查看“︁腦硫脂”︁的源代码

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[[File:Sulfatide v2.svg|thumb|300px|腦硫脂的結構式]]

'''腦硫脂'''（英語：'''sulfatide'''，'''硫酸腦苷脂'''、'''硫苷脂'''、'''硫脂類'''、'''半乳糖酰基鞘氨醇'''/'''3-O-sulfogalactosylceramide'''、'''SM4'''、'''硫酸化半乳糖'''/'''sulfated galactocerebroside'''）屬於{{le|硫脂|Sulfolipid}}一類，具體上是"硫酸醣脂"（sulfoglycolipid）的一類，因其含[[硫酸鹽|硫酸]]基[[糖脂]]。<ref name=Eckhardt>{{Cite journal|author=Eckhardt, Matthias|title=The Role and Metabolism of Sulfatide in the Nervous System. |journal=Molecular Neurobiolog |volume=37 |issue=2-3 |pages=93–103 |date=June 2008 |pmid=18465098|doi= 10.1007/s12035-008-8022-3|url=http://0-search.proquest.com.libus.csd.mu.edu/docview/214790628?accountid=100}}</ref>腦硫脂的合成主要在[[内质网]]開始而在[[高尔基体]]結束，過程中[[神經酰胺]]轉化成[[半乳糖]]之後硫化為腦硫脂。在[[髓磷脂]]的半乳糖脂中，有1/5是腦硫脂。腦硫脂主要被發現在由[[中樞神經系統]]的[[少突膠質細胞]]及[[周围神经系统]]中，[[施旺細胞]]所產生[[髓磷脂|髓鞘]][[细胞膜]]的胞膜外片上。然而，腦硫脂也存在於[[真核生物]]組織的許多細胞之[[细胞膜]]的胞膜外片上。

因為腦硫脂是一種多功能分子，它可以在多種生物學領域中使用。除了作為膜成分，腦硫脂功能作用在{{le|蛋白質導向|protein targeting}}（靶向蛋白）、{{le|細胞粘附|Cell adhesion|細胞聚集及粘附}}、[[神经可塑性]]、[[記憶]]及"神經膠質細胞軸突的相互作用"（glial-axon interaction）等功能上。腦硫脂也作用在一些生理過程及系統上，包括[[神经系统]]、[[免疫系统]]、[[胰岛素]]分泌、[[凝血]]、[[病毒性疾病]]，及[[病原菌|細菌感染]]等。其結果是，腦硫脂或可關聯於或也能夠結合到[[腎]]組織、[[癌症]]細胞/組織、[[红血球]]細胞及[[血小板]]的表面、[[免疫系統]]中的[[CD1]]a-d細胞、許多[[細菌]]細胞、一些[[病毒]]、[[髓鞘]]、[[神經元]]，以及[[星形膠質細胞]]等組織上。
 
硫脂顯出異常的[[代谢]]或改變也與各種病理病症有關包括在[[神經病理學]]（neuropathology）上，比如[[異染性腦白質退化症]](MLD)、[[阿兹海默病]]及[[帕金森氏症]]。腦硫脂也與[[糖尿病]]，癌[[遠端轉移]]，及病毒包括[[HIV亞型|HIV-1]]（HIV-1/Subtypes of HIV）、[[甲型流感病毒]]、[[丙型肝炎]]以及[[牛痘|牛痘病毒]]（Vaccinia virus）等有關。此外，硫脂的過度顯現出與[[癫痫]]及「聽原性癲癇發作」（audiogenic seizures）以及其它[[神经系统]]裡的[[病理学|病理狀態]]有關。

過往及正在進行的研究將繼續闡明腦硫脂的多種生物學功能及其眾多的影響，且在[[病理学]]上已相關聯到腦硫脂。大多數研究利用[[模式生物|小鼠模型]]，而且[[異源性表達]]（heterologous expression）系統也被利用，包括到但不限於"Madin-Darby犬腎細胞"及[[羰基硫]]-7細胞。<ref name=Xiao>{{cite journal|last1=Xiao|first1=S|last2=Finkielstein|first2=CV|last3=Capelluto|first3=DG|title=The enigmatic role of sulfatides: new insights into cellular functions and mechanisms of protein recognition.|journal=Advances in experimental medicine and biology|date=2013|volume=991|pages=27–40|pmid=23775689}}</ref><ref name=Takahashi>{{cite journal|title=Role of sulfatide in normal and pathological cells and tissues|date=2012-08-01|doi=10.1194/jlr.r026682|language=en|journal=Journal of Lipid Research|volume=53|issue=8|url=http://www.jlr.org/content/53/8/1437|pages=1437–1450|issn=0022-2275|accessdate=2018-04-02|author=Tadanobu Takahashi, Takashi Suzuki|archive-date=2018-06-12|archive-url=https://web.archive.org/web/20180612100811/http://www.jlr.org/content/53/8/1437|dead-url=no}}</ref>

==腦硫脂歷史==
腦硫脂是第一個從人[[脑]]中分離出來的"磺胺醣脂"(sulfoglycolipid)。<!--It was named sulfatide in 1884 by [[Johann Ludwig Wilhelm Thudichum]] when he published "A Treatist of the Chemical Constitution of the Brain".<ref name= Eckhardt/> Originally, in 1933, it was first reported by Blix that sulfatide contained [[amide]] bound [[fatty acid]] and 4-sphingenine and that the [[sulfate]] of sulfatide was thought to be attached to the C6 position of [[galactose]].<ref name=Takahashi/><ref name= Suzuki/>-->於1955年再次得到"桑豪社"(Thannhauser)和"施密特"(Schmidt)支持；然而，通過[[气相色谱法]]，"山口山村"(Tamio Yamakawa)發現[[硫酸鹽]]實際上附著在[[半乳糖]]的C3位置，而不是C6位置。<ref name=Suzuki>{{Cite journal|author=Suzuki, A.|title=Tamio Yamakawa: Dawn of glycobiology. |journal=J. Biochem|volume=146 |issue=2 |pages=149–156 |date=2009 |pmid= 19651642|doi= 10.1093/jb/mvp103/}}</ref>於是，1962年，山川(Yamakawa)完成了糾正後的硫苷化合物的{{le|化學結構|chemical structure}}。<ref name=Honke>{{Cite journal|author=Honke, K.|title=Biosynthesis and biological function of sulfoglycolipids. |journal=The Japan Academy |volume=89 |issue=4 |pages=129–138 |date=2013 |pmid= 23574804|doi= 10.2183/pjab.89.129 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669731/}}</ref>

==硫脂合成與降解==
[[File:Synthesis of sulfatide.jpg|thumb|腦硫脂的合成]]

腦硫脂合成開始於[[尿苷二磷酸半乳糖]](UDP-半乳糖)與2-羥基化、或非羥基化[[神經酰胺]]之間的反應。<!--This reaction is catalyzed by [[galactosyltransferase]] (CGT), where [[galactose]] is transferred to 2-hydroxylated, or non-hydroxylated [[ceramide]], from [[UDP-galactose]].<ref name=Eckhardt>{{Cite journal|author=Eckhardt, Matthias|title=The Role and Metabolism of Sulfatide in the Nervous System. |journal=Molecular Neurobiolog |volume=37 |issue=2-3 |pages=93–103 |date=June 2008 |pmid=18465098|doi= 10.1007/s12035-008-8022-3|url=http://0-search.proquest.com.libus.csd.mu.edu/docview/214790628?accountid=100}}</ref> This reaction occurs in the luminal leaflet of the [[endoplasmic reticulum]], and its final product is GalCer, or galactocerebroside, which is then transported to the [[Golgi apparatus]].<ref name=Eckhardt/><ref name=Xiao>{{cite journal|last1=Xiao|first1=S|last2=Finkielstein|first2=CV|last3=Capelluto|first3=DG|title=The enigmatic role of sulfatides: new insights into cellular functions and mechanisms of protein recognition.|journal=Advances in experimental medicine and biology|date=2013|volume=991|pages=27–40|pmid=23775689}}</ref> Here, GalCer reacts with [[3'-Phosphoadenosine-5'-phosphosulfate|3’-phosphoadenosine-5’-phosphosulfate]] ([[PAPS]]) to make sulfatide. This reaction is catalyzed by cerebroside sulfotransferase (CST).<ref name=Eckhardt/> CST is a [[protein dimer|homodimeric]] protein that is found in the [[Golgi apparatus]].<ref name=Eckhardt/> It has been demonstrated that [[model organism|mice models]] lacking CST, CGT, or both are incapable of producing sulfatide indicating that CST and CGT are necessary components of sulfatide synthesis.<ref name=Xiao/>       
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磺酰胺類降解發生在[[溶酶体]]中。這裡，[[芳基硫酸酯酶A]]水解[[硫酸鹽]]基團。<ref name=Eckhardt/>然而，為了使該反應進能夠進行，{{le|鞘脂激活蛋白原|Prosaposin}}比如鞘糖蛋白B必須存在。<ref name=Xiao/> <!--Saposin B extracts sulfatide from the membrane, which makes it accessible to [[arylsulfatase A]].<ref name=Eckhardt/> [[Arylsulfatase A]] can then [[hydrolyze]] the sulfate group. Accumulation of sulfatide can cause [[Metachromatic Leukodystrophy]], a [[lysosomal storage disease]] and may be caused because of a defect in [[arylsulfatase A]], leading to an inability to degrade sulfatide.<ref name=Xiao/><ref name=Takahashi>{{cite journal|title=Role of sulfatide in normal and pathological cells and tissues|date=2012-08-01|doi=10.1194/jlr.r026682|language=en|journal=Journal of Lipid Research|volume=53|issue=8|url=http://www.jlr.org/content/53/8/1437|pages=1437–1450|issn=0022-2275|accessdate=2018-04-02|author=Tadanobu Takahashi, Takashi Suzuki}}</ref>
-->

==硫脂的生物學功能==
<!--Sulfatide participates in many biological systems and functions including the [[nervous system]], the [[immune system]], and in [[haemostasis]]/ [[thrombosis]].-->腦硫脂也被證明在[[腎]]臟中起了次要的作用。

===神經系統===
[[Image:Myelinated neuron.jpg|thumb|髓鞘軸突在[[透射电子显微镜]]下的圖像]]

腦硫脂是[[神经系统]]中的主要成分，並且在[[周围神经系统]]以及[[中樞神經系統]]中的[[髓磷脂|髓鞘]]中發現含有高水平的腦硫脂。<!--[[Myelin]] is typically composed of about 70 -75% [[lipids]], and sulfatide comprises 4-7% of this 70-75%.<ref name=Xiao/> When lacking sulfatide, [[myelin sheath]] is still produced around the [[axon]]s; however, when lacking sulfatide the lateral loops and part of the [[nodes of Ranvier]] are disorganized, so the [[myelin sheath]] does not function properly.<ref name=Honke/> -->因此，缺乏腦硫脂可導致肌肉無力、[[顫抖]]及[[失調|共濟失調]]。<ref name=Honke/>
<!--
Elevated levels of sulfatide are also associated with [[Metachromatic Leukodystrophy]], which leads to the progressive loss of myelin as a result of sulfatide accumulation in the [[Schwann cells]], [[oligodendrocytes]], [[astrocytes]], [[macrophages]] and [[neurons]].<ref name=Eckhardt/><ref name=Xiao/>  Elevated levels of sulfatide have also been linked to [[epilepsy]] and audiogenic seizures (seizures induced by sound), while elevated levels of anti-sulfatide antibodies in the [[Serum (blood)|serum]] have been associated with [[Multiple Sclerosis]] and [[Parkinson's]].<ref name=Xiao/>
-->
====鑑別髓鞘====
如上所述，腦硫脂主要在[[神经系统]]中的[[少突神經膠質細胞]]及[[施旺細胞]]裡被發現。<!--When [[oligodendrocytes]] are [[cellular differentiation|differentiating]], sulfatide is first evident in immature [[oligodendrocytes]].<ref name=Eckhardt/>  However, research suggests that sulfatide has a greater role than simply being a structural component of the membrane.<ref name=Eckhardt/> This is because sulfatide is [[upregulated]], i.e.there is an increase in sulfatide, prior to the [[myelin sheath]] being wrapped around the [[axon]], and experiments in cerebroside sulfotransferase (CST) deficient mice have shown that sulfatide operates as a negative regulator (inhibitor) of [[oligodendrocyte]] [[cellular differentiation|differentiation]].<ref name=Eckhardt/> Accordingly, further research has demonstrated that when sulfatide is deficient, there is a two to threefold increase in [[oligodendrocyte]] [[cellular differentiation|differentiation]], evidence providing support that sulfatide operates as a negative regulator or inhibitor of [[oligodendrocyte]] [[cellular differentiation|differentiation]].<ref name=Eckhardt/>  [[Myelination]] also appears to be stimulated by sulfatide in the [[Schwann Cells]]. Such stimulation is thought to occur through the following interactions. First, sulfatide binds to [[tenascin-R]] or [[laminin]] in the [[extracellular matrix]], which goes on to bind signaling molecules such as F3 and [[integrins]] in the [[glial]] membrane.<ref name=Eckhardt/> This causes signaling through [[C-src tyrosine kinase|c-src]]/[[fyn]] kinase. Specifically, the [[laminin]] α6β1-[[integrin]] forms a complex with [[fyn]] kinase and [[focal adhesion kinase]] that enables signaling, which, in turn, causes [[myelination]] to begin.<ref name=Eckhardt/> Sulfatide binding to [[laminin]] also causes [[C-src tyrosine kinase|c-src]]/[[fyn]] kinase activation and initiation of basement membrane formation.<ref name=Eckhardt/>
-->
====硫苷脂和髓鞘及淋巴細胞蛋白====
腦硫脂也與[[髓鞘及淋巴細胞蛋白]](MAL)有關。<!--Research has shown that [[MAL (gene)|MAL]] may be involved in [[vesicular transport]] of sulfatide and other [[myelin]] [[proteins]] and [[lipids]] to the myelinating membrane.<ref name=Takahashi/>  [[MAL (gene)|MAL]] is also believed to form membrane microdomains (small regions on the membrane with distinct structure and function) in which [[lipids]], such as sulfatide, are stabilized into [[lipid rafts]], allowing stabilization of the glial-axon junctions.<ref name=Eckhardt/>
-->
====神經膠質細胞軸突連接及信號====<!--
Sulfatide has also been shown to play a role in [[myelin]] maintenance and glial-axon signaling, which was indicated by research in older cerebroside sulfotransferase (CST)-deficient mice.<ref name=Takahashi/> These mice had [[vacuole|vacuolar]] degeneration, uncompacted myelin, and moderate [[demyelination]] of the [[spinal cord]].<ref name=Eckhardt/><ref name=Takahashi/> This occurs because improper glial-axon signaling and contact and disruption of paranodal glial-axon junctions causes improper placement and maintenance of  [[sodium]] and [[potassium]] channel clusters in the [[axons]] at the [[nodes of Ranvier]].<ref name=Takahashi/>  As a result, the maintenance of [[Nav1.6]] sodium clusters is impaired as there is a decrease in the number of clusters of [[sodium channels]] at the [[nodes of Ranvier]].<ref name=Eckhardt/> Additionally, [[Kv1.2]] channels are moved from the paranodal position to the juxtaparanodal position causing impairment of these channels; this is also associated with the loss of [[neurofascin]] 155 and [[Caspr]] clusters, which are important components of the glial-axon junction.<ref name=Eckhardt/>
-->
腦硫脂對[[周围神经系统]]的神經膠質[[轴突]]也是很重要的一種成分。<!--In [[peripheral nerves]] that are cerebroside sulfotransferase (CST) deficient, the [[nodes of Ranvier]] form enlarged axonal protrusions filled with enlarged [[Synaptic vesicle|vesicles]], and [[neurofascin]] 155 and [[Caspr]] clusters are diminished or absent.<ref name=Eckhardt/> In order to form a paranodal junction, [[Caspr]] and [[contactin]] form a complex with [[neurofascin]] 155.<ref name=Eckhardt/> It has been shown that sulfatide may be involved in the recruitment and formation of [[neurofascin]] 155 in [[lipid rafts]]; [[neurofascin]] 155 protein clusters then bring [[Caspr]] and [[contactin]] into the membrane to form the complex, which allows the formation of stable glial-axon junctions.<ref name=Eckhardt/> Consequently, sulfatide plays an important role in maintaining the paranodal glial-axon junctions, which allows for proper glial-axon interaction and signaling.<ref name=Eckhardt/><ref name=Takahashi/> Sulfatide has also been shown to be an inhibitor of [[myelin]] associated axon outgrowth, and small amounts of sulfatide have been found in [[astrocytes]] and [[neurons]], which is also indicative of its importance in glial-axon junctions.<ref name=Takahashi/>-->

====異常腦硫脂顯現====
腦硫脂的異常顯現與一些[[神經系統疾病]](neurological disorder)有所關聯。<!--As stated before, one of the major [[neurological disorders]] is [[Metachromatic Leukodystrophy]], which is caused by elevated levels of sulfatide, leading to the progressive loss of [[myelin]] as a result of sulfatide accumulation.<ref name= Xiao/><ref name=Takahashi/> High levels of sulfatide in the [[gray matter]] in the [[cerebellum]] and in the superior [[frontal lobe]] have been associated with [[Parkinson's disease]].<ref name= Xiao/> Additionally, accumulation of sulfatide in neurons causes [[audiogenic]] [[seizures]], which have been shown to be lethal in [[model organisms|mouse models]].<ref name= Xiao/> On the other hand, reduced levels of sulfatide in the [[cerebrum|cerebral]] gray and [[white matter]] have been associated with [[Alzheimer's disease]].<ref name= Xiao/><ref name= Hanx/>-->

===免疫系統===
不同類型的細胞在其表面上呈現出的[[抗原]]包括：<ref name=Takahashi/>
*[[巨噬细胞]]
*[[樹狀細胞]]
*[[肝細胞]]
*[[B细胞]]
*[[贅生物]]
*[[胸腺細胞]]
[[File:Protein CD1D PDB 1zt4.png|thumb|right|[[CD1D]]蛋白質]]

這些不同細胞類型中的每一種細胞在[[CD1]]的顯現。<ref name=Takahashi/> <!--There are 5 subtypes of [[CD1]] molecules that range from a through e. The a through d subtypes are capable of binding to sulfatide.<ref name=Xiao/> [[CD1a]], [[CD1]]b, and [[CD1]]c subtypes present lipid antigens to [[T cells]], while [[CD1d]] cells present [[lipids]], [[glycolipids]], and [[lipoproteins]] to [[Natural killer T cell|Natural Killer T-cells]]. [[CD1]] a through c cell subtypes initiate T helper type 1 and type 2 responses, and they facilitate sulfatide loading onto the surface of the cells.<ref name=Takahashi/> There are two types of cell subtypes that interact with [[CD1d]] cells: Type 1 [[Natural killer T cell|Natural Killer T- cells]] and Type 2 [[Natural killer T cell|Natural Killer T- cells]].<ref name=Xiao/> Type 2 [[Natural killer T cell|Natural Killer T-cells]] are able to recognize sulfatide/ [[CD1d]] tetramers, and as a result, they are activated by different tissues specific forms of sulfatide.  Type 2 [[Natural killer T cell|Natural Killer T-cells]] that react with sulfatide help aid in protection from [[autoimmune disease]] and ischemic reperfusion.<ref name=Takahashi/> They are capable of such protection because the Type 1 [[Natural killer T cell|Natural Killer T-cells]] can be regulated by Type 2 [[Natural killer T cell|Natural Killer T-cells]] that react with sulfatide by altering how the [[dendritic cells]] function.<ref name=Takahashi/>

Sulfatide also acts as an [[L-selectin]] and [[P-selectin]] [[ligand]], but it does not act as an E- selectin ligand.<ref name=Takahashi/> Selectins are adhesion molecules that facilitate the capture of circulating [[leukocytes]]. Sulfatide is also expressed on the surface of many types of cancer cells and tissues. Accordingly, sulfatide may function as a ligand for [[P-selectin]], which facilitates cancer [[metastasis]].<ref name=Takahashi/> Additionally, when [[L-selectin]] and sulfatide bind, [[upregulation]] of the [[chemokine]] co-receptor’s ([[CXCR4]]) expression is observed, specifically on the surfaced of [[leukocytes]].<ref name=Takahashi/>

Sulfatide may also function as a receptor for [[chemokines]], which are small chemostatic [[cytokine]]s, and they provide directional signals for [[leukocyte]] movement.<ref name=Takahashi/>-->[[趋化因子]]涉及：<ref name=Takahashi/>
*[[血管新生]]
*[[HIV亚型|HIV-1]]
*[[贅生物]][[遠端轉移]]
*[[造血作用]]
*[[移植排斥]]
*[[胚胎发育]]
<!--Sulfatide is also capable of binding to scavenger proteins found on [[macrophages]]. Such binding facilitates a macrophage’s ability to take up [[apoptotic]] cells.<ref name=Takahashi/>

[[Autoimmunity]] also affects sulfatide levels. When an enhanced [[antibody]] response against [[myelin]] lipids occurs, including sulfatide in patients with [[Multiple Sclerosis]], the [[demyelination]] process is increased significantly.<ref name=Halder>{{cite journal|last1=Halder|first1=RC|last2=Jahng|first2=A|last3=Maricic|first3=I|last4=Kumar|first4=V|title=Mini review: immune response to myelin-derived sulfatide and CNS-demyelination|journal=Neurochemical research|date=February 2007|volume=32|issue=2|pages=257–62|pmid=17006761}}</ref> When sulfatide and [[gangliosides]] are present, the proliferation or production of [[Natural killer T cell|Natural Killer-T cells]] that produce [[cytokines]] are activated. However, when [[CD1d]] deficient-mice are tested for their response to sulfatide, the same response is not seen, which indicates that in [[myelin]], sulfatide is a [[glycolipid]] that possesses [[immunodominance]].<ref name=Halder/>

Locally, the disruption of [[myelin]] due to the infiltration of [[T cells]] and [[macrophages]], results in the [[phagocytosis]] of [[myelin]] by [[microglia]] or [[macrophages]], suggesting that the [[T cells]] are presented with [[myelin]] lipids by [[CD1]] molecules at sites of inflammation.<ref name=Halder/>-->

===止血/血栓===
腦硫脂有[[凝血因子]]和抗凝血因子的兩種功能。<!--Sulfatide has anticoagulation activity when it binds to [[fibrinogen]], which prevents [[fibrinogen]] from converting to [[fibrin]]. Sulfatide also has a direct inhibitory effect on [[thrombosis]].<ref name=Takahashi/><ref name=Kyogashima>{{Cite journal|author=Kyogashima.|title=The role of sulfatide in thrombogenesis and haemostasis. |journal=Archives of Biochemistry and Biophysics |volume=426 |issue=2 |pages=157–162 |date=2004 |pmid= 15158666| doi=10.1016/j.abb.2004.02.005  |url=http://www.sciencedirect.com/science/article/pii/S0003986104000815}}</ref> On the other hand, sulfatide also helps to improve blood [[coagulation]] and [[thrombosis]]: first, sulfatide is believed to aid in thrombosis through its participation with [[factor XII|coagulation factor XII]]; second, sulfatide binding to [[annexin V]] accelerates [[coagulation]]; third, sulfatide and [[P-selectin]] interactions expressed on platelets, help to ensure stable [[platelet]] adhesion and aggregation.<ref name=Takahashi/><ref name=Kyogashima/> However, most of these conclusions have been drawn using exogenous forms of sulfatide. Consequently, additional research and experimentation on endogenous sulfatide is necessary to fully understand the role of sulfatide in [[coagulation]] and [[thrombosis]].<ref name=Kyogashima/> Sulfatide is also present in [[serum (blood)|serum]] [[lipoproteins]], which are believed to be associated with the cause and development of [[cardiovascular disease]].<ref name=Xiao/>-->

===腎臟===
腦硫脂也可以在[[腎|腎臟]]中發現。<!--Although sulfatide is not necessary for the [[kidney]]s to maintain their function and structure, it does play an active role in different aspects of the [[kidney]].<ref name=Takahashi/> For example, sulfatide is a [[ligand]] for [[L-selectin]], which is a receptor that can be found in the [[kidney]]s. Specifically, [[L-selectin]] is a [[lymphoid]] receptor, and the binding between [[L-selectin]] and sulfatide in the [[kidney]]’s interstitium plays a major role in [[monocyte]] permeation and infiltration into the [[kidney]].<ref name=Takahashi/><ref name=Honke/> Additionally, sulfatide is also found in the glandular stomach [[epithelium]] and in the apical membranes of the distal kidney tubuli where [[Myelin and lymphocyte protein]](MAL) is expressed. [[MAL (gene)|MAL]] forms complexes with sulfatide and other [[glycosphingolipids]], and these complexes have been shown to play a role in apical sorting and stabilization of sphingoglycolipid enriched areas.<ref name=Eckhardt/><ref name=Takahashi/>-->

==病理細胞和組織的作用==<!--
Sulfatide has been shown to play a role or have some association with several diseases and infections. This includes [[diabetes mellitus]], [[cancer]] and tumors, [[metachromatic leukodystrophy]], various [[bacterial infections]], and [[viruses]] including [[HIV-1]], [[Hepatitis C]], [[influenza A virus]], and [[vaccinia virus]].-->

===異染性腦白質退化症===
[[File:PDB 1auk EBI.jpg|thumb|right|[[芳基硫酸酯酶A]]]]
<!--
[[Metachromatic leukodystrophy]], also known as MLD, is a [[recessive]] [[lysosomal storage disorder]]. It is believed to be caused by a deficiency in [[arylsulfatase A]].<ref name= Eckhardt/><ref name="Whitfield 2001">{{cite journal|url=http://linkinghub.elsevier.com/retrieve/pii/S1096719201931658|pages=30–37|title=Characterization of Urinary Sulfatides in Metachromatic Leukodystrophy Using Electrospray Ionization-Tandem Mass Spectrometry|journal=Molecular Genetics and Metabolism|volume=73|issue=1|accessdate=2018-04-02|doi=10.1006/mgme.2001.3165|author=Phillip D. Whitfield, Peter C. Sharp, David W. Johnson, Paul Nelson, Peter J. Meikle}}</ref> [[Arylsulfatase A]] is a [[lysosome|lysosomal]] [[sulfatase]] that is able to hydrolyze the 3-O-sulfogalactosylceramide and 3-O-sulfolactosylceramide. Both 3-O-sulfolactosylceramide and 3-O-sulfogalactosylceramide can be located mainly in the [[central nervous system]] as well as in the [[peripheral nervous system]].<ref name= Eckhardt/> When lacking the lysosomal enzyme or [[mutations]] in the gene coding for saposin B occur, this can lead to the accumulation of [[lysosome|lysosomal sulfatide]], which then develops into [[metachromatic leukodystrophy]].<ref name= Eckhardt/><ref name=Takahashi/>
-->
腦硫脂起著[[髓鞘]]的重要作用。<!--[[Myelin]] acts as an insulating sheath that surrounds many [[nerve fibers]] and increases the speed at which impulses are conducted. When sulfatide is not distributed properly, it can affect the normal physiological conduction of electrical impulses between [[nerve cells]].<ref name= Eckhardt/> This then results in [[demyelination]] because of the buildup of sulfatide and is the main cause of [[Metachromatic Leukodystrophy]].<ref name= Eckhardt/><ref name=Takahashi/>

However, how sulfatide buildup causes demyelination and neural degeneration is still mostly unknown.<ref name= Eckhardt/> [[Metachromatic Leukodystrophy]] results in neurological manifestations that are centered on the impairment of the central nervous system and the peripheral nervous system including the following: [[seizures]], progressive coordination and speech problems, and behavioral disturbances.<ref name=Patil>{{cite journal|last1=Patil|first1=S.A|last2=Maegawa|first2=C.H|title=Developing therapeutic approaches for metachromatic leukodystrophy.|journal= Druh Design, Development and Therapy|date=2013|volume=7|pages=729–745|pmid=23966770|doi=10.2147/DDDT.S15467}}</ref> Treatment is still being studied and evaluated, but mice studies indicate that treatments including [[gene therapy]], cell based therapies using [[oligodendrocyte]] progenitors cells, [[enzyme replacement therapy]], or [[Adeno-associated virus|adeno-associated viral]] and [[Lentiviral vector in gene therapy|lentiviral]] mediated [[gene therapy]] may prove to be effective in reducing the effects of [[Metachromatic Leukodystrophy]].<ref name= Eckhardt/>-->

===糖尿病===
<!--Sulfatide has several isoforms including C16:0, which is found primarily in the [[secretory granule]]s and toward the surface of the membrane of [[β cells]]. [[Secretory granule]]s and [[β cells]] are found in the [[islet of Langerhans]] and in rat β TC3 cells.<ref name=Takahashi/> Research has shown that in the [[pancreas]]es of [[type II diabetes|type II diabetic]] [[model organism|mouse models]], there is a deficiency of C16:0. Additional research has shown that C16:0 plays an important role in assisting to improve [[insulin]] crystal preservation, and as the [[β cells]] in the [[pancreas]] secrete [[insulin]], sulfatide aids in the monomerization of [[insulin]], which is the breakdown of [[insulin]] into its basics components or [[monomers]].<ref name=Takahashi/> Consequently, sulfatide is needed in order to maintain normal [[insulin]] secretion, which sulfatide is capable of mediating through stimulation of [[calcium]] dependent [[exocytosis]] and [[Adenosine triphosphate]][[Adenosine triphosphate|(ATP)]] sensitive [[potassium ion channels]].<ref name=Takahashi/> -->磺胺類也可以刺激{{le|胰島素原|Proinsulin}}折疊，因為它可以作為[[胰岛素]]的[[分子伴侣]]。<ref name=Takahashi/>
<!--
In the diagnosis of [[type I diabetes]], elevated anti-sulfatide antibodies in [[serum (blood)|serum]] arise. Such anti-sulfatide antibodies prevent [[insulin]] [[secretion]] and [[exocytosis]].<ref name=Takahashi/> However, research has shown that when non-obese diabetic mice are treated with sulfatide, it reduces the possible occurrence of diabetes from 85% in control animals to 35% in experimental animals.<ref name=Takahashi/> Sulfatide is also commonly known to possess [[anti-inflammatory]] properties. As a result of these anti-inflammatory properties, which aid in the blockage of [[L-selectin]], sulfatide has been shown to prevent [[type I diabetes]] and inhibit [[insulitis]] in non-obese diabetic mice.<ref name=Takahashi/> Sulfatide also prevents [[apoptosis]] in insulin secreting cells by preventing the effects of [[interleukin-1 beta]] (lL-1β), [[interferon beta 1b]] (lFN-1β), and [[tumor necrosis factor alpha]] (TNF-α) that promote [[apoptosis]].<ref name=Takahashi/>

Sulfatide may also be involved in not just [[type I diabetes]], but also [[type II diabetes]]. Specifically, sulfatide is capable of inhibiting [[TNF-α]] secretion. When there are low [[serum (blood)|serum]] levels of sulfatide, as well as elevated production of [[TNF-α]] in patients that have [[type II diabetes]], it is commonly associated with [[insulin resistance]].<ref name=Takahashi/> However, sulfatide may mediate suppression of [[type II diabetes]] through the activation of potassium protein channels.<ref name=Takahashi/>-->

===癌症和腫瘤===<!--
Elevated sulfatide is common in many tissues in the human body including numerous [[cancer]] tissues and cells.<ref name=Xiao/><ref name=Takahashi/> These include:
[[File:Lung adenocarcinoma - TTF-1 - highmag.jpg|thumb|Primary Lung [[adenocarcinoma]]]]-->
*原發性[[大腸癌]]組織。
*原發性[[肺腺癌]]組織。
*惡性及良性[[卵巢癌]]組織。
*[[腎癌]]組織。
*漿液性乳頭狀卵巢癌組織。
*[[胃癌]]組織。
*腎癌（SMKT-R3細胞系）。
<!--
Sulfatide levels in these cancer lines and tissues may vary. For example, the levels of sulfatide are much lower in undifferentiated small cell [[carcinoma]] tissues and primary lung [[squamous cell carcinoma]] tissues in humans than in primary lung [[adenocarcinoma]] tissue in humans.<ref name=Takahashi/>  In human [[ovarian cancer]]s, sulfatide levels are much higher in [[malignant]] [[ovarian cancer]]s than in [[benign]] [[ovarian cancer]]s.<ref name=Xiao/><ref name=Takahashi/> Other cancers such as [[Wilms’ tumor]] show no expression of sulfatide. Therefore, it appears that such increased levels of sulfatide are not universal in every form of cancer, and more experimentation must be done to confirm that elevated levels of sulfatide are not just [[artifact (error)|artifacts]] of cultured cancer cell lines.<ref name=Takahashi/>
[[File:Pselectin.PNG|thumb|[[P-selectin]]]]
However, experimentation using [[renal cancer]] cell lines has given some insight into the mechanism for the elevated levels of sulfatide expression in cancer cells.<ref name=Takahashi/> Specifically, cerebroside sulfotransferase (CST) is elevated as it passes along a [[signaling pathway]] which involves:<ref name=Takahashi/>
*[[hepatocyte growth factor]]
*[[epidermal growth factor]]
*[[tyrosine kinases]]
*[[TNF-α]]
*[[protein kinase C]]
*[[Ras]]

This path results in the accumulation of sulfatide in [[renal cancer]] cell lines.<ref name=Takahashi/> Additionally, sulfatide can accumulate on the surface of cancer cells. This indicates that sulfatide may serve as a specific [[ligand]] for [[P-selectin]]. This would contribute to increased [[metastasis]] of the cancer.<ref name=Takahashi/> However, more research is needed to elucidate the relationship between the elevated levels of sulfatide expression and the initiation and [[metastasis]] mechanisms of cancer,<ref name=Takahashi/> but sulfatide may be a useful [[serum (blood)|serum]] [[biomarker]] for early tumor detection.<ref name=Xiao/>-->

===病毒感染===<!--
Experimentation with sulfatide has shown that it has involvement in several viral infections including [[HIV-1]], [[Influenza A virus]], [[Hepatitis C]], and the [[Vaccinia virus]].-->

====HIV-1====
[[File:PDB 1b03 EBI.jpg|thumb|right|[[V3 loop]] fragment of the [[HIV-1]] envelope [[gp120]] complex]]

磺胺類藥物顯示涉及[[HIV亚型]]的感染。<ref name=Xiao/><!--[[gp120]]-[[gp41]] are specific types of envelope [[glycoprotein]] complexes that are found on HIV-1.<ref name=Takahashi/> These glycoprotein complexes can interact with [[CD4]], a viral receptor molecule, which induces a change in the conformation of [[gp120]]. This change in conformation allows the [[gp120]] complex to interact with the [[chemokine]] co-receptor and the insertion of the fusion peptide,[[gp41]], into the membrane of the host cell.<ref name=Takahashi/> This allows the HIV-1 virus to enter into the cell.<ref name=Takahashi/> [[Gp120]] can also bind to [[glycolipids]] like sulfatide and galactocerebroside (GalCer). Sulfatide binds strongly to the [[V3 loop]] of [[gp120]], which does not interact with [[CD4]].<ref name=Takahashi/> Consequently, sulfatide acts as an alternate virus receptor in CD4- cells, and it participates in transmembrane signaling. However, sulfatide has little function in HIV-1 infection of CD4+ cells.<ref name=Takahashi/>

The binding of [[gp120]] to GalCer has the ability to start the fusion of HIV-1, but the binding of [[gp120]] to sulfatide does not.<ref name=Takahashi/> Sulfatide is not a functional receptor. However, experiments have shown that sulfatide and GalCer compete for the ability to bind to gp120, and sulfatide has been shown to have the strongest [[binding affinity]] for recombinant [[gp120]] of all the glycolipids tested.<ref name=Takahashi/>  Therefore, this suggests that when sulfatide is attached to HIV-1, it cannot interact with the [[chemokine]] co-receptor because of the instability of the complex between [[gp120]] and sulfatide, which therefore prevents the initiation of the fusion process.<ref name=Takahashi/> This indicates that sulfatide can prevent [[HIV-1]] infection by mediating [[gp120]] binding, which, in turn, prevents the fusion process; consequently, it has been demonstrated that sulfatide treatments may lead to the inhibition of HIV-1 replication.<ref name=Takahashi/>

Additionally,[[HIV-1]] infected patients often suffer from myelin degeneration in the [[central nervous system]]. These patients have elevated levels of sulfatide in the [[cerebrospinal fluid]] (CSF) and anti-sulfatide antibodies in the [[serum (blood)|serum]].<ref name=Takahashi/> Elevated levels of anti-sulfatide antibodies can cause [[demyelination]]. This is caused by the binding of the anti-sulfatide antibodies to the surface of the [[myelin sheath]] and/or the surface of [[Schwann Cells]], which then activates a complete cascade of demyelination.<ref name=Takahashi/> Also, advanced stage [[AIDS]] patients can develop [[Guillain-Barré syndrome]] (GBS). [[Guillain-Barré syndrome]] is classified as an acute [[autoimmune]] [[polyneuropathy]], which specifically affects the [[peripheral nervous system]] of the infected patient.<ref name=Takahashi/> Experimentation has shown that anti-sulfatide autoimmune antibodies may contribute to the development of [[Guillain-Barré syndrome]] in [[AIDS]] patients as well as the development of [[peripheral nervous system]] injury in [[HIV-1]] infected patients.<ref name=Takahashi/>-->

====C型肝炎====
與混合型{{le|冷球蛋白血症|Cryoglobulinemia}}（MC）相關的[[丙型肝炎]]病毒（HCV）之幾名患者在其血漿中具有升高的抗硫酸酯抗體水平。<ref name=Takahashi/><!--Mixed cryoglobulinemia (MC) is an immune disease, which typically presents with immune complex mediated [[vasculitis]] of the small vessels.<ref name=Takahashi/>  It is believed there is a relationship between HCV and MC; however, the exact role of HCV in relation to the cause of MC has not yet been fully understood or discovered.  Nevertheless, [[sphingolipid]] synthesis in the host, has been demonstrated to be necessary for HCV [[self-replication|replication]] , which indicates that sulfatide may be involved in the [[self-replication|replication]] of HCV.<ref name=Takahashi/>-->

====A型流感====
[[甲型流感病毒]]（IAV）與腦硫脂強烈地結合。<ref name=Xiao/> <!--However, sulfatide receptors have no [[sialic acid]], which has been shown to play a necessary role as a virus receptor that facilitates the binding of the [[influenza A virus]].<ref name=Takahashi/> Sulfatide has also been shown to inhibit [[influenza A virus]] sialidase activity. However, this is only under acidic conditions not neutral conditions.<ref name=Takahashi/> To fully understand the role of sulfatide in the cycle of [[Influenza A virus|IAV]] infection, research have expressed sulfatide in Madin-Darby canine kidney cells, which can express sulfatide and support [[Influenza A virus|IAV]] [[self-replication|replication]] and in [[COS]]-7 cells, which do not have the ability to express sulfatide and do not support [[Influenza A virus|IAV]] [[self-replication|replication]] sufficiently. Consequently,the [[COS]]-7 cells were [[transfected]] with galactosyltransferase and cerebroside sulfotransferase genes from the Madin-Darby canine kidney cells and used to make two cell clones with the ability to express sulfatide .<ref name=Takahashi/>

These cells were then infected with the [[Influenza A virus|IAV]] virus, and research has shown that the sulfatide enhanced cells infected with [[Influenza A virus|IAV]] show increased [[Influenza A virus|IAV]] [[self-replication|replication]] in the progeny virus, 500-3,000 times the parent virus. However, the sulfatide enriched cells also have a small reduction in initial infection compared to the parent cells.<ref name=Xiao/><ref name=Takahashi/> The opposite is shown in sulfatide [[gene knockdown|knockdown]] Madin-Darby canine kidney cells, exhibiting a reduction in progeny virus concentration vs. parent virus concentration and an increase in initial infection. Overall, such experiments demonstrate that sulfide rich cells enhance [[Influenza A virus|IAV]] [[Self-replication|replication]] and that sulfatide on the cell’s surface may play a role in the [[self-replication|replication]] of [[Influenza A virus|IAV]].<ref name=Xiao/><ref name=Takahashi/>

Further experimentation has demonstrated that sulfatide enriched cells, in which sulfatide binds to [[hemagglutinin]], enhances [[Influenza A virus|IAV]] [[self-replication|replication]] by increasing the progeny virus particle formation; this is done through the promotion of nuclear export of [[Influenza A virus|IAV]] formed viral [[ribonucleoprotein]]s from the nucleus to the cytoplasm.<ref name=Takahashi/> Experimentation has also demonstrated that if binding is inhibited between sulfatide and [[hemagglutinin]] that viral particle formation and replication would be inhibited, again suggesting that the binding between sulfatide and [[hemagglutinin]] facilitates [[Influenza A virus|IAV]] [[self-replication|replication]].<ref name=Takahashi/>-->

====牛痘病毒====
{{le|痘苗病毒|Vaccinia virus}}與已知導致[[天花]]的[[天花病毒]]密切相關。<!--The [[vaccinia virus]] has been shown to be able to bind to sulfatide through the L5 and A27 membrane proteins on the virus.<ref name=Takahashi/> It has been demonstrated in [[model organism|mouse models]] that sulfatide prevents the attachment of [[vaccinia virus]] to the cell’s surface, while also preventing death in [[model organism|mouse models]] that are typically lethal. This suggests that sulfatide may be one receptor for the [[vaccinia virus]].<ref name=Xiao/><ref name=Takahashi/>-->

===細菌感染===
腦硫脂結合到許多類的細菌及菌株，包括：<ref name=Takahashi/>
*{{le|產腸毒素大腸桿菌|Enterotoxigenic Escherichia coli}}(ETEC)TOP10菌株
*[[空腸彎曲桿菌]]
*{{le|豬肺炎支原體|Mycoplasma hyopneumoniae}}
*[[流感嗜血桿菌]]
*{{le|豬胸膜肺炎放線桿菌|Actinobacillus pleuropneumoniae}}
*[[幽門螺桿菌]]
*{{le|粘膜炎莫拉菌|Moraxella catarrhalis}}
*[[百日咳杆菌]]
*{{le|產腸毒素大腸桿菌|987P-fimbriated enterotoxigenic Escherichia coli|987P-流產性腸毒素大腸桿菌}}
*{{le|羅伊乳桿菌|Lactobacillus reuteri}} (JCM1081 及 TM105 菌株)
*{{le|人型支原體|Mycoplasma hominis}}
*{{le|支原體肺炎|Mycoplasma pneumonia}}
*[[綠膿桿菌]]
*{{le|杜克雷嗜血桿菌|Haemophilus ducreyi}}

腦硫脂作為[[糖脂]]受體，其功能是幫助將這些[[细菌]]粘附到[[黏膜]]表面。<ref name=Takahashi/><!--[[Mycoplasma hyopneumoniae]] and [[Actinobacillus pleuropneumoniae]] are [[pathogens]] that cause [[respiratory disease]] in [[swine]]. [[Haemophilus influenza]], [[Bordetella pertussis]], [[Mycoplasma pneumonia]], [[Moraxella catarrhalis]], and [[Pseudomonas aeruginosa]] cause [[respiratory disease]] in humans. Accordingly, sulfatide is located in the [[trachea]]s of both human and swine, and through the use of sulfatide present in the [[trachea]], these several bacteria are capable of adherence to the [[respiratory tract]]. [[Hsp70|Hsp-70]] on the outside of [[H. influenzae]], has also been shown to aid in the ability of this bacteria to bind to sulfatide.<ref name=Takahashi/>

[[Helicobacter pylori]], enterotoxigenic E. coli TOP10 strain, 987P-fimbriated enterotoxigenic E. coli (a strain of [[E. coli]]), and [[Lactobacillus reuteri]] are different strains of bacteria that are found to adhere to the [[gastrointestinal tract]]’s mucosal surface.<ref name=Takahashi/>  Here, sulfatide is present within the tract and is loaded from outside the tract, aiding the bacteria in adherence to the mucosa.<ref name=Takahashi/>

STb is an [[enterotoxin]] type B that is heat stable; additionally, it is secreted by the enterotoxigenic E. coli strain, and it causes diarrheal diseases in humans and many other species of animals. STb also binds strongly to sulfatide as demonstrated by its binding to sulfatide present on the mucosal surface of a pig’s [[jejunum]]. Additional experimentation suggests that sulfatide is a functional STb receptor.<ref name=Takahashi/>

Sulfatide may also play a role in [[Mycobacterium tuberculosis]], which is the agent that causes [[tuberculosis]] in humans. Experimentation suggests that sulfatide may be involved in [[Mycobacterium tuberculosis]] infection, and it may be an element of the cell wall of the bacteria [[Mycobacterium tuberculosis]].<ref name=Takahashi/>-->

==臨床意義==
===阿兹海默病的角色===
{{main|阿兹海默病}}

從[[阿兹海默病]]的早期發作階段開始，腦硫脂的含量在腦組織裡就大量的降低。<ref name=Hanx/>在阿兹海默病的溫和階段，大腦中的腦硫脂損失在[[白質]]神經組織部分可高達50％、而在[[灰质]]神經組織部分更高達90％。<ref name=Hanx/>在阿兹海默病患者的[[腦脊液]]中之腦硫脂脂濃度也是比較低的。<ref name=Hanx>{{Cite journal |author=Han, x. |title=The Pathogenic Implication of Abnormal Interaction Between Apolipoprotein E Isoforms, Amyloid-beta Peptides, and Sulfatides in Alzheimer's Disease. |journal=Molecular Neurobiology |volume=42 |issue=2-3 |pages=97–106 |date=2010 |pmid=20052565 |doi=10.1007/s12035-009-8092-x |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877150/ |access-date=2015-06-14 |archive-date=2022-04-19 |archive-url=https://web.archive.org/web/20220419145954/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877150/ |dead-url=no }}</ref> 神經元功能的特性損失伴隨著阿兹海默病並經由神經元及[[突觸]]損失而發生，且損失的是腦硫脂的脂質類。<ref name=Han/> <!--When comparing sulfatide depletion to other [[neurodegeneration|neurodegenerative diseases]], [[Alzheimer's disease]] is the only case in which sulfatide is so dramatically depleted; in [[dementia]] no marked sulfatide depletion is observed, while in [[Parkinson's disease]], sulfatide levels are dramatically elevated, and [[Multiple sclerosis]] patients only have a moderate sulfatide depletion.<ref name=Han/> -->此外，硫脂的損失被觀察到只發生在該疾病的一開始，然而在較嚴重的階段，卻極少發生額外的腦硫脂損失。<ref name=Han/>
[[File:PBB Protein APOE.jpg|thumb|[[載脂蛋白E]](ApoE/脫輔基脂蛋白E)]]

腦組織中的腦硫脂經由觀察，其中[[載脂蛋白E]](Apolipoprotein E/ApoE)已被研究過，特別是ε4"等位基因"(allele)。載脂蛋白Eε4"等位基因"是唯一已知的遺傳風險因子、明顯的表現在晚發性的[[阿兹海默病]]。<ref name=Han>{{Cite journal| author=Han, X.|title=Potential mechanisms contributing to sulfatide depletion at the earliest clinically recognizable stage of Alzheimer's disease: a tale of shotgun lipidomics.|journal=Journal of Neurochemistry|volume=103|issue=supplementary|pages=171–179|date=2007|pmid= 17986152|doi=10.1111/j.1471-4159.2007.04708.x}}</ref> 擁有載脂蛋白Eε4"等位基因"(allele)有較高風險底會生成[[阿爾茨海默氏症]]。<ref name=Han/>載脂蛋白E為涉及包括[[膽固醇]]在內的許多[[脂質]]運輸的一種蛋白，並而能調節[[中樞神經系統]]中能含有多少的腦硫脂，且介導系統的[[稳态]]結構。<ref name=Hanx/>業已發現，較高水平的載脂蛋白E與較大的腦硫脂耗損呈正相關。<ref name=Hanx/> 載脂蛋白E的相關蛋白從[[髓磷脂]]取得腦硫脂，然後降解腦硫脂成各種化合物，例如[[硫酸鹽]]。當載脂蛋白E增加時，取自[[髓磷脂]]的腦硫脂量也增加；因此，有更多的腦硫脂耗損。<ref name=Hanx/>

腦硫脂還涉入[[乙型澱粉樣蛋白]](Amyloid beta)肽的清除。乙型澱粉樣蛋白肽是[[阿兹海默病]]的標誌之一。當它們沒有適當的降低，這些肽積聚並產生斑塊，這些斑塊是乙型澱粉樣蛋白肽片的團塊，而且和[[阿兹海默病]]有相當的關聯。<ref name=Hanx/>乙型澱粉樣蛋白肽的清除是很重要的，最好要讓這種斑塊的積累現象不要出現。<ref name=Hanx/>經由[[內吞作用|內吞]]的途徑，腦硫脂可促進乙型澱粉樣蛋白肽的去除。因此，當有高含量的腦硫脂時，則就有較低量的乙型澱粉樣蛋白肽。<ref name=Hanx/>因為[[阿兹海默病|阿兹海默氏疾病]]的受試者具有較低腦硫脂水平，故而乙型澱粉樣蛋白肽的清除率較低，這使得肽在大腦裡積聚並產生斑塊。<ref name=Hanx/>

===與維生素K的關係===
[[維生素K]]已被發現與腦硫脂有所關聯。不僅在動物中，維生素K已經被觀察到影響腦裡的腦硫脂濃度，而且在細菌裡也有類似的現象。<ref name= Tsaioun/><ref name="Shearer 2008">{{cite journal|title=Metabolism and cell biology of vitamin K|pages=530–547|issn=0340-6245|journal=Thrombosis and Haemostasis|volume=100|issue=4|date=2008-10|url=https://www.ncbi.nlm.nih.gov/pubmed/18841274|accessdate=2019-02-13|author=Martin J. Shearer, Paul Newman|pmid=18841274|archive-date=2016-04-27|archive-url=https://web.archive.org/web/20160427042646/http://www.ncbi.nlm.nih.gov/pubmed/18841274|dead-url=no}}</ref>神經系統中的維生素K是負責[[酶]]的活化、諸如腦硫脂的運作，而且酶對於腦[[磷脂]]的[[生物合成]]是必需的。<ref name= Tsaioun/>當[[維生素K]][[拮抗劑]][[華法林]]被添加到動物模型系統中，腦硫脂就受損。<ref name= Tsaioun/> 然而，當維生素K被添加回系統中，腦硫脂合成就正常的運作，這表明腦硫脂的合成、維生素K是必要的因素。<ref name=Tsaioun>{{Cite journal|author=Tsaioun, k.|title=Vitamin K-dependent Proteins in the Developing and Aging Nervous System.|url=https://archive.org/details/sim_nutrition-reviews_1999-08_57_8/page/231|journal=Nutrition Reviews|volume=57|issue=8|pages=231–240|date=1999|PMID= 10518409}}</ref><ref name="Shearer 2008"/><ref name="Sundaram 1990">{{cite journal|url=http://linkinghub.elsevier.com/retrieve/pii/000398619090557F|pages=109–113|title=Regulation of sulfotransferase activity by vitamin K in mouse brain|journal=Archives of Biochemistry and Biophysics|volume=277|issue=1|accessdate=2018-04-02|doi=10.1016/0003-9861(90)90557-f|author=K.Soma Sundaram, Meir Lev|archive-date=2018-06-19|archive-url=https://web.archive.org/web/20180619051327/https://linkinghub.elsevier.com/retrieve/pii/000398619090557F|dead-url=no}}</ref>

==註釋==
{{reflist|2}}

==參見==
*[[半乳糖腦苷脂]]
*[[異染性腦白質退化症]](較高水平腦硫脂)
*[[阿兹海默病]](較低水平腦硫脂)

==外部連結==
* {{MeshName|Sulfatides}}

{{Sphingolipids}}
{{Lipid storage disorders}}

[[Category:硫酸酯]]
[[Category:糖脂]]