查看“SAM”的源代码

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            <strong>[[S-腺苷甲硫氨酸]]</strong>（<strong>[[S-Adenosylmethionine]]</strong>，简称<strong>[[SAM]]</strong>或<strong>[[SAMe]]</strong>）是生物体内最重要的通用<strong>[[甲基供体]]</strong>。它由[[腺苷三磷酸]]（[[ATP]]）与[[甲硫氨酸]]在[[甲硫氨酸腺苷转移酶]]（[[MAT]]）的催化下合成。[[SAM]]参与超过40种代谢反应，其核心功能是为[[DNA]]、[[RNA]]、[[蛋白质]]（尤其是[[组蛋白]]）及[[磷脂]]的[[甲基化]]提供[[甲基]]。在<strong>[[表观遗传学]]</strong>中，[[SAM]]的水平直接决定了[[组蛋白甲基转移酶]]（<strong>[[HMTs]]</strong>）和[[DNA甲基转移酶]]（<strong>[[DNMTs]]</strong>）的催化活性。因此，[[SAM]]不仅是[[单碳代谢]]的核心分子，更是连接细胞代谢状态与[[基因表达]]调控的关键信使。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[SAM]] / [[SAMe]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">通用甲基供体 · 点击展开</div>
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                    <div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">[[SAM]]分子化学结构示意图</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心催化前体：[[甲硫氨酸]] + [[ATP]]</div>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">[[CAS]]号</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">29908-03-0</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">合成酶</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[MAT1A]] / [[MAT2A]]</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">副产物</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;">[[SAH]] (抑制性)</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">398.44 g/mol</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">临床相关通路</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[单碳代谢]] / [[叶酸循环]]</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">主要代谢器官</th>
                    <td style="padding: 12px; color: #0f172a;">[[肝脏]] (约85%)</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子药理机制：甲基化的生化逻辑</h2>
    
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        [[SAM]]作为活性甲基的载体，其核心药理机制通过<strong>[[甲硫氨酸循环]]</strong>实现：
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        <li style="margin-bottom: 12px;"><strong>甲基转移反应：</strong>在[[甲基转移酶]]的催化下，[[SAM]]分子中带正电荷的[[硫原子]]将其相连的[[甲基]]释放给底物。失去甲基后的[[SAM]]转化为<strong>[[S-腺苷同型半氨酸]]</strong>（<strong>[[SAH]]</strong>）。</li>
        <li style="margin-bottom: 12px;"><strong>反馈抑制效应：</strong>[[SAH]]是甲基转移酶的强效竞争性抑制剂。细胞内<strong>[[SAM/SAH比例]]</strong>被视为衡量细胞“[[甲基化势能]]”的金标准。比例下降通常会导致[[全基因组低甲基化]]。</li>
        <li style="margin-bottom: 12px;"><strong>表观遗传耦合：</strong>[[SAM]]的浓度波动直接影响[[组蛋白H3]]（如[[H3K27me3]]）和[[DNA]]启动子区的[[CpG岛]]甲基化状态，从而在代谢水平上控制肿瘤抑制基因或癌基因的表达。</li>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">SAM代谢异常与临床关联矩阵</h2>

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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">病理领域</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">SAM 代谢特征</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义与精准干预</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[肝细胞癌]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[MAT1A]]表达下调导致SAM耗竭</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">诱发全基因组低甲基化，补充SAM可抑制早期肝癌进展。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[抑郁症]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">神经递质甲基化效率降低</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">SAM通过促进[[多巴胺]]和[[5-羟色胺]]合成发挥抗抑郁作用。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[恶性淋巴瘤]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[EZH2]]对SAM的高需求</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">靶向[[SAM结合口袋]]的药物（如[[他泽司他]]）展现高效临床获益。</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">诊疗策略：靶向单碳代谢网络</h2>
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        针对[[SAM]]代谢轴的临床应用涵盖了营养补充与精准靶向双重路径：
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        <li style="margin-bottom: 12px;"><strong>[[精准靶向]]抑制：</strong>许多新型[[组蛋白甲基转移酶]]抑制剂通过竞争性占据酶的[[SAM结合位点]]起效。这种策略在[[MLL重排]]白血病（靶向[[DOT1L]]）中取得了重要进展。</li>
        <li style="margin-bottom: 12px;"><strong>[[代谢脆弱性]]打击：</strong>部分肿瘤通过上调<strong>[[MAT2A]]</strong>来维持其高[[SAM]]需求。抑制[[MAT2A]]可特异性剥夺肿瘤细胞的甲基来源，引发严重的代谢应激。</li>
        <li style="margin-bottom: 12px;"><strong>[[联合叶酸治疗]]：</strong>在[[精准营养]]领域，维持血浆[[同型半氨酸]]低水平及充足的[[叶酸]]水平，有助于维持健康的[[SAM]]储备，预防DNA异常低甲基化引发的癌变。</li>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键相关概念</h2>
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            <li style="margin-bottom: 8px;"><strong>[[甲硫氨酸]]：</strong>[[SAM]]生成的必需氨基酸前提。</li>
            <li style="margin-bottom: 8px;"><strong>[[SAH]]：</strong>甲基转移后的副产物，也是强效的表观遗传抑制因子。</li>
            <li style="margin-bottom: 8px;"><strong>[[H3K27me3]]：</strong>[[组蛋白H3]]的抑制标记，高度依赖[[SAM]]浓度。</li>
            <li style="margin-bottom: 8px;"><strong>[[MAT2A]]：</strong>非肝组织合成[[SAM]]的关键酶，是当前的抗癌新靶点。</li>
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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span>
        
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            [1] <strong>Lu SC, Mato JM. (2012).</strong> <em>S-adenosylmethionine in liver health, injury, and cancer.</em> <strong>[[Physiological Reviews]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该文献系统阐述了SAM在肝脏代谢及肿瘤预防中的核心支柱地位。</span>
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            [2] <strong>Mato JM, et al. (2025 update).</strong> <em>Methionine metabolism and methyl donor potential in the era of epigenetic therapy.</em> <strong>[[Nature Reviews Molecular Cell Biology]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：提供了关于MAT2A抑制剂作为抗癌新药的最新临床前进展数据。</span>
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            [[SAM]] 生物代谢生态 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td>
                <td style="padding: 10px 15px; color: #334155;">[[MAT2A]]•[[EZH2]]•[[DNMT1]]•[[COMT]]•[[DOT1L]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联通路</td>
                <td style="padding: 10px 15px; color: #334155;">[[甲硫氨酸循环]]•[[叶酸代谢]]•[[多胺生物合成]]•[[转硫途径]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[GSK]]•[[Epizyme]]•[[第一三共]]•[[Agios Pharmaceuticals]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[基于SAM-SAH比例的动态表观遗传监测]]•[[MAT2A与MTAP缺失的合成致死]]•[[饮食干预对SAM浓度的调控]]</td>
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