Adrenergic receptors and cardiovascular effects of catecholamines.
Motiejunaite Justina,Amar Laurence,Vidal-Petiot Emmanuelle
Annales d'endocrinologie
Activation of the sympathetic nervous system is responsible for the body's "fight or flight" reaction. The physiological responses to the activation of the sympathetic nervous system and adrenal medulla are mediated through the action of the endogenous catecholamines norepinephrine (or noradrenaline) and epinephrine (or adrenaline) on adrenergic receptors. Adrenergic receptors belong to the superfamily of G protein-coupled receptors (GPCR). Adrenoceptors are divided into alpha1, alpha2, beta1, beta2 and beta3 receptors. Norepinephrine stimulates both subtypes of α receptors and β1 receptors. Epinephrine stimulates all subtypes ofα and β adrenoreceptors. α1 adrenergic receptors, coupled to stimulatory Gq proteins, activate the enzyme phospholipase C and are mainly found in the smooth muscle cells of blood vessels and urinary tract, where they induce constriction. α2 receptors are coupled to inhibitory Gi proteins, that inactivate adenylyl cyclase, decreasing cyclic adenosine monophosphate (AMP) production. They are mainly found in the central nervous system, where their activation results in a decreased arterial blood pressure. β1 adrenoreceptors predominate in the heart, activate the Gs-adenylyl cyclase -cAMP-protein kinase A signaling cascade, and induce positive inotropic and chronotropic effects. β2 adrenoreceptors are distributed extensively throughout the body, but are expressed predominantly in bronchial smooth muscle cells. β2 adrenergic receptors activate adenylyl cyclase, dilate blood vessels and bronchioles, relax the muscles of the uterus, bladder and gastrointestinal duct, and also decrease platelet aggregation and glycogenolysis. β3 receptors can couple interchangeably to both stimulating and inhibiting G proteins. They are abundantly expressed in white and brown adipose tissue, and increase fat oxidation, energy expenditure and insulin-mediated glucose uptake. This review details the regulation of cardiac and vascular function by adrenergic receptors.
10.1016/j.ando.2020.03.012
Amino Acids in Intestinal Physiology and Health.
Beaumont Martin,Blachier François
Advances in experimental medicine and biology
Dietary protein digestion is an efficient process resulting in the absorption of amino acids by epithelial cells, mainly in the jejunum. Some amino acids are extensively metabolized in enterocytes supporting their high energy demand and/or production of bioactive metabolites such as glutathione or nitric oxide. In contrast, other amino acids are mainly used as building blocks for the intense protein synthesis associated with the rapid epithelium renewal and mucin production. Several amino acids have been shown to support the intestinal barrier function and the intestinal endocrine function. In addition, amino acids are metabolized by the gut microbiota that use them for their own protein synthesis and in catabolic pathways releasing in the intestinal lumen numerous metabolites such as ammonia, hydrogen sulfide, branched-chain amino acids, polyamines, phenolic and indolic compounds. Some of them (e.g. hydrogen sulfide) disrupts epithelial energy metabolism and may participate in mucosal inflammation when present in excess, while others (e.g. indole derivatives) prevent gut barrier dysfunction or regulate enteroendocrine functions. Lastly, some recent data suggest that dietary amino acids might regulate the composition of the gut microbiota, but the relevance for the intestinal health remains to be determined. In summary, amino acid utilization by epithelial cells or by intestinal bacteria appears to play a pivotal regulator role for intestinal homeostasis. Thus, adequate dietary supply of amino acids represents a key determinant of gut health and functions.
10.1007/978-3-030-45328-2_1
Amino Acid Metabolism in the Liver: Nutritional and Physiological Significance.
Hou Yongqing,Hu Shengdi,Li Xinyu,He Wenliang,Wu Guoyao
Advances in experimental medicine and biology
The liver plays a central role in amino acid (AA) metabolism in humans and other animals. In all mammals, this organ synthesizes many AAs (including glutamate, glutamine, alanine, aspartate, asparagine, glycine, serine, and homoarginine), glucose, and glutathione (a major antioxidant). Similar biochemical reactions occur in the liver of birds except for those for arginine and glutamine hydrolysis, proline oxidation, and gluconeogenesis from AAs. In contrast to mammals and birds, the liver of fish has high rates of glutamate and glutamine oxidation for ATP production. In most animals (except for cats and possibly some of the other carnivores), the liver produces taurine from methionine or cysteine. However, the activity of this pathway is limited in human infants (particularly preterm infants) and is also low in adult humans as compared with rats, birds and livestock species (e.g., pigs, cattle and sheep). The liver exhibits metabolic zonation and intracellular compartmentation for ureagenesis, uric acid synthesis, and gluconeogenesis, as well as AA degradation and syntheses. Capitalizing on these extensive bases of knowledge, dietary supplementation with functional AAs (e.g., methionine, N-acetylcysteine, and glycine) to humans and other animals can alleviate or prevent oxidative stress and damage in the liver. Because liver diseases are common problems in humans and farm animals (including fish), much research is warranted to further both basic and applied research on hepatic AA metabolism and functions.
10.1007/978-3-030-45328-2_2
Ins and Outs of the TCA Cycle: The Central Role of Anaplerosis.
Inigo Melissa,Deja Stanisław,Burgess Shawn C
Annual review of nutrition
The reactions of the tricarboxylic acid (TCA) cycle allow the controlled combustion of fat and carbohydrate. In principle, TCA cycle intermediates are regenerated on every turn and can facilitate the oxidation of an infinite number of nutrient molecules. However, TCA cycle intermediates can be lost to cataplerotic pathways that provide precursors for biosynthesis, and they must be replaced by anaplerotic pathways that regenerate these intermediates. Together, anaplerosis and cataplerosis help regulate rates of biosynthesis by dictating precursor supply, and they play underappreciated roles in catabolism and cellular energy status. They facilitate recycling pathways and nitrogen trafficking necessary for catabolism, and they influence redox state and oxidative capacity by altering TCA cycle intermediate concentrations. These functions vary widely by tissue and play emerging roles in disease. This article reviews the roles of anaplerosis and cataplerosis in various tissues and discusses how they alter carbon transitions, and highlights their contribution to mechanisms of disease.
10.1146/annurev-nutr-120420-025558
The Roles of Cytoplasmic Lipid Droplets in Modulating Intestinal Uptake of Dietary Fat.
Zembroski Alyssa S,Xiao Changting,Buhman Kimberly K
Annual review of nutrition
Dietary fat absorption is required for health but also contributes to hyperlipidemia and metabolic disease when dysregulated. One step in the process of dietary fat absorption is the formation of cytoplasmic lipid droplets (CLDs) in small intestinal enterocytes; these CLDs serve as dynamic triacylglycerol storage organelles that influence the rate at which dietary fat is absorbed. Recent studies have uncovered novel factors regulating enterocyte CLD metabolism that in turn influence the absorption of dietary fat. These include peroxisome proliferator-activated receptor α activation, compartmentalization of different lipid pools, the gut microbiome, liver X receptor and farnesoid X receptor activation, obesity, and physiological factors stimulating CLD mobilization. Understanding how enterocyte CLD metabolism is regulated is key in modulating the absorption of dietary fat in the prevention of hyperlipidemia and its associated metabolic disorders.
10.1146/annurev-nutr-110320-013657
Intestinal Amino Acid Transport and Metabolic Health.
Annual review of nutrition
Amino acids derived from protein digestion are important nutrients for the growth and maintenance of organisms. Approximately half of the 20 proteinogenic amino acids can be synthesized by mammalian organisms, while the other half are essential and must be acquired from the nutrition. Absorption of amino acids is mediated by a set of amino acid transporters together with transport of di- and tripeptides. They provide amino acids for systemic needs and for enterocyte metabolism. Absorption is largely complete at the end of the small intestine. The large intestine mediates the uptake of amino acids derived from bacterial metabolism and endogenous sources. Lack of amino acid transporters and peptide transporter delays the absorption of amino acids and changes sensing and usage of amino acids by the intestine. This can affect metabolic health through amino acid restriction, sensing of amino acids, and production of antimicrobial peptides.
10.1146/annurev-nutr-061121-094344