Heme oxidase

Figure 50-4. Absorption of iron. is converted to Fe + by ferric reductase, and Fe " is transported into the enterocyte by the apicai membrane iron transporter DMTl. Fieme is transported into the enterocyte by a separate heme transporter (HT), and heme oxidase (FiO) reieases Fe from the heme. Some of the intraceiiuiar Fe + is converted to Fe + and bound by ferritin. The remainder binds to the basoiaterai Fe + transporter (FP) and is transported into the biood-stream, aided by hephaestin (FiP). in piasma, Fe + is bound to the iron transport protein transferrin (TF). (Reproduced, with permission, from Ganong WF Review of Medical Physiology, 21 st ed. McGraw-Hill, 2003.)...

Heme oxidase Glutathione Lipoic acid Vitamin C Vitamin E Melatonin Coenzyme Qio Plasmalogens... 

The rate of heme degradation is controlled by the levels of active heme oxidase. Its activity is dependent upon cellular heme levels the higher the heme content, the more active is heme oxidase. 

Uroporphyrin I and coproporphyrin I will be present in the urine. In the absence of uroporphyrinogen cosynthase, hydroxymethyl bilane will spontaneously cyclyze into uroporphyrinogen I. Some of it will be oxidized to uroporphyrin I. Some will be decarboxylated by uroporphyrinogen decarboxylase to coproporphyrinogen I and then oxidized to coproporphyrin I. None of these will be degraded by heme oxidase. 

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. 

The mechanism of the acute kidney injury is thought to be multifactorial and similar to other cases of myoglobinuric renal failure [118, 121-126]. These factors include obstruction of tubules, toxic effects of the pigment or iron on renal tubular cells and altered hemodynamics in association with inhibition of the vasodilator nitric oxide by myoglobin. Experimental animals exposed to heme pigment have increases in the renal synthesis of both heme oxidase and ferritin [125]. This allows for more rapid heme degradation and greater sequestration of potentially toxic iron by the tubular cells [125]. Whether narcotics or the hypotensive, hypoxic environment associated with rhabdomyolysis interfere with these protective effects of the kidney is unknown. 

Nath KA, Balia G,VercellottlGM, Balia J, Jacob HS, Levitt, Rosenberg ME. Induction of heme oxidase is a rapid protective response in rhabdomyolysis in the rat. J Clin Invest 1992 90 267-270. 

Cobalt most often depresses the activity of enzyme including catalase, amino levulinic acid synthetase, and P-450, enzymes involved in cellular respiration. The Krebs citric acid cycle can be blocked by cobalt resulting in the inhibition of cellular energy production. Cobalt can replace zinc in a number of zinc-required enzymes like alcohol dehydrogenase. Cobalt can also enhance the kinetics of some enzymes such as heme oxidase in the liver. Cobalt interferes with and depresses iodine metabolism resulting in reduced thyroid activity. Reduced thyroid activity can lead to goiter. 

Selenium is an essential trace element and an integral component of heme oxidase. It appears to augment the antioxidant action of vitamin E to protect membrane lipids from oxidation. The exact mechanism of this interaction is not known however, selenium compounds are found in the selenium analogs of the sulfur-containing amino acids, such as cysteine and methionine. Se-cysteine is found in the active sites of the enzyme glutathione peroxidase, which acts to use glutathione to reduce organic hydroperoxides. 

Besides other occurrences of vanadium where the underlying biochemical mechanism is not understood (Rehder 1992, Mohammad et al. 2002a,b, Semiz et al. 2002, Semiz and McNeill 2002), vanadate-dependent non-heme oxidases are involved in the halogenation of organic compounds (see Section 1.2.1.7 Ohshiro etal. 2002, Sarmah et al. 2002, Tanaka et al. 2002, Ohsawa et al. 2001). Due to its high availability and its unique chemical features, more functions for vanadium as trace element may be uncovered in the future. 

The efficiency of iron absorption depends on both the bioavailability of dietary iron and iron status. Typically, 5-20% of the iron present in a mixed diet is absorbed. Dietary iron exists in two forms, heme and non-heme. Heme iron is derived from animal source food and is more bioavailable than non-heme iron, with approximately 20-30% of heme iron absorbed via endocytosis of the entire heme molecule. Iron is then released into the enterocyte by a heme oxidase. 

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