血红素是血红蛋白必不可少的组成部分，其生物合成与降解是生物体中最重要的代谢途径之一。血红素的生物合成过程需要经历八个酶促反应（图1），主要分为以下四个阶段：

1.δ-氨基乙酰戊酸（ALA）的生成

    δ-氨基乙酰丙酸合成酶（ALAS）催化甘氨酸和琥珀酰辅酶A缩合，生成δ-氨基乙酰戊酸（ALA）^[1]。

2.胆色素原（PBG）的生成

    在ALA脱水酶（ALAD）作用下，两分子ALA脱水缩合生成胆色素原（PBG）^[2]。

3.尿卟啉原Ⅲ（Uro III）和粪卟啉原Ⅲ（Copro III）的生成

    四分子PBG经卟啉原脱氨酶（PBGD）催化生成不稳定的羟甲基胆素（HMB）^[3]，HMB在尿卟啉原III合成酶（UROS）作用下，进一步环化为尿卟啉原Ⅲ（Uro III）^[4]，当无UROS存在时，HMB会环化为尿卟啉原I^[5]。Uro III再经尿卟啉原III脱羧酶（UROD）催化，四个乙酸侧链脱羧变成甲基，生成粪卟啉原III（Copro III）^[6]。

4.血红素的生成

    在粪卟啉原III氧化酶（CPO）作用下，Copro III转化成原卟啉原IX^[7,8]，再经原卟啉原氧化酶（PPO）催化脱氢生成原卟啉IX（PPIX）^[9,10]，最后在亚铁螯合酶（FC）催化下和亚铁离子结合，生成血红素^[11]。     血红素加氧酶（HO）是血红素降解代谢过程中的限速酶^[12]。这种酶能将血红素降解为一氧化碳（CO）、游离铁和胆绿素，其中胆绿素通过胆绿素还原酶（BR）进一步转化为胆红素^[13]。胆红素是胆汁中的主要色素，当胆红素进入肝脏后，经UDP葡糖醛酸转移酶（UGT1A1）催化，生成葡萄糖醛酸胆红素^[14]，最终在肠道微生物作用下，转化成胆素原、粪胆素原和尿胆素原（图2），随粪便排出体外。     百灵威可提供10种Frontier品牌血红素的生物合成与降解所需产品，助力该领域科学研究。

血红素的生物合成相关化合物

    由于卟啉原中间体不稳定，在空气中易氧化为相应的卟啉类似物，所以Frontier提供的是与卟啉原相对应的卟啉化合物。

血红素的降解相关化合物

参考文献

1. Ferreira, G.C., Gong, J. 5-Aminolevulinate synthase and the first step of heme biosynthesis. J Bioenerg Biomembr 27, 151–159 (1995).
2. Jaffe, E.K. Porphobilinogen synthase, the first source of Heme’s asymmetry. J Bioenerg Biomembr 27, 169–179 (1995).
3. Grandchamp, B., De Verneuil, H., Beaumont, C., Chretien, S., Walter, O. and Nordmann, Y. (1987), Tissue-specific expression of porphobilinogen deaminase. European Journal of Biochemistry, 162: 105-110.
4. Battersby, A., Fookes, C., Matcham, G. et al. Biosynthesis of the pigments of life: formation of the macrocycle. Nature 285, 17–21 (1980).
5. Paul R. Ortiz de Montellano (2008). “Hemes in Biology”. Wiley Encyclopedia of Chemical Biology. John Wiley & Sons.
6. Straka, J.G., Kushner, J.P Purification and characterization of bovine hepatic uroporphyrinogen decarboxylase. Biochemistry 1983, 22, 20, 4664-4672.
7. T. Yoshinaga, S. Sano Coproporphyrinogen oxidase: I. Purification, properties, and activation by phospholipids. J. Biol. Chem., 255 (10) (1980), pp. 4722-4726.
8. T. Yoshinaga, S. Sano Coproporphyrinogen oxidase: II. Reaction mechanism and role of tyrosine residues on the activity. J. Biol. Chem., 255 (10) (1980), pp. 4727-4731.
9. Dailey HA. 1990. Conversion of coproporphyrinogen to protoheme in higher eukaryotes and bacteria: Terminal three enzymes. In Biosynthesis of heme and chlorophylls (ed. Dailey HA), pp. 123–161. McGraw-Hill, New York.
10. Dailey, T. A. & Dailey, H. A. Human protoporphyrinogen oxidase: Expression, purification, and characterization of the cloned enzyme. Protein Sci. 5, 98–105 (1996).
11. Lecerof, D.; Fodje, M.; Hansson, A.; Hansson, M.; Al-Karadaghi, S. (March 2000). “Structural and mechanistic basis of porphyrin metallation by ferrochelatase”. Journal of Molecular Biology. 297 (1): 221–232.
12. Kikuchi G, Yoshida T, Noguchi M (2005). “Heme oxygenase and heme degradation”. Biochem. Biophys. Res. Commun. 338 (1): 558–567.
13. Ahmad Z, Salim M, Maines MD (Mar 2002). “Human biliverdin reductase is a leucine zipper-like DNA-binding protein and functions in transcriptional activation of heme oxygenase-1 by oxidative stress”. The Journal of Biological Chemistry. 277 (11): 9226–32..
14. Jansen, P.L.M., Mulder, G.J., Burchell, B. and Bock, K.W. (1992), New developments in glucuronidation research: Report of a workshop on “Glucuronidation, its role in health and disease”. Hepatology, 15: 532-544.

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用于催化的卟啉衍生物