GLYCEROLIPID METABOLISM IN MICROBODIES

微生物中的甘油脂代谢

• 批准号: 3396458
• 负责人: AMIYA K HAJRA
• 金额: $ 8.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396458
• 关键词: acyl coA; acyltransferase; adrenal glands; brain metabolism; carnitine; catalase; clofibrate; density gradient ultracentrifugation; dietary carbohydrates; dietary lipid; dihydroxyacetone; endoplasmic reticulum; enzyme substrate; fasting; glycerides; gonads; growth /development; kidney; kidney metabolism; lipid biosynthesis; lipogenesis inhibitor; liver metabolism; membrane permeability; nutrition related tag; peroxisome; phosphates; radiotracer; thin layer chromatography; tritium

Peroxisomes and microperoxisomes (microbodies) are ubiquitous catalase-containing subcellular organelles whose function in tissues is as yet unknown. There are a number of indications that these organelles play a role in cellular metabolism of lipids. For example, results from our laboratory have shown that some of the enzymes for glycerolipid biosynthesis are localized in microbodies. In higher animals glycerolipids are synthesized either via glycerophosphate or via acyl dihydroxyacetone phosphate. Acyl dihydroxyacetone phosphate has been also shown to be a requisite precursor of all glycerol ether lipids (alkly glycerol ethers and plasmalogens). We have found that the key enzymes of the acyl dihydroxyacetone phosphate pathway for glycerolipid biosynthesis are localized in the rat, mouse and guinea pig liver peroxisomes. The major objective of this research proposal is to investigate the interrelationship between microbodies and cellular lipid metabolism. We will pursue our hypothesis that peroxisomes are primarily involved in supplying the metabolic intermediates to other cellular compartments for lipid biosynthesis. Methods will be developed for the preparative isolation of peroxisomes from liver and kidney and microperoxisomes from developing brain, adrenal glands and gonads. With the purified preparations of microbodies we will perform extensive studies of their enzyme composition and metabolites content. The distribution of the enzymes in microbodies (e.g. membrane-bound or soluble or present in the core) of different tissues and the topography of the membrane-bound enzymes will be studied. We will continue our studies of the effects of hypolipidemic agents to develop a more detailed picture of the changes which take place in peroxisomal enzymes and metabolic intermediates. These agents, such as clofibrate, are known to cause a proliferation of liver peroxisomes and change the activity of a number of enzymes in liver. In addition, detailed studies will be performed on the effects of other physiological parameters such as fasting, feeding a high fat or high carbohydrate diet and administering hormones (which are known to control lipid metabolism) to animals, on the activity of peroxisomal enzymes. The results of these studies should be useful in delineating the physiological function of microbodies in tissues.

过氧化物酶体和微氧化酶体（微型生物）无处不在 含状酶的亚细胞细胞器，其在组织中的功能为 但未知。 有许多迹象表明这些细胞器会玩 在脂质的细胞代谢中的作用。 例如，我们的结果 实验室表明甘油脂脂的某些酶 生物合成位于微生物中。 在较高的动物中 通过甘油磷酸盐或通过酰基二羟基丙酮合成 磷酸盐。 酰基二羟基丙酮磷酸盐也已被证明是 所有甘油乙醚脂质的必要前体（碱甘油醚和 血浆元）。 我们发现酰基的关键酶 二羟基丙酮磷酸途径用于甘油生物合成是 位于大鼠，小鼠和豚鼠肝过氧化物酶体中。 该研究建议的主要目的是调查 微生物和细胞脂质代谢之间的相互关系。 我们 将提出我们的假设，即过氧化物酶体主要参与 向其他细胞室提供代谢中间体的 脂质生物合成。 将为制备者开发方法 从肝脏，肾脏和微氧化酶体分离出过氧化物酶体从 发展大脑，肾上腺和性腺。 带有纯化 微型生物的制备我们将对它们的广泛研究 酶成分和代谢物含量。 分布 微生物中的酶（例如，膜结合或可溶性或存在于 不同组织的核心）和膜结合酶的地形 将被研究。 我们将继续研究 低脂药物以开发更详细的变化图片 发生在过氧化物酶体酶和代谢中间体中。 这些 已知药物（例如锁骨振动）会引起肝脏的增殖 过氧化物酶体并改变肝脏中许多酶的活性。 在 此外，将对其他其他研究进行详细的研究 生理参数，例如禁食，喂养高脂肪或高脂肪 碳水化合物饮食和施用激素（已知可以控制 对动物的脂质代谢，对过氧化物酶体酶的活性。 这 这些研究的结果应该有用 微型生物在组织中的功能。