CARBOHYDRATE AND LIPID METABOLIC PATHWAYS

碳水化合物和脂质代谢途径

• 批准号: 3483067
• 负责人: BERNARD R LANDAU
• 金额: $ 35.08万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3483067
• 关键词: Krebs' cycle; NAD(H) phosphate; NAD(P)H dehydrogenase; acetaminophen; acetone; acetyl coA; alpha ketoglutarate; carbohydrate metabolism; carbon; cholesterol; diabetes mellitus; fructose; galactose; glucagon; gluconeogenesis; glucose 6 phosphatase; glucuronides; glutamine; glycolysis; high performance liquid chromatography; human subject; laboratory rat; lipid metabolism; liver metabolism; mannose; noninsulin dependent diabetes mellitus; oxidation; perfusion; phenylacetates; radionuclides; radiotracer; steroid biosynthesis; tritium

Methods are to be developed and applied for quantitating pathways in physiological and pathological states with three specific aims. First, methods are to be developed for noninvasively sampling in humans intermediates of carbohydrate metabolism: a) The use of 13C rather than 14C to sample hepatic glucose-6-P with acetaminophen glucuronide will be examined and whether the glucuronide sample a single pool of hepatic glucose- 6-P and UDP-glucose will be further assessed by (1) administering various labeled substrates to normal subjects and comparing 14C distributions in glucuronide and blood glucose and (2) comparing distributions in glucuronide and glycogen from rats given 14C glucose and acetaminophen; b) Phenylacetate will be given to normals with 14C substrates to see if its urinary glutamine conjugate reflects hepatic alpha-ketoglutarate; c) Similary, it will be determine if the glycine conjugate of benzoic acid reflects hepatic 3-phosphoglyceric acid. Second, in part using these probes where applicable: a) The extent of futile cycling in normals, type II diabetics and thyrotoxics will be estimated correcting for (1) the extent of retention of 3H from (2- 3h)glucose-6-P, (2) the detritiation of (3-3H)glucose in the pentose cycle and (3) the retention of 3H of (6-3H)glucose in Cori cycling; b) The extent of isotopic equilibration of hepatic glucose-6-P with fructose-6-P and the pentose-5-P's will be estimated and the data applied to a model for quantitating pentose cycle activity in liver; c) The contribution of the indirect pathway in the fed state will be estimated from randomization of 14C from (6-14C)glucose, the site of the pathway assessed from comparisons of randomizations from 14C galactose, mannose, and the phenylacetate probe used to estimate 12C dilution of 14C in the Krebs cycle; d) If possible, the phenylacetate probe will also be to quantitate the pathways of acetaone metabolism. Third, by specifically labeling the acetyl CoA formed in the cellular evnironment of omega-oxidation and the peroxisomes and of NADPH formed in the endoplasmic reticulum in the rat, determine if there are specific pools of acetyl and NADPH used for cholesterol synthesis in liver.

将开发和应用方法， 在生理和病理状态下， 明确的目标。 首先，要制定方法， 人体碳水化合物中间体的非侵入性采样 代谢：a）使用13 C而不是14 C来对肝脏进行采样 将检查葡萄糖-6-P和对乙酰氨基酚葡萄糖醛酸苷， 葡萄糖醛酸苷样本是否为单一肝葡萄糖池- 6-P和UDP-葡萄糖将通过（1）施用 各种标记底物与正常受试者比较， 葡萄糖醛酸苷和血糖的分布，以及（2）比较 给予14 C的大鼠中葡糖苷酸和糖原的分布 葡萄糖和对乙酰氨基酚; B）给予苯乙酸酯， 正常人与14 C底物，看看它的尿谷氨酰胺 缀合物反映肝α-酮戊二酸; c）类似地，其将 确定苯甲酸的甘氨酸共轭物是否反映 肝3-磷酸甘油酸。 第二，部分利用这些 a）在适用的情况下， 将估计正常人、II型糖尿病患者和甲状腺毒性患者 校正（1）从（2- 3 h）葡萄糖-6-P;（2）戊糖中（3- 3 H）葡萄糖的还原 （3）（6- 3 H）葡萄糖在科里循环中的3 H保留; B）肝葡萄糖-6-P与 果糖-6-P和戊糖-5-P的估计和数据 应用于定量肝脏戊糖循环活性的模型; c）进食状态下间接途径的贡献将 通过从（6- 14 C）葡萄糖中随机分配14 C来估计， 根据随机化比较评估的途径部位 从14 C半乳糖、甘露糖和所用的苯乙酸探针 估计克雷布斯循环中14 C的12 C稀释; d）如果可能， 苯乙酸探针也将定量 丙酮代谢 第三，通过特异性标记乙酰基， 辅酶A形成于细胞内的氧化反应， 过氧化物酶体和NADPH在内质中形成 大鼠的网状细胞，确定是否有特定的网状细胞库 乙酰和NADPH用于肝脏中胆固醇的合成。