322 / Biochemistry heme metabolism

Fig. 1 Molecular and biochemical basis of Friedreich s ataxia (FRDA). (a) A GAA-repeat expansion in the first intron of the FRDA gene results in decreased levels of frataxin as a result of inhibition of transcriptional elongation, (b) Alterations in mitochondrial biochemistry that are associated with reduced frataxin levels. Proposed functions for frataxin include iron binding, protection and synthesis of Fe-S clusters, providing a binding partner for ferrochetalase in heme (haem) metabolism, and providing a metabolic switch between heme metabolism and Fe-S cluster biosynthesis. In FRDA, reduction of firataxin results in lowered levels of aconitase and respiratory complexes 1,11, and 111. Cytosolic proteins that contain Fe-S clusters may also be affected. Inability to form Fe-S clusters leads to an accumulation of iron, which leads to increased free radical formation (Fenton chemistry) in these organelles. Increased free radical formation may feed back to further decrease levels of Fe-S clusters, which are known to be sensitive to oxidative stress.

Awad W. Iron and Heme Metabolism, in Devlin TM, ed. Textbook of Biochemistry with Clinical Correlations, 5th ed. New York WUey-Liss, 2002 1053-80. 

AMP is not the only metabolic dilemma for Darwin. The biosynthesis of the larger amino acids, lipids, vitamins, heme, and more run into the same problems, and there are difficulties beyond metabolism. But the other problems will not concern us here. I will now turn my attention away from biochemistry per se and focus on other issues. The scientific obstacles discussed in the last five chapters will serve as stark examples of the mountains and chasms that block a Darwinian explanation of life. 

The wide range of values of the ratio of MCD to absorption forms the basis of another practical, albeit rarely used, application in biophysical spectroscopy. Molecules with a characteristic MCD spectrum and high MCD/absorption anisotropy in a limited spectral region (heme proteins are a good example) can be detected and quantified in complex mixtures that exhibit continuous absorption and scattering of light across the spectrum, such as crude cell or tissue extracts.This use of MCD is similar to one-beam, two-wavelength absorption difference spectroscopy, which is widely used in studies of metabolism and the biochemistry of heme proteins. ... 

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