Heme catabolism catabolic

These workers have also used 3-iodopyrrole 103 to prepare the corresponding tin derivative 104 for Stille couplings to furnish 3-arylpyrroles 105 [78], These pyrrole derivatives are important for the synthesis of (i-aryl-substituted porphyrins for studies of heme catabolism. Also synthesized in this study were compounds 106 and 107 [78]. 

Fig. 1. Overview of intravascular heme catabolism. Hemoglobin, myoglobin, and other heme proteins are released into the circulation upon cellular destruction, and the heme moiety is oxidized by O2 to the ferric form (e.g., methemoglobin and metmyoglobin). Haptoglobin can bind a substantial amount of hemoglobin, but is readily depleted. Ferric heme dissociates from globin and can be bound by albumin or more avidly by hemopexin. Hemopexin removes heme from the circulation by a receptor-mediated transport mechanism, and once inside the ceU heme is transported to heme oxygenase for catabolism.

The level of a particular enzyme involved in xenobiotic metabolism can obviously affect the extent of metabolism by that enzyme. Again, competition may play a part if endogenous and exogenous substrates are both metabolized by an enzyme, as is the case with some of the forms of cytochromes P-450, which metabolize steroids, or NADPH cytochrome P-450 reductase and cytochrome b5 reductase, which are also involved in heme catabolism and fatty acid metabolism, respectively. 

In the cases of dietary heme and nonheme iron, the iron appears in the bloodstream bound to the transport protein transferrin. After its dissociation from dietary proteins by proteases, the heme is absorbed intact by the enterocyte. The heme i.s then degraded by heme oxidase. Heme oxidase catalyzes the Oj-depend-ent degradation of heme to biliverdm. Biliverdin is further degraded to bilirubin, which is excreted from the body in the bile. Heme absorption, as well as heme oxidase activity, is somewhat higher in the duodenum than in the jejunum and ileum, as determined in studies with rats. The heme catabolic pathway is shown in Figure 10,29, Most of the bilirubin in the body is not produced by the catabolism of dietary heme, but by the catabi lism of the heme present in old, or senescent, red blood cells, between 7S and 80% of the bilirubin formed in the body is derived from senescent red blood cells most of the remainder is derived from the normal turnover of the heme proteins in the liver. 

Landaw, I A, WincheH, H I. Endogenous production of carbon-14 labeled carbon monoxide An in vivo technique for the study of heme catabolism. J Nucl Med 1966 7 696-707. 

Regulation is also accomplished by compartmentaliza-tion of enzyme systems involved in anabolic and catabolic pathways into different cell organelles. For example, fatty acid synthesis occurs in the soluble fraction of the cytoplasm, whereas fatty acid oxidation takes place in mitochondria. Heme synthesis begins and is completed in mitochondria, but some of the intermediate reactions take place in the cytosol. Heme catabolism is initiated in the smooth endoplasmic reticulum. Transport of key metabolites across an organelle membrane system is also a form of regulation. 

In nonmammalian vertebrates, biliverdin is the final metabolite in heme catabolism. Transport of biliverdin is much easier than that of bilirubin because biliverdin is water-soluble. Conversion of biliverdin to bilirubin may have evolved in mammals because, unlike biliverdin, bilirubin readily crosses the placenta. In this way, the fetus can eliminate heme catabolites via the mother s circulation. However, this explanation may not be complete, since the rabbit (a placental mammal) excretes biliverdin as the major bile pigment. 

A.L. Balch (1981). Reversible migration of an axial carbene ligand into an iron-nitrogen bond of a porphyrin Implications for high oxidation states of heme enzymes and heme catabolism. J. Am. Chem. Soc. 103,4271-4273. 

The normal concentration of carboxyhaemoglobin in the blood of non-smokers is approximately 0.5%. This amount of carboxyhaemoglobin (COHb) is attributed to the endogenous production of carbon monoxide during the heme catabolism. The absorption of exogenous carbon monoxide increases the amount of the COHb in the blood. This increase is proportional to the oxide concentration in the air and to the duration of the exposure and rate of the subject oxygenation. A continuous exposure of... 

Thus, when intracellular levels of heme rise to a certain level, either by diffusion of free heme or from hemopexin-mediated transport, oxidation of proteins takes place. Free heme reportedly does not diminish GSH levels [119]. Thus, it would appear that a redox-active metal is involved. These cells are replete in ferritin and ferritin is induced as iron is released from heme catabolism. The form of metal, likely to be either Fe /Fe " ", Cu +/Cu +, Fe +-heme/Fe +-heme, is currently unknown as are the molecular sites of oxidation. Studies with ferrous and ferric che-... 

---