Abstract:
:Carnitine acyltransferases catalyze the exchange of acyl groups between carnitine and coenzyme A (CoA). These enzymes include carnitine acetyltransferase (CrAT), carnitine octanoyltransferase (CrOT), and carnitine palmitoyltransferases (CPTs). CPT-I and CPT-II are crucial for the beta-oxidation of long-chain fatty acids in the mitochondria by enabling their transport across the mitochondrial membrane. The activity of CPT-I is inhibited by malonyl-CoA, a crucial regulatory mechanism for fatty acid oxidation. Mutation or dysregulation of the CPT enzymes has been linked to many serious, even fatal human diseases, and these enzymes are promising targets for the development of therapeutic agents against type 2 diabetes and obesity. We have determined the crystal structures of murine CrAT, alone and in complex with its substrate carnitine or CoA. The structure contains two domains. Surprisingly, these two domains share the same backbone fold, which is also similar to that of chloramphenicol acetyltransferase and dihydrolipoyl transacetylase. The active site is located at the interface between the two domains, in a tunnel that extends through the center of the enzyme. Carnitine and CoA are bound in this tunnel, on opposite sides of the catalytic His343 residue. The structural information provides a molecular basis for understanding the catalysis by carnitine acyltransferases and for designing their inhibitors. In addition, our structural information suggests that the substrate carnitine may assist the catalysis by stabilizing the oxyanion in the reaction intermediate.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Jogl G,Hsiao YS,Tong Ldoi
10.1196/annals.1320.002subject
Has Abstractpub_date
2004-11-01 00:00:00pages
17-29eissn
0077-8923issn
1749-6632pii
1033/1/17journal_volume
1033pub_type
杂志文章,评审abstract::Cotyledons of dark-grown watermelon seedlings contain during the first period of germination, 4 and later 5 MDH isoenzymes. Whereas isoenzymes I, II, and IV belong to the cytosol, isoenzyme III is confined to the mitochondria (mMDH) and isoenzyme V to the glyoxysomes (gMDH). The organelle-bound MDHs were purified to h...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1982.tb21427.x
更新日期:1982-01-01 00:00:00
abstract::We report a case of latent autoimmune diabetes in adults (LADA), also known as slowly progressive type 1 diabetes (SPT1D), followed up for changes, including reactivity to the GAD65 antibody epitope for the 9-year period from impaired glucose tolerance (IGT) to the insulin-dependent stage (IDDM). This 69-year-old male...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1447.022
更新日期:2008-12-01 00:00:00
abstract::Various biological activities of peptides have been found. In this study, the induction of apoptosis in a human lymphoma cell line (U937) by peptide fraction separated from anchovy sauce was studied using biochemical and flow cytometric methods. After U937 was treated with a hydrophobic peptide fraction of the anchovy...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1299.073
更新日期:2003-12-01 00:00:00
abstract::We have shown that drinking red wine reduces oxidation of LDL. This reduction in oxidation has been attributed to the polyphenolic compounds in red wine, but the mechanisms of absorption and metabolism of these compounds has been unclear. We therefore investigated the absorption and metabolism of polyphenols using rat...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2002.tb02934.x
更新日期:2002-05-01 00:00:00
abstract::Osteocytes are derived from osteoblasts and make up over 90% of the cells in bone. However, the mechanisms that control the differentiation of osteoblasts into osteocytes embedded in bone matrix are not well understood. With the recent developments of transgenic models for manipulating gene expression in osteocytes an...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2009.05246.x
更新日期:2010-03-01 00:00:00
abstract::Both orbital and attitude dynamics employ the method of variation of parameters. In a non-perturbed setting, the coordinates (or the Euler angles) are expressed as functions of the time and six adjustable constants called elements. Under disturbance, each such expression becomes ansatz, the "constants" being endowed w...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1370.016
更新日期:2005-12-01 00:00:00
abstract::Lipogenesis occurs primarily in the liver, where dietary carbohydrates control the expression of key enzymes in glycolytic and lipogenic pathways. We have recently discovered that the transcription factor XBP1, best known as a key regulator of the unfolded protein response (UPR), is required for de novo fatty acid syn...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2009.04956.x
更新日期:2009-09-01 00:00:00
abstract::The receptor that mediates the specific uptake and intracellular transport of dimeric immunoglobulin A (IgA dimer) in mucosal and glandular epithelia is identical with a transmembrane precursor of secreted secretory component. During transport, the IgA dimer receptor (membrane SC) is cleaved into two domains, a membra...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1983.tb26914.x
更新日期:1983-06-30 00:00:00
abstract::Auditory brainstem potentials were recorded from various scalp and nasopharyngeal sites referenced both to a noncephalic site and to certain scalp locations in normal humans. The distribution of amplitudes and latencies of the components were defined. There were significant amplitude, polarity, and latency asymmetries...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1982.tb50807.x
更新日期:1982-01-01 00:00:00
abstract::A remarkable "steroid sparing" effect of Saiboku-to was noted within 6 to 12 months of treatment in steroid-dependent asthmatic patients. Saiboku-to spared the downregulation of glucocorticoid receptor of human lymphocytes, plasma ACTH, and cortisol levels. It also spared downregulation of beta 2 receptor by beta 2 ag...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1993.tb35918.x
更新日期:1993-06-23 00:00:00
abstract::Reports on patients with hemiparalysis indicate the importance of the nervous system for the pathophysiology of rheumatoid arthritis (RA) or osteoarthritis (OA). Norepinephrine (NE) and opioids seem to be more antiinflammatory neurotransmitters whereas substance P is proinflammatory. The study aimed to investigate the...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1999.tb07649.x
更新日期:1999-06-22 00:00:00
abstract::Nitric oxide (NO) is an important signaling molecule that is generated through the catalytic activity of nitric oxide synthase (NOS). In the brain, NO mediates neuronal survival, synaptic plasticity, vascular smooth muscle relaxation, and endothelial cell permeability. Previous studies demonstrated aberrant expression...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2000.tb06351.x
更新日期:2000-04-01 00:00:00
abstract::This paper presents a review of the publicly available knowledge base concerning turbine blade tip heat transfer, from the early fundamental research which laid the foundations of our knowledge, to current experimental and numerical studies utilizing engine-scaled blade cascades and turbine rigs. Focus is placed on hi...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2001.tb05843.x
更新日期:2001-05-01 00:00:00
abstract::Phagocytes play a major role in several diseases. In particular mononuclear phagocyte-derived foam cells have a prominent role in the development of the atherosclerotic lesions. Macrophages are present in all stages of atherogenesis; they internalize lipoproteins and accumulate cholesterol. Moreover, lipid-filled macr...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.1997.tb46260.x
更新日期:1997-12-15 00:00:00
abstract::To examine whether treatment with cardiopulmonary bypass (CPB), which causes transient cellular immunity depression, influences tuberculin skin testing (TST) interpretation. The study was also aimed to assess the degree of cellular immunity depression following open heart surgery. Fifteen children from developing coun...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1398.027
更新日期:2007-08-01 00:00:00
abstract::Information processing in the rodent hippocampus is fundamentally shaped by internally generated sequences (IGSs), expressed during two different network states: theta sequences, which repeat and reset at the ∼8 Hz theta rhythm associated with active behavior, and punctate sharp wave-ripple (SWR) sequences associated ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13329
更新日期:2017-05-01 00:00:00
abstract::The W-curve is a numerical mapping algorithm that provides tertiary information content of long and short genomic sequences. The most popular genomic pattern recognition algorithms depend on string matching of the primary information content of short genomic sequences. Herein, we describe a way to define the fuzzy pro...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2002.tb04887.x
更新日期:2002-12-01 00:00:00
abstract::Tick-borne pathogens in the genus Ehrlichia cause emerging zoonoses. Although laboratory mice are susceptible to Ehrlichia infections, many isolates do not cause clinical illness. In contrast, the Ixodes ovatus Ehrlichia-like agent (IOE) causes disease and immune responses in mice comparable to the human illness cause...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04520.x
更新日期:2009-05-01 00:00:00
abstract::The Guillain Barré syndromes (GBS) are the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the pathophysiological events of GBS, and improving immunotherapies are fundamental to improving the clinical outcome. Recent research into GBS and the Miller Fisher syndrome (MFS) variant has fo...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1405.010
更新日期:2008-01-01 00:00:00
abstract::About 1 of 10 women, particularly those older than 60 years of age, shows some degree of thyroid hormone deficiency. Thyroid diseases are generally characterized by perturbations of thyroid signaling homeostasis. The most common examples of thyroid diseases include hypothyroidism, hyperthyroidism, and several types of...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.13980
更新日期:2019-05-01 00:00:00
abstract::The essential trace element selenium is of fundamental importance to human biology. Information on the membrane-bound selenoproteins was obtained by labeling of rats in vivo with (75)Se-selenite, subcellular fractionation of the tissue homogenates, separation of the proteins by SDS-PAGE, two-dimensional electrophoresi...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2002.tb04652.x
更新日期:2002-11-01 00:00:00
abstract::Sensorineural hearing loss results from the degeneration of hair cells and/or auditory neurons in the cochlea of the inner ear. BDNF and NT-3 were shown to support survival of auditory neurons both in vitro and in vivo. Cochlea from P3-P4 rats were cultured as floating explants and hair cells in the organ of Corti wer...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1999.tb08648.x
更新日期:1999-11-28 00:00:00
abstract::The human spatial orientation system is highly complex and nonlinear. It is difficult, therefore, to arrive at an unequivocal model of the underlying processing by merely combining the known elementary mechanisms ("bottom-up" approach); additional "top-down" concepts are required to narrow the choice between several f...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1303.028
更新日期:2003-10-01 00:00:00
abstract::Many features of these gastric vesicles satisfy the requirements for the gastric H+ pump. For example, we have: (a) K+ requirement, (b) KA for K+ of about 30 mM; (c) identical cation sequence for tissue and vesicles, (d) similar anion sequence, (e) localization at the microvillus of the secretory canaliculus, (f) TI+ ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.1980.tb47181.x
更新日期:1980-01-01 00:00:00
abstract::Myasthenia gravis (MG) is usually caused by autoantibodies against muscle nicotinic acetylcholine receptor (AChR), which is composed of five subunits (alpha(2)betagammadelta or alpha(2)betaepsilondelta). Current treatments, including plasmapheresis, are nonspecific, causing several side effects. We aim to develop an a...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1405.017
更新日期:2008-01-01 00:00:00
abstract::Oral and nasal administration of nicotinic acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with AChR and complete Freund's adjuvant (CFA) resulted in prevention or marked decrease of the severity of experimental autoimmune myasthenia gravis (EAMG) and suppression of AChR-specific B-cel...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1996.tb21135.x
更新日期:1996-02-13 00:00:00
abstract::Metastasis is the main cause of human cancer deaths, and cell motility is one key component of the process of metastasis. The ERK mitogen-activated protein kinase (MAPK) signaling pathway is probably one of the most commonly activated in malignant human cancers. We describe the molecular mechanisms by which ERK MAPK s...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1329.027
更新日期:2004-12-01 00:00:00
abstract::The aim of this retrospective study is to assess the frequency of HLA-B27 and HLA-B51 in healthy subjects from the center of Tunisia and to investigate their usefulness in the diagnosis of ankylosing spondylitis (AS) and Behçet's disease (BD), respectively. Microlymphocytotoxicity test was used to perform serologic HL...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04756.x
更新日期:2009-09-01 00:00:00
abstract::Several recently published reports, including ours, suggest that adiponectin is a strong proinflammatory agent. Indeed, exposure of human placenta and adipose tissue to adiponectin induces the production of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2). We hav...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1367.013
更新日期:2006-11-01 00:00:00
abstract::Cognitive training, physical activity, and exercise have often been reported to improve cognitive performance in older adults. This paper reviews some seminal and recent studies using these approaches to improve cognition and physical functioning in healthy older adults and in patients suffering from non-neurological ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.12682
更新日期:2015-03-01 00:00:00