Heme catabolism

Pyridoxine (B ) Pyridoxal-P (PLP) Aminotransferases (transaminase) AST (GOT), ALT (GPT) 8-Aminolevulinate synthase Protein catabolism Heme synthesis MCC isoniazid therapy Sideroblastic anemia Cheilosis or stomatitis (cracking or scaling of lip borders and corners of the mouth) Convulsions... 

The mechanism of iron and heme uptake by the intestine is becoming better understood 70-72), but clearly heme-iron is more efficiently absorbed from the gastrointestinal tract than inorganic iron 73-75), and there is a receptor for heme in the duodenal brush border membrane 76). Duodenal mucosal cells efficiently catabolize heme, and iron-transferrin can be detected in the plasma of blood vessels draining the intestinal segment shortly after Fe—heme—histidine is administered (75). 

Purine Catabolism Pyrimidine Catabolism HEME BIOTRANSFORMATION... 

Catabolizes heme to yield biliverdin, carbon monoxide and free iron... 

Endogenous NO is produced almost exclusively by L-arginine catabolism to L-citrul-line in a reaction catalyzed by a family of nitric oxide synthases (NOSs) [3]. In the first step, Arg is hydroxylated to an enzyme-bound intermediate "-hydroxy-1.-arginine (NHA), and 1 mol of NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) and O2 are consumed. In the second step, N H A is oxidized to citrulline and NO, with consumption of 0.5 mol of NADPH and 1 mol of 02 (Scheme 1.1). Oxygen activation in both steps is carried out by the enzyme-bound heme, which derives electrons from NADPH. Mammalian NOS consists of an N-terminal oxy-... 

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]. 

Not only is carbon monoxide produced during catabolism of hemes, but it is also necessary for maintenance of neuronal function and cell signaling in the vasculature and therefore is present normally in the vicinity of Mb and Hb. For synthetic systems of picket-fence, pocket, or capped porphyrins, CO affinity exceeds that for O2 sometimes by many orders of magnitude. The in... 

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.

Ferro-heme-MHBP] —> Heme Oxygenase (catabolism, iron recovery)... 

After transfer of heme to MHBP, either directly from hemopexin or from the hemopexin receptor, hemopexin and the receptor both recycle to the surface to undergo further rounds of transport. The heme inside the cell requires further intracellular trafficking to deliver heme to regulatory sites and to HO-1 for catabolism to biliverdin and iron, making intracellular transport an interesting focus of future research. The biliverdin is reduced and excreted as bilirubin, and the iron released, which can also have regulatory effects, is reutilized or stored on ferritin. 

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. 

Neonatal jaundice Babies with G6PD deficiency may experience neonatal jaundice appearing one to four days after birth. The jaundice, which may be severe, results from impaired hepatic catabolism of heme or increased production of bilirubin. 

Catabolism of heme 0 = bilirubin EB = bilirubin diglucuronide E = urobilinogen QE = urobilin A = stercobilin. 

Correct answer = B. The cyclic heme molecule is oxidatively cleaved to form biliverdin. The catabolism occurs in the cells of the reticulo endothelial system, particularly the spleen, and results in the liberation of carbon monoxide. Protoporphyrinogen is an intermediate in the synthesis, not degradation, of heme. Hemo globin and tissue cytochromes are precursors of bilirubin. 

This overall sequence of reactions is important because it mimics the natural process of heme rupture during catabolism of waste heme proteins. A blood corpuscle serves, on average, a useful life of about 120 days, and heme systems which perform more dangerous functions, such as cytochrome P450 (which activates molecular oxygen and subsequently hydroxylates hydrocarbons), survive for much shorter periods. In response to an unknown... 

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