Aspects of Biotin Nutrition

生物素营养的各个方面

基本信息

批准号：
8019468
负责人：
Donald M Mock
金额：
$ 36.82万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8019468
关键词：
Acetyl-CoA Carboxylase Adult Affect Affinity Chromatography Alkaline Phosphatase Amino Acid Sequence Antibodies Anticonvulsants Arachidonic Acids Arkansas Avidin Biological Assay Biotin Biotinylation CD-I Case-Control Studies Catabolism Cell Count Cell Culture Techniques Cell Line Cell membrane Cells Cities Cleft Palate Clinical Research Custom Cyclooxygenase Inhibitors Data Defect Development Diet Monitoring Dinoprostone Drops Egg White Enzymes Erythrocytes Eukaryotic Cell Excretory function Experimental Designs Face Fatty Acids Fetal Movement Fetal Skeleton Fetus Gel Gene Chips Gene Expression Genes Genetic Goals Harvest Histones Human Individual Infant Inpatients Instruction Insulin Laboratories Leucine Limb Bud Limb structure Literature Lymphocyte MCT-1 gene Malonyl Coenzyme A Measures Medical Methods Modification Molecular Mus Mutation Names Nature Osteogenesis Palate Pathway interactions Peptide Sequence Determination Plasma Ploidies Pregnancy Principal Investigator Printing Procedures Production Progress Reports Prostaglandins Proteins Proteomics Research Research Personnel Research Project Grants Reverse Transcriptase Polymerase Chain Reaction Role Sampling Science Screening procedure Small Interfering RNA Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Staining method Stains Supplementation Testing Time TimeLine Tissues Umbilical Cord Blood Universities Veterans Hospitals biotin transporter bisnorbiotin blood glucose regulation design feeding fetal improved in vivo interest intravenous glucose tolerance test malformation methylmalonyl-CoA decarboxylase monomer mouse model nutrition oxidation programs protein aminoacid sequence response sample collection scale up urinary

项目摘要

Long term goals of this project are to determine the biotin requirements for normal individuals and for individuals in circumstances in which biotin status may be impaired and to investigate the consequences and pathogenic mechanisms of marginal biotin deficiency.We recently demonstrated that marginal biotin deficiency is common during normal human gestation and have demonstrated that marginal deficiency is quite teratogenic in mice. Thus, the following five specific aims are relevant and timely. In Specific Aim #1, we will test the hypothesis that maternal biotin deficiency causes abnormal development of fetal skeleton and palate by causing deficient fetal activity of the biotin-dependent enzyme acetyl-CoA carboxylase which leads in turn to deficiency of arachidonic acid and prostaglandin. In fetal palate and limb bud explants from biotin deficient and sufficient CD-I mice, we will quantitate fetal arachidonic acid content and synthesis rates and will examine the malformation ameliorating effects of supplementation of arachidonic acid and prostaglandin and the amelioration blocking effects of cyclooxygenase inhibitors. Analogous studies will also be conducted in vivo; In Specific Aim #2, we will test the hypothesis that infants with cleft palate or limb shortening have significantly reduced biotin status compared to normal infants. In a case-controlled study, biotin status will be assessed in cord blood using odd-chain fatty acid composition in red blood cell membranes and plasma and lymphocyte activity of the biotin-dependent enzyme propionyl-CoA carboxylase. In Specific Aim #3, we will clone and sequence a biotin transporter recently discovered in our laboratory. In studies of cells from the first individual with biotin transporter deficiency, we will investigate the molecular nature of the genetic defect. In Specific Aim #4, we will confirm promising new indicators of biotin status and investigate the validity of the expression of particular biotin-related genes (e.g., carboxylases) as indicators of marginal biotin deficiency in healthy adults rendered marginallybiotin deficiency by egg-white feeding. In Specific Aim #5, we will determine the subcellular localization of the enzyme(s) responsible for catalyzing the p-oxidation of biotin to the inactive metabolite bisnorbiotin and characterize this pathway. Understanding of this pathway is important because accelerated biotin catabolism may be the major cause of biotin deficiency in pregnancy and anticonvulsants. PERFORMANCE snt(S) (organization, city, state) University of Arkansas for Medical Sciences, Little Rock, AR General Clinical Research Center, McClellan Veteran's Hospital, Little Rock, AR KEY PERSONNEL. See instructions on Page 11. Use continuation pages as needed to provide the required information in the format shown below. Name Organization Role on Project Donald M. Mock Univ. Arkansas for Medical Sciences Principal investigator PHS398 (Rev. 4/98) Page 2 BB cc Princip tigator/Program Director (Last, first, middle): MOC snald M. Type the rams of the principal investigator/pn 'director at the top of each printed page and each Onuafon page. (For type specifications, see instructions on page 6.) RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description,

该项目的长期目标是确定普通人和在生物素地位可能受到损害并调查后果的情况下边际生物素缺乏症的致病机制。我们最近证明了边际生物素缺乏症是在正常的人妊娠期间常见，并证明边缘缺乏在老鼠。因此，以下五个特定目标是相关且及时的。在特定的目标＃1中，我们将检验以下假设，即母体生物素缺乏会导致异常发育胎儿骨骼和味蕾通过引起生物素依赖性酶乙酰辅酶A羧化酶的胎儿活性不足这又导致了蛛网膜酸和前列腺素的缺乏。在胎儿和肢体芽外植体中生物素缺乏和足够的CD-I小鼠，我们将定量胎儿花生四烯酸含量和合成速率，以及将检查畸形可以改善补充花生四烯酸和前列腺素以及环氧酶抑制剂的改善阻断作用。类似研究也将在体内进行；在特定的目标＃2中，我们将测试以下假设，即a裂或肢体缩短的婴儿明显与正常婴儿相比，生物素状态降低。在一项病例控制的研究中，生物素状态将在绳索中进行评估在红细胞膜中使用奇链脂肪酸组成的血液，血浆和血浆和淋巴细胞活性依赖生物素的酶丙酰辅酶A羧化酶。在特定的目标＃3中，我们将克隆并对生物素进行序列运输者最近在我们的实验室中发现。在生物素转运蛋白第一个个体的细胞研究中缺乏症，我们将研究遗传缺陷的分子性质。在特定的目标＃4中，我们将确认有希望的生物素状态的新指标，并研究了特定生物素相关的表达的有效性基因（例如羧化酶）作为健康成年人边际生物素缺乏症的指标卵白色喂养不足。在特定的目标＃5中，我们将确定酶负责催化生物素的P-氧化为无活性代谢物双诺比蛋白和表征此途径。对这一途径的理解很重要，因为加速的生物素分解代谢可能成为妊娠和抗惊厥药中生物素缺乏症的主要原因。绩效SNT（S）（组织，城市，州）阿肯色大学医学科学大学，小石城，AR AR小石城麦克莱伦资深医院一般临床研究中心关键人员。请参阅第11页的说明。根据需要使用延续页面，以下面显示的格式提供所需的信息。姓名组织角色唐纳德·M·莫克大学。阿肯色州医学科学首席研究员 PHS398（修订版4/98）第2页BB CC主管/程序总监（最后，第一，中间）：MOC Snald M. 在每个印刷页面的顶部和每个Onuafon页面的顶部输入主要调查员/PN董事的公羊。（对于类型规格，请参阅第6页的说明）。研究赠款目录页码面部第1页描述，

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biotin accounts for less than half of all biotin and biotin metabolites in the cerebrospinal fluid of children.

生物素占儿童脑脊液中所有生物素和生物素代谢物的不到一半。

DOI：
10.3945/ajcn.2008.26525
发表时间：
2008
期刊：
The American journal of clinical nutrition
影响因子：
0
作者：
Bogusiewicz,Anna;Stratton,ShawnaL;Ellison,DaleA;Mock,DonaldM
通讯作者：
Mock,DonaldM

In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

DOI：
10.3945/jn.114.201343
发表时间：
2015
期刊：
The Journal of nutrition
影响因子：
0
作者：
A. Bogusiewicz;G. Boysen;D. Mock
通讯作者：
A. Bogusiewicz;G. Boysen;D. Mock

Quantitative measurement of urinary excretion of 3-hydroxyisovaleryl carnitine by LC-MS/MS as an indicator of biotin status in humans.

DOI：
10.1021/ac102330k
发表时间：
2010-11-15
期刊：
ANALYTICAL CHEMISTRY
影响因子：
7.4
作者：
Horvath, Thomas D.;Stratton, Shawna L.;Bogusiewicz, Anna;Owen, Suzanne N.;Mock, Donald M.;Moran, Jeffery H.
通讯作者：
Moran, Jeffery H.

Adequate intake of biotin in pregnancy: why bother?

怀孕期间摄入足够的生物素：何必那么麻烦呢？

DOI：
10.3945/jn.114.203356
发表时间：
2014
期刊：
The Journal of nutrition
影响因子：
0
作者：
Mock,DonaldM
通讯作者：
Mock,DonaldM

Quantitative measurement of plasma 3-hydroxyisovaleryl carnitine by LC-MS/MS as a novel biomarker of biotin status in humans.

DOI：
10.1021/ac1003213
发表时间：
2010-05-15
期刊：
ANALYTICAL CHEMISTRY
影响因子：
7.4
作者：
Horvath, Thomas D.;Stratton, Shawna L.;Bogusiewicz, Anna;Pack, Lindsay;Moran, Jeffery;Mock, Donald M.
通讯作者：
Mock, Donald M.