Department of Analytical Chemistry, Medical University of Bialystok, Bialystok, Poland.
Toxicol Mech Methods. 2003;13(4):277-93. doi: 10.1080/713857189.
Methanol, when introduced into all mammals, is oxidized into formaldehyde and then into formate, mainly in the liver. Such metabolism is accompanied by the formation of free radicals. In all animals, methanol oxidation, which is relatively slow, proceeds via the same intermediary stages, usually in the liver, and various metabolic systems are involved in the process, depending on the animal species. In nonprimates, methanol is oxidized by the catalase-peroxidase system, whereas in primates, the alcohol dehydrogenase system takes the main role in methanol oxidation. The first metabolite (formaldehyde is rapidly oxidized by formaldehyde dehydrogenase) is the reduced glutathione (GSH)-dependent enzyme. Generated formic acid is metabolized into carbon dioxide with the participation of H 4 folate and two enzymes, 10-formyl H 4 folate synthetase and dehydrogenase, whereas nonprimates oxidize formate efficiently. Humans and monkeys possess low hepatic H 4 folate and 10-formyl H 4 folate dehydrogenase levels and are characterized by the accumulation of formate after methanol intoxication. The consequences of methanol metabolism and toxicity distinguish the human and monkey from lower animals. Formic acid is likely to be the cause of the metabolic acidosis and ocular toxicity in humans and monkeys, which is not observed in most lower animals. Nevertheless, chemically reactive formaldehyde and free radicals may damage most of the components of the cells of all animal species, mainly proteins and lipids. The modification of cell components results in changes in their functions. Methanol intoxication provokes a decrease in the activity and concentration of antioxidant enzymatic as well as nonenzymatic parameters, causing enhanced membrane peroxidation of phospholipids. The modification of protein structure by formaldehyde as well as by free radicals results changes in their functions, especially in the activity of proteolytic enzymes and their inhibitors, which causes disturbances in the proteolytic-antiproteolytic balance toward the proteolytics and enhances the generation of free radicals. Such a situation can lead to destructive processes because components of the proteolytic-antiproteolytic system during enhanced membrane lipid peroxidation may penetrate from blood into extracellular space, and an uncontrolled proteolysis can occur. This applies particularly to extracellular matrix proteins.
甲醇进入所有哺乳动物体内后，会被氧化成甲醛，然后再氧化成甲酸盐，主要在肝脏中进行。这种代谢过程伴随着自由基的形成。在所有动物中，甲醇的氧化速度相对较慢，通常在肝脏中通过相同的中间阶段进行，并且不同的代谢系统参与其中，具体取决于动物种类。在非灵长类动物中，甲醇通过过氧化氢酶-过氧化物酶系统氧化，而在灵长类动物中，主要由醇脱氢酶系统参与甲醇氧化。第一个代谢产物（甲醛迅速被甲醛脱氢酶氧化）是还原型谷胱甘肽（GSH）依赖性酶。生成的甲酸在 H 4 叶酸和两种酶（10-甲酰基 H 4 叶酸合成酶和脱氢酶）的参与下代谢成二氧化碳，而非灵长类动物则能有效地氧化甲酸盐。人类和猴子的肝脏中 H 4 叶酸和 10-甲酰基 H 4 叶酸脱氢酶水平较低，甲醇中毒后会积累甲酸盐。甲醇代谢和毒性的后果将人和猴子与低等动物区分开来。甲酸很可能是导致人和猴子代谢性酸中毒和眼毒性的原因，而在大多数低等动物中则不会观察到这种情况。然而，具有化学反应活性的甲醛和自由基可能会损伤所有动物物种的细胞的大多数成分，主要是蛋白质和脂质。细胞成分的修饰会导致其功能发生变化。甲醇中毒会降低抗氧化酶和非酶参数的活性和浓度，导致细胞膜磷脂过氧化增强。甲醛和自由基对蛋白质结构的修饰会导致其功能发生变化，特别是对蛋白水解酶及其抑制剂的活性产生影响，从而导致蛋白水解-抗蛋白水解平衡向蛋白水解方向移动，并增强自由基的生成。这种情况可能会导致破坏性过程，因为在增强的膜脂质过氧化过程中，蛋白水解-抗蛋白水解系统的成分可能会从血液渗透到细胞外空间，从而发生不受控制的蛋白水解。这尤其适用于细胞外基质蛋白。
