The efficient asymmetric synthesis of new chiral γ-chloro-α,β-diamino acid derivatives via highly diastereoselective Mannich-type reactions of N-(diphenylmethylene) glycine esters across a chiral α-chloro-N-p-toluenesulfinylimine was developed. The influence of the base, LDA or LiHMDS, used for the formation of the glycine enolates, was of great importance for the anti-/syn-diastereoselectivity of the ...

The genus Chirostoma (silversides) belongs to the family Atherinopsidae, which contains around 150 species, most of which are marine. However, Mexican silverside (Chirostoma estor) is one of the few representatives of freshwater atherinopsids and is only found in some lakes of the Mexican Central Plateau. However, studies have shown that ...

Dihydroceramide Δ4-desaturase 1 (DES1) catalyzes the last step of the de novo ceramide biosynthesis, which consists of the introduction of a trans Δ4-double bond in the carbon chain of the dihydroceramide. It was previously observed that myristic acid binds DES1 through N-myristoylation. This N-terminal modification significantly increased the activity of ...

Mandelic acid (MA) is generally used as a biological indicator of occupational exposure to styrene, which is classified as a class of hazardous environmental pollutants. It was found to undergo one-directional chiral inversion (S-MA to R-MA) in Wistar and Sprague-Dawley rats in vivo. This study was aimed to explore the ...

OBJECTIVES: Effects of bioactive compounds on expression of genes involved in lipid metabolism and fatty acid composition were investigated in Atlantic salmon (Salmo salar L.) primary hepatocytes. METHODS: Five treatments were investigated: I) genistein 0.005 mM, II) genistein 0.025 mM, III) lipoic acid 0.2 mM, IV) sesamin/episesamin 0.05 mM, V) ...

Steatotic livers are sensitive to ischemic events and associated ATP depletion. Hepatocellular necrosis following these events may result from mitochondrial uncoupling protein-2 (UCP2) expression. To test this hypothesis, we developed a model of in vitro steatosis using primary hepatocytes from wild-type and UCP2 knockout mice, and subjected them to hypoxia/reoxygenation ...

Lipid droplet formation and subsequent steatosis has been reported to contribute to hepatotoxicity and is an adverse effect of many pharmacological agents including the anti-epileptic valproic acid (VPA). In this study, we have developed a simple model system Dictyostelium discoideum to investigate the effects of VPA and related compounds in ...

Dairy cows experience an increased demand for glucose to support milk production. However, negative energy balance is a common condition in peripartum cows. In response, fat mobilization provides non-esterified fatty acids (NEFAs) for oxidation in the liver to generate ATP. To investigate the effects of NEFAs on gluconeogenesis, the expression ...

The purpose of this study was to evaluate the use of high resolution LC/MS together with metabolomics and D4-cholic acid (D4-CA) as a metabolic tracer to measure the metabolism and reconjugation of bile acids (BAs) in vitro and in vivo. Metabolic tracers are very important because allow for the direct ...

ABSTRACT: BACKGROUND: Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of saturated and unsaturated fatty acids (FA) on apoptosis in primary rat hepatocytes. METHODS: The primary rat hepatocytes were treated with palmitic ...

Fatty acid microsomal ω-oxidation involves CYP450 enzymes. Some of them belonging to the CYP4F3 family are mainly expressed in the liver making this organ a major player in energy homeostasis and lipid metabolism. To study this important regulation pathway, we used HepaRG cells which gradually undergo a complete differentiation process. ...

ABSTRACT: AIMS: Lipid accumulation in non-adipose tissues leads to cell dysfunction and apoptosis, a phenomenon known as lipotoxicity. Unsaturated fatty acids may offset the lipotoxicity associated with saturated fatty acids. Stearic acid induced endoplasmic reticulum (ER) stress and caused apoptotic and necrotic cell death in the primary rat hepatocytes. METHODS: ...

Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous synthesis of the saturated long-chain fatty acid palmitate. In contrast to most normal cells, FASN is overexpressed in a variety of human cancers including cutaneous melanoma, in which its levels of expression are associated with a poor prognosis ...

Nonalcoholic fatty liver disease (NAFLD) is a known outcome of hepatosteatosis. Free fatty acids (FFA) induce the unfolded protein response (UPR) or endoplasmic reticulum (ER) stress that may induce apoptosis. Recent data indicate ER stress to be a major player in the progression of fatty liver to more aggressive lesions. ...

The effect of polyphenols, phenolic acids and tannins (PPTs) from strawberry and apple on uptake and apical to basolateral transport of glucose was investigated using Caco-2 intestinal cell monolayers. Substantial inhibition on both uptake and transport was observed by extracts from both strawberry and apple. Using sodium-containing (glucose transporters SGLT1 ...

Abstract The osteoclast initiates resorption by creating a resorption lacuna. The ruffled border surrounding the lacunae arises from exocytosis of lysosomes. To dissolve the inorganic phase of the bone, the vacuolar adenosine triphosphatase, located in the ruffled border, pumps protons into the resorption lacunae. The electroneutrality of the lacunae is ...

Collecting duct intercalated cells respond to short-term acid/base perturbations by rapidly shuttling H(+)-ATPase to and from the plasma membrane. Purkerson et al. provide information on the regulation of the anion transporters during chronic acidosis and acute recovery (alkalosis). They found that the major mechanism for both acute and chronic states ...

Phospholipase A(2) releases the fatty acid arachidonic acid from membrane phospholipids. We used the purported phospholipase A(2) stimulator, melittin, to examine the effects of endogenous arachidonic acid signaling on dopamine transporter function and trafficking. In HEK-293 cells stably transfected with the dopamine transporter, melittin reduced uptake of [((3))H]dopamine. Additionally, measurements ...

Endocytosis of nutrient transporters is stimulated under various conditions, such as elevated nutrient availability. In Saccharomyces cerevisiae, endocytosis is triggered by ubiquitination of transporters catalyzed by the E3 ubiquitin ligase Rsp5. However, how the ubiquitination is accelerated under certain conditions remains obscure. Here we demonstrate that closely related proteins Aly2/Art3 ...

Present work on indole-3-acetic acid (IAA)-induced adventitious rooting in sunflower hypocotyl highlights a clear demarcation of nitric oxide (NO)-dependent and NO-independent roles of auxin in this developmental process. Of the three phases of adventitious rooting, induction is strictly auxin-dependent though initiation and extension are regulated by an interaction of IAA ...

An oxalate-fermenting brown rot fungus, Fomitopsis palustris, secretes large amounts of oxalic acid during wood decay. Secretion of oxalic acid is indispensable for the degradation of wood cell walls, but almost nothing is known about the transport mechanism by which oxalic acid is secreted from F. palustris hyphal cells. We ...

BACKGROUND AND PURPOSE The intestinal proton-coupled amino acid transporter, SLC36A1, transports zwitterionic α-amino acids and drugs such as vigabatrin, gaboxadol and δ-aminolevulinic acid. We hypothesize that SLC36A1 might also transport some dipeptides. The aim of the present study was to investigate SLC36A1-mediated transport of Gly-Gly and Gly-Gly mimetics, and to ...

The intraerythrocytic malaria parasite, Plasmodium falciparum, derives amino acids from the digestion of host cell haemoglobin. However, it also takes up amino acids from the extracellular medium. Isoleucine is absent from adult human haemoglobin and an exogenous source of isoleucine is essential for parasite growth. An extracellular source of methionine ...

Medium-chain fatty acids (octanoic and decanoic acids) are well known as fermentation inhibitors. During must fermentation, the toxicity of these fatty acids is enhanced by ethanol and low pH, which favors their entrance in the cell, resulting in a decrease of internal pH. We present here the characterization of the ...

The membrane proteins of the plant preprotein and amino acid transporter (PRAT) superfamily all share common structural elements, such as four membrane-spanning alpha-helices. Interestingly they display diverse localisation to outer and inner membranes of chloroplasts and mitochondria. Furthermore, they fulfil different functions in preprotein translocation as well as amino acid ...

Amino acid supplementation has been shown to enhance the liver-specific functions of cultured hepatocytes during plasma exposure. However, their transport through the cell membrane may restrict their availability for hepatic metabolism. Here, we focus on transport constraints related to uptake of the neutral amino acids and their impact on hepatic ...

Herein we report the synthesis and characterization of a transporter 9 for N-acetylated amino acids. Transporter 9 is a conjugate of a guanidiniocarbonyl pyrrole cation, one of the most efficient carboxylate binding motifs reported so far, and a hydrophobic tris(dodecylbenzyl) group, which ensures solubility in organic solvents. In its protonated ...

The H(+)-coupled amino acid transporter PAT2 (SLC36A2) transports the amino acids proline, glycine, alanine and hydroxyproline. A physiological role played by PAT2 in amino acid reabsorption in the renal proximal tubule is demonstrated by mutations in SLC36A2 that lead to an iminoglycinuric phenotype (imino acid and glycine uria) in humans. ...

The myriad functions of lipids as signalling molecules is one of the most interesting fields in contemporary pharmacology, with a host of compounds recognized as mediators of communication within and between cells. The N-acyl conjugates of amino acids and neurotransmitters (NAANs) have recently come to prominence because of their potential ...

High expression of the system L amino acid transporter has been observed in clinically important tissues including tumors and the blood-brain barrier. We examined amino acid transport system L selectivity of (14)C(U)-L-tyrosine ((14)C-Tyr), (125)I-4-iodo-L-meta-tyrosine (4-(125)I-mTyr), (125)I-6-iodo-L-meta-tyrosine (6-(125)I-mTyr), (125)I-3-iodo-α-methyl-L-tyrosine ((125)I-IMT) and (125)I-3-iodo-L-tyrosine (3-(125)I-Tyr) using Chinese hamster ovary cells (CHO-K1). Cells in ...

HYPOTHESIS AND STUDY OBJECTIVES: We hypothesized that maternal obesity is associated with increased placental amino acid transport and hyperleptinemia. Our objectives were to study placental amino acid transport and the effect of leptin on placental amino acid transport in vitro in the setting of maternal obesity. Seven lean, BMI at ...

Angiotensin-converting enzyme (ACE) 2 is a homolog to the carboxypeptidase ACE, which generates angiotensin II, the main active peptide of renin-angiotensin system (RAS). After the cloning of ACE2 in 2000, three major ACE2 functions have been described so far. First ACE2 has emerged as a potent negative regulator of the ...

Cystinuria is a primary inherited aminoaciduria caused by mutations in the genes that encode the two subunits (neutral and basic amino acid transport protein rBAT and b(0,+)-type amino acid transporter 1) of the amino acid transport system b(0,+). This autosomal recessive disorder (in which few cases show dominant inheritance) causes ...

The nutritional and physiological roles of amino acid (AA)s have been investigated for individual organs. In the current study, we focused on the dynamics of glutamate and transport systems in the pancreas. We employed original procedures to obtain rat pancreatic juice (PJ) subjected to intravenous administration of alanyl-glutamine (AG) for ...

Differential distribution of the plant hormone auxin within tissues mediates a variety of developmental processes. Cellular auxin levels are determined by metabolic processes including synthesis, degradation, and (de)conjugation, as well as by auxin transport across the plasma membrane. Whereas transport of free auxins such as naturally occurring indole-3-acetic acid (IAA) ...

The phosphoinositide3-kinase (PI3K)/Akt and downstream mammalian target of rapamycin complex 1 (mTORC1) signalling cascades promote normal growth and are frequently hyperactivated in tumour cells. mTORC1 is also regulated by local nutrients, particularly amino acids, but the mechanisms involved are poorly understood. Unexpectedly, members of the proton-assisted amino-acid transporter (PAT or ...

Fatty acid oxidation is highly regulated in skeletal muscle and involves several sites of regulation, including the transport of fatty acids across both the plasma and mitochondrial membranes. Transport across these membranes is recognized to be primarily protein mediated, limited by the abundance of fatty acid transport proteins on the ...

Dietary long-chain fatty acid (LCFA) uptake across cell membranes is mediated principally by fatty acid transport proteins (FATPs). Six subtypes of this transporter are differentially expressed throughout the human and rodent body. To facilitate drugs discovery against FATP subtypes, the authors used mammalian cell lines stably expressing the recombinant human ...

Previous studies on glutamate (GLU) and its receptors in the pond snail Lymnaea stagnalis have suggested that GLU functions as a neurotransmitter in various behaviors, particularly for generation of feeding rhythm. The uptake mechanism of GLU is not yet known in Lymnaea. In the present study, we characterized the GLU ...

Regiospecific and conformationally restrained analogs of melphalan and DL-2-NAM-7 have been synthesized and their affinities for the large neutral amino acid transporter (LAT1) of the blood-brain barrier have been determined to assess their potential for accessing the CNS via facilitated transport. Several analogs had K(i) values in the range 2.1-8.5 ...

Amino acid transfer from mother to fetus via the placenta plays a critical role in normal development, and restricted transfer is associated with fetal growth restriction. Placental amino acid transfer involves the interaction of 15 or more transporters and 20 amino acids. This complexity means that knowing which transporters are ...

Several health-beneficial properties of hop bitter acids have been reported (inhibition of bone resorption and anticarcinogenic and anti-inflammatory activities); however, scientific data on the bioavailability of these compounds are lacking. As a first approach to study the bioavailability, the epithelial transport of hop alpha- and beta-acids across Caco-2 monolayers was ...

The reduced expression of the bile salt export pump (BSEP/ABCB11) at the canalicular membrane is associated with cholestasis-induced hepatotoxicity due to the accumulation of bile acids in hepatocytes. We previously reported that 4-phenylbutyrate (4PBA), an approved drug for urea cycle disorders, is a promising agent for intrahepatic cholestasis because it ...

Glucose, fatty acids, and L-carnitine are important substrates that support mammary epithelial cell metabolism, biosynthetic capacity, and milk yield and composition. Our study investigated the effects of LPS-induced inflammation on the expression of several glucose, fatty acid, and L-carnitine transporters in the lactating rat mammary gland at different lactation stages. ...

In addition to their classical roles as carbon or nitrogen sources, amino acids can be used for bacterial virulence, colonization, or stress resistance. We found that original deamidase-transport systems impact colonization by Helicobacter pylori, a human pathogen associated with gastric pathologies, including adenocarcinoma. We demonstrated that l-asparaginase (Hp-AnsB) and gamma-glutamyltranspeptidase ...

Cynomorium songaricum Rupr. (SY) is a central nervous system-oriented herb material that has actions of anti-dementia, anti-epilepsy, and anti-stress. It is unclear whether SY would be biologically active in functionally regulating neurotransmitter transporters. Here, we assessed these potential actions using Chinese hamster ovary cells expressing gamma-aminobutyric acid (GABA) transporter (GAT-1), ...

Intracerebral accumulation of neurotoxic dicarboxylic acids (DCAs) plays an important pathophysiological role in glutaric aciduria type I and methylmalonic aciduria. Therefore, we investigated the transport characteristics of accumulating DCAs - glutaric (GA), 3-hydroxyglutaric (3-OH-GA) and methylmalonic acid (MMA) - across porcine brain capillary endothelial cells (pBCEC) and human choroid plexus ...

The results presented here show that STC-1 cells, a model of intestinal endocrine cells, respond to a broad range of amino acids, including l-proline, l-serine, l-alanine, l-methionine, l-glycine, l-histidine, and alpha-methyl-amino-isobutyric acid (MeAIB) with a rapid increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)). We sought to identify the mechanism by ...

Transport of long-chain fatty acids across the cell membrane has long been thought to occur by passive diffusion. However, in recent years there has been a fundamental shift in understanding, and it is now generally recognized that fatty acids cross the cell membrane via a protein-mediated mechanism. Membrane-associated fatty acid-binding ...

Amino acids are the currency of nitrogen exchange between source and sink tissues in plants and constitute a major source of the components used for cellular growth and differentiation. The characterization of a new amino acid transporter belonging to the amino acid permease (AAP) family, AAP11, expressed in the perennial ...