Heme degradation

Martinez AT (2002) Molecular biology and structure-function of lignin-degrading heme peroxidases. Enzyme Microb Technol 30 425 144... 

It may come as a surprise that CO is synthesized by the human body and has roles in human metabolism. Specifically, an enzyme that degrades heme, a constituent of hemoglobin, our oxygen-transporting protein, makes CO, which is a neurotransmitter. Much more about neurotransmitters follows in chapter 21 when we talk about the central nervous system. For the present, just understand that specialized cells known as neurons are the conduits for communication in the nervous system. Neurotransmitters are small molecules that relay information from one neuron to another. Neurotransmitter CO is made, functions, and is quickly destroyed. Personally, I find it surprising that CO has such a critical role in the nervous system. Surprised or not, there it is and there is no doubt about it. 

Morgenstem I, Klopman S, Hibbett DS (2008) Molecular evolution and diversity of lignin degrading heme peroxidases in the Agaricomycetes. J Mol Evol 66 243-257... 

It has been suggested that carbon monoxide (CO) is an activator of soluble guanylyl cyclase in Purkinje cells. Heme oxygenase-2, which degrades heme to biliverdin and releases carbon monoxide in the process, was shown to be co-localized with guanyl cyclase in rat Purkinje and granule cells with in situ hybridization histochemistry (Verma et al., 1993). 

Fig. 44.7. Overview of heme degradation. Heme is degraded to bilirubin, carried in the blood by albumin, conjugated to form the diglucuronide in the liver, and excreted in the bile. The iron is returned to the body s iron stores. RES = reticuloendothelial system RBC = red blood cells.

Bile Pigments. The oxidative degradation of heme yields open-chain tetrapyrrole as a waste product in humans and other higher animals. The yellow color of the skin in jaundice victims is caused by the presence of biluubin [635-65-4] (32, R = (CH2)2COOH). 

Mammalian sulfite oxidase is the last enzyme in the pathway for degradation of sulfur-containing amino acids. Sulfite oxidase (SO) catalyzes the oxidation of sulfite (SO ) to sulfate (S04 ), using the heme-containing protein, cytochrome c, as electron acceptor ... 

Hyjjerbilirubinaemia is an abnormality observed mainly in neonates in whom the liver is insufficiently developed to be able to detoxify the bile pigment bilirubin. This situation is known as neonatal jaundice and can sometimes become a serious disease causing neurotoxic symptoms. Bilirubin is produced by the degradation of heme [the Fe(II) complex of protoporphyrin IX] by heme oxygenase to give biliverdin, which is reduced by biliverdin reductase to... 

The biochemistry of the porphyrins and of the bile pigments is presented in this chapter. These topics are closely related, because heme is synthesized from porphyrins and iron, and the products of degradation of heme are the bile pigments and iron. 

Under physiologic conditions in the human adult, 1—2 X 10 erythrocytes are destroyed per hour. Thus, in 1 day, a 70-kg human turns over approximately 6 g of hemoglobin. When hemoglobin is destroyed in the body, globin is degraded to its constiment amino acids, which are reused, and the iron of heme enters the iron pool, also for reuse. The iron-free porphyrin portion of heme is also degraded, mainly in the reticuloendothehal cells of the liver, spleen, and bone marrow. 

When RBCs reach the end of their life span, the globin is degraded to amino acids (which are reutilized in the body), the iron is released from heme and also reutilized, and the tetrapyrrole component of heme is converted to bilirubin, which is mainly excreted into the bowel via the bile. 

Skaar EP, AH Caspar, O Schneewind (2004) IsdG and Isdl, heme-degrading enzymes in the cytoplasm of Staphylococcus aureus. J Biol Chem 279 436-443. 

Zhu W, A Wilks, I Stojiljkovic (2000) Degradation of heme in Gram-negative bacteria the product of the hemO gene of Neisseriae is a heme oxygenase. J Bacterial 182 6783-6790. 

An extracellular enzyme from Xanthomonas sp. is able to degrade poly(c -l,4-isoprene) with the production of 12-keto-4,8-dimethyltrideca-4,8-diene-l-al (Braaz et al. 2004), and functions as a heme-dependent oxygenase (Braaz et al. 2005). 

It appears that the heme/imidazole motif can be realized in metaUoporphyrins that are available in just two steps (Fig. 18.21b). However, it is not yet known how to accomplish objectives 2 and 3. It is also important to understand the mechanism of catalyst degradation during the ORR and to identify alternative functional groups that may increase catalyst stability to be useful in fuel cells, a metaUoporphyrin catalyst would probably have to retain its catalytic properties over at least 4 x 10 turnovers (about 1000 hours of operation at a turnover frequency of 1 s ), i.e., more than a hundred times longer than the most stable metaUoporphyrin catalysts reported to date. 

Oxygenation and hydroxylation of a wide variety of biological materials almost always involves the participation of a metal ion, usually iron and sometimes copper. In one unique case, tryptophane pyrrolase, the iron is present as heme (75). The only dioxygenase enzyme reaction in which a metal ion has not been implicated is one involved in the degradation of vitamin B6 (16). 

Sinclair JA Dartmouth College, Hanover, NH The effects of heavy metals on the National Institute of synthesis and degradation of heme and Environmental Health hemoproteins in the P450 superfamily Sciences (cell culture rat, chick and rabbit) ... 

Villegas, J. A. Mauk, A. G., and Vazquez-Duhalt, R., A cytochrome C variant resistant to heme degradation by hydrogen peroxide. Chem Biol, 2000. 7 pp. 237-244. 

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