His) from a distal part (E7) of the globin chain. This oxidation process is accompanied by the release of a superoxide (O²⁻) radical with conversion of iron to a low-spin Fe(III) state that has lost its paramagnetic properties. Hemichromes thus have weak diamagnetism and their MR signal characteristics are dominated by the background material (usually water or residual serum components) within a hematoma cavity.

Heinz bodies in RBCs

The superoxide radicals produced may damage cell walls leading to lysis of erythrocytes. During certain metabolic derangements and anemias, heimchromes may precipitate in red cells to form Heinz bodies.

---

In addition to changes near the heme centers, oxidative denaturation and conformational distortions are occurring in other parts of the hemoglobin molecule. The most important of these include exposure and oxidation of previously "buried" cysteine sulfhydryl groups that disrupt contacts between the α1 and β2 globin chains. Ultimately dissociation of polypeptide chains occurs, first into αβ dimers and later into monomers. 

Finally, the heme units themselves and ultimately Fe dissociate into their individual components. Enzymatic cleavage and recycling of hemoglobin protein fragments occurs, while iron is scavenged by macrophages and glial cells and collected as ferritin and hemosiderin, the subjects of our next Q&A.

Advanced Discussion (show/hide)»

Several chemically distinct hemichromes have been identified depending on what portion of the globin chain comes in to fill the sixth iron coordination site. Some are called "reversible" hemichromes because they may be reconverted back to deoxy-Hb in vitro by treatment with mild reducing agents under anaerobic conditions. It is not clear, however, whether reversibility actually occurs in vivo. For the most part hemichrome formation should be considered an irreversible process and accompanied by relatively severe distortions in the protein tertiary structure.

Another seldom mentioned nonfunctional hemoglobin derivative produced during the denaturation of methemoglobin is sulfhemoglobin. Sulfhemoglobin is a reduced ferrous (Fe⁺²) compound with a bright green hue having one sulfur atom attached to a β carbon in the porphyrin ring. Like deoxy-Hb it has 4 unpaired electrons and is paramagnetic. It can also weakly bind O₂, but with an affinity only one-hundredth that of unmodified Hb.

---

References
     Bradley WG Jr. MR appearance of hemorrhage in the brain. Radiology 1993; 189:15-26.    
     Gomori JM, Grossman RI. Mechanisms responsible for the MR appearance and evolution of intracranial hemorrhage. Radiographics 1988; 8:427-440.     
     Pauling L, Coryell CD. The magnetic properties and structure of the hemochromogens and related substance. Proc Natl Acad Sci USA 1936; 22:159-163. 
    Wagner KR, Sharp FR, Ardizzone TD, et al. Heme and iron metabolism: role in cerebral hemorrhage. J Cerebral Blood Flow Metabolism 2003; 23:629-652.

---

Related Questions
     What are the different forms of hemoglobin and why do they have different magnetic properties?

---

←  Previous Question

Next Question  →

↑ Complete List of Questions ↑