Fig.1
main points of the Selenium metabolism
• absorb and retain Se better from SeMet and Se yeast than from the inorganic Se salts • Selenide has a central role in Se metabolism, being the branch point of two metabolic pathways:selenoprotein production and selenoprotein excretion(排泄) • CH3SeH and [CH3]2SeH： excreted across the lungs（肺） • [CH3]3Se+ and CH3Se-GalN, excreted across the kidney（肾）
Different dose,different function
Any of these forms can support the nutritional requirements for the element; however, their bioefficacy depends on both dose and chemical form，specially the CH3SeH • 0.1–0.2 ppm as an essential micronutrient • 5 ppm becomes toxic • 55 ug/day daily allowance • 100–200 ug/day inhibit genetic damage and cancer development in human subjects • 400 ug/day upper safe limit
ቤተ መጻሕፍቲ ባይዱ
Selenium metabolism
• 经过代谢转化以后，Se在机体内分为
inorganic forms organic forms
sodium selenite:SeO32sodium selenate:SeO42Selenide:H2Se
general selenoproteins:SeCys,SeMet specific selenoproteins methylated selenides :CH3SeH 以硒为活性中心的酶：GPx，TrxR
the discovery of selenium functions
• That finding came from the Nutritional Prevention of Cancer (NPC) trial, a prospective(有预计的), doubleblinded（双盲的）,randomized（随机的）, placebo-controlled(有安慰剂对照的) trial involving 1312 patients recruited because of histories of nonmelanoma skin cancers（非黑色素瘤性皮肤癌 ） • To follow-up on that finding, the Se and Vitamin E Chemoprevention Trial (SELECT) was launched in the fall of 2001. This is a randomized, doubleblind,designed to determine whether Se (as SeMet) and vitamin E,alone or in combination, can reduce the risk of prostate cancer among 32,400 healthy men
Special about the CH3SeH
• 人体的正常血管是直线型，而肿瘤血管是螺旋形 ，血管内的血液流量变多，血液的压力变大，血 液流速快，肿瘤吸收营养的速度自然也就加快， 瘤体因此迅速疯长。人体的正常血管生长周期是 一年，而肿瘤血管的生长周期只有4天，也就是说 ，只需要4天的时间，肿瘤血管就能生长出来，破 坏人体的正常组织，直接造成病人病灶部位的疼 痛。癌细胞的转移，有两个渠道，一个是淋巴道 转移，只能转移到附近组织，所以危害相对较小 ；另外一个，危害巨大，那就是血管转移，事实 上，90%的癌症患者，都是死于血道转移，这也 是肿瘤血管造成的最大危害。 • 肿瘤血管，是癌细胞的营养通道和转移途径
• The insulinlike actions of Se include increasing glucose uptake and adenosine triphosphate generation through the activation of glycolysis, up-regulation of antiapoptotic protein Bcl-2, maintenance of mitochondrial membrane potential, stimulation of fatty acid synthesis and pentose phosphate pathway activity
Fig.2
low doses：cell proliferation
• When HL-60 cells were optimized in serumfree culture conditions to maximize the effects of Se on cell growth, low levels of Se (nmol/L) enhanced cell proliferation and up-regulated the expression of numerous cell cycle-related genes, including as c-Myc, cyclin C, proliferating cell nuclear antigen, cyclindependent kinase (CDK) 1, CDK2, CDK4, cyclin B and cyclin D2 mRNA and total cellular phosphorylated proteins
summary：selenium functions
• antioxidant protection (via selenoproteins), altered carcinogen metabolism, enhanced immune surveillance, regulation of cell proliferation and tumor cell invasion and inhibition of neoangiogenesis(血管异生) • In addition, Se has been shown to mediate a number of insulinlike（类似胰岛素）actions including the stimulation of glucose uptake and regulation of glycolysis(糖酵解), gluconeogenesis（糖异生）, fatty acid synthesis and the pentose phosphate pathway （磷酸戊糖途径）
Selenium：roles in cell proliferation and tumor cell invasion
background
• Selenium (Se), an essential trace dietary nutrient with anticarcinogenic（抑癌） potential • 氧族元素，原子序数34，相对分子量78.96 • In foods and dietary supplements:SeMet and SeCys,smaller amounts of methylated selenides are dominant forms of Se
Furthermore, when Jurkat cells were cultured in a serum-free (Sedeficient) medium, selenoenzyme activities such as GPx and TrxR decreased significantly within cells and subsequently induced cell death . Interestingly, a lipid soluble radicalscavenging antioxidant (vitamin E) but not the watersoluble antioxidants (ascorbic acid, N-acetyl cysteine and glutathione), completely blocked Se deficiencyinduced cell death, although vitamin E could no restore Sedependentenzyme activity
main points of the Selenium metabolism
• SAM是生物体内广泛存在的重要中间代谢 物质，参与体内众多重要生化反应。作为 生物体代谢的主要甲基供体 • β-lyase是一种裂合酶
the discovery of selenium functions
Schwarz发现某些天然物质能够防止大鼠食饵性坏死 Schwarz和 Foltz均证明，硒是防止食饵性肝坏死的 一种保护因子 Roctrack和 Hoekstra证明，硒是谷胱甘肽过氧化物酶 的活性成分 20世70年代初，中国克山病研究工作者发现克山病与 处于贫硒状态有关，采用硒盐之后，对克山病有预防作用 世界卫生组织（WHO）1973年确认硒是人类生命必须 14种 微量元素的第一种微量元素，缺硒会严重影响人的身体健康