ADP-ribosyl Cyclase
Antigens, CD38
Adenylate Cyclase
Guanylate Cyclase
NAD+ Nucleosidase
NAD
Adenylate Cyclase Toxin
Models, Molecular
Adenosine Diphosphate
Purification and characterization of ADP-ribosyl cyclase from Euglena gracilis. (1/575)
ADP-ribosyl cyclase, which catalyzes the conversion from NAD+ to cyclic adenosine diphosphoribose (cADPR), is proposed to participate in cell cycle regulation in Euglena gracilis. This enzyme, which was found as a membrane-bound protein, was purified almost the homogeneity after solubilization with deoxycholate, and found to be a monomeric protein with a molecular mass of 40 kDa. Its Km value for NAD+ was estimated to be 0.4 mM, and cADPR, a product of the enzyme, inhibited the enzyme competitively with respect to NAD+ whereas another product, nicotinamide, showed noncompetitive (mixed-type) inhibition. In contrast to mammalian CD38 and BST-1, Euglena ADP-ribosyl cyclase lacked cADPR hydrolase activity. (+info)Characterization of viral dynamics in human immunodeficiency virus type 1-infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points. (2/575)
Biphasic plasma viral decays were modeled in 48 patients treated with ritonavir, zidovudine, and lamivudine. Estimated first- and second-phase decay rates were d1 as 0.47/day and d2 as 0.04/day. Interpatient differences in both decay rates were significant. The d1 was directly correlated with baseline CD4+, CD4+CD28+, and CD8+CD28+ T lymphocyte counts (P<.05) and inversely correlated with baseline virus load (P=.044) and the magnitude of CD4+ and CD8+ T lymphocyte recovery (P<.01). The d2 was directly correlated with baseline percentage of CD8+ T lymphocytes (P=.023), the CD8+CD38+ cell number (P=.024), and the level of IgG that binds to human immunodeficiency virus (HIV) type 1 gp120 (P=.02). Viral decay rates were not predictive of treatment failure or durability of viral suppression. These exploratory findings are consistent with a model in which immunologic factors contribute to elimination of HIV-infected cells and suggest a dynamic interplay between regulation of HIV expression and lymphocyte activation and recovery. (+info)Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. (3/575)
To define predictors of survival time in late human immunodeficiency virus type 1 (HIV-1) disease, long- and short-duration survivors were studied after their CD4+ T cells fell to +info)IL-5 induces IgG1 isotype switch recombination in mouse CD38-activated sIgD-positive B lymphocytes. (4/575)
Mouse B cells express CD38, whose ligation by anti-CD38 Ab induces their proliferation and protection from apoptosis. We previously showed that stimulation of mouse splenic B cells with IL-5 together with CS/2, an anti-mouse CD38 mAb, induces production of IgG1 and IgM. Here we examined the role of IL-5 and CS/2 in the expression of germline gamma1 transcripts and the generation of reciprocal products forming DNA circles as byproducts of mu-gamma1 switch recombination. By itself, CS/2 induced significant expression of germline gamma1 transcripts in splenic naive B cells, whereas IL-5 neither induced nor enhanced germline gamma1 expression. Increased cellular content of reciprocal product, which is characteristic of mu-gamma1 recombination, was not observed after culturing B cells with CS/2, but increased reciprocal product, along with high levels of lgG1 secretion, was found when B cells were cultured with CS/2 plus IL-5. Although IL-4 did not, by itself, induce mu-gamma1 recombination in B cells stimulated with CS/2, in conjunction with CS/2 plus IL-5, IL-4 dramatically enhanced sterile gamma1 transcription and IgG1 production. These results demonstrate that CD38 ligation induces only germline gamma1 transcription and that IL-5 promotes both mu-gamma1 switch recombination and lgG1 secretion in an IL-4-independent manner. (+info)Stable transduction of quiescent CD34(+)CD38(-) human hematopoietic cells by HIV-1-based lentiviral vectors. (5/575)
We compared the efficiency of transduction by an HIV-1-based lentiviral vector to that by a Moloney murine leukemia virus (MLV) retroviral vector, using stringent in vitro assays of primitive, quiescent human hematopoietic progenitor cells. Each construct contained the enhanced green fluorescent protein (GFP) as a reporter gene. The lentiviral vector, but not the MLV vector, expressed GFP in nondivided CD34(+) cells (45.5% GFP+) and in CD34(+)CD38(-) cells in G0 (12.4% GFP+), 48 hr after transduction. However, GFP could also be detected short-term in CD34(+) cells transduced with a lentiviral vector that contained a mutated integrase gene. The level of stable transduction from integrated vector was determined after extended long-term bone marrow culture. Both MLV vectors and lentiviral vectors efficiently transduced cytokine-stimulated CD34(+) cells. The MLV vector did not transduce more primitive, quiescent CD34(+)CD38(-) cells (n = 8). In contrast, stable transduction of CD34(+)CD38(-) cells by the lentiviral vector was seen for over 15 weeks of extended long-term culture (9.2 +/- 5.2%, n = 7). GFP expression in clones from single CD34(+)CD38(-) cells confirmed efficient, stable lentiviral transduction in 29% of early and late-proliferating cells. In the absence of growth factors during transduction, only the lentiviral vector was able to transduce CD34(+) and CD34(+)CD38(-) cells (13.5 +/- 2.5%, n = 11 and 12.2 +/- 9.7%, n = 4, respectively). The lentiviral vector is clearly superior to the MLV vector for transduction of quiescent, primitive human hematopoietic progenitor cells and may provide therapeutically useful levels of gene transfer into human hematopoietic stem cells. (+info)The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38. (6/575)
Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate pattern of expression in leukocytes, although evidence is accumulating of its quite widespread expression in cells of nonvascular origin. CD38 is a member of a nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes whose substrate is NAD, a coenzyme ubiquitously distributed in nature. Functionally, CD38 is an eclectic molecule with the ability not only to catalyze but also to signal, to mobilize calcium, and to adhere to itself, to hyaluronan, and to other ligands. Interaction with CD38 on various leukocyte subpopulations has profound though diverse consequences on their life-span, but these effects seem to be independent of the enzymatic activity of the molecule. CD38 challenges our expectations of a surface molecule and we must sift through its many guises to unmask its true nature. (+info)Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus. (7/575)
Ca2+ released from presynaptic and postsynaptic intracellular stores plays important roles in activity-dependent synaptic plasticity, including long-term depression (LTD) of synaptic strength. At Schaffer collateral-CA1 synapses in the hippocampus, presynaptic ryanodine receptor-gated stores appear to mobilize some of the Ca2+ necessary to induce LTD. Cyclic ADP-ribose (cADPR) has recently been proposed as an endogenous activator of ryanodine receptors in sea urchin eggs and several mammalian cell types. Here, we provide evidence that cADPR-mediated signaling pathways play a key role in inducing LTD. We show that biochemical production of cGMP increases cADPR concentration in hippocampal slices in vitro, and that blockade of cGMP-dependent protein kinase, cADPR receptors, or ryanodine-sensitive Ca2+ stores each prevent the induction of LTD at Schaffer collateral-CA1 synapses. A lack of effect of postsynaptic infusion of either cADPR antagonist indicates a probable presynaptic site of action. (+info)Expression of CD28 and CD38 by CD8+ T lymphocytes in HIV-1 infection correlates with markers of disease severity and changes towards normalization under treatment. The Swiss HIV Cohort Study. (8/575)
The relationship between blood CD8+ T lymphocyte subsets, as defined by CD28 and CD38 expression, and plasma viraemia and CD4+ T cells in HIV-1 infection was investigated. In a cross-sectional study of 46 patients with either no or stable anti-retroviral treatment, there was a strong negative correlation between the percentage of CD8+CD28- and the percentage of CD4+ T cells (r = -0.75, P < 0.0001), and a positive correlation between absolute numbers of CD8+CD28+ and CD4+ T cells (r = 0.56, P < 0.0001). In contrast, the expression of CD38 by CD8+ T lymphocytes correlated primarily with plasma viraemia (e.g. the percentage of CD38+ in CD8bright cells, r = 0.76, P < 0.0001). In the 6 months following triple therapy initiation in 32 subjects, there was a close correlation between changes (delta) in CD8+CD28+ or CD8+CD28- and in CD4+ T cells (e.g. delta % CD8+CD28+ versus delta % CD4+, r = 0.37, P = 0.0002; delta % CD8+CD28- versus delta % CD4+, r = -0.66, P < 0.0001). A marked decline of the number of CD8+ T cells expressing CD38 was also observed. These results suggest the existence of a T cell homeostasis mechanism operating in blood with CD4+ and CD8+CD28+ cells on the one hand, and with CD8+CD28- cells on the other. In addition, the percentage of CD38+ cells in CD8+ cells, generally considered an independent prognostic factor, could merely reflect plasma viral load. (+info)ADP-ribosyl cyclase is an enzyme that catalyzes the conversion of nicotinamide adenine dinucleotide (NAD+) to cyclic ADP-ribose (cADPR). This enzyme plays a role in intracellular signaling, particularly in calcium mobilization in various cell types including immune cells and neurons. The regulation of this enzyme has been implicated in several physiological processes as well as in the pathophysiology of some diseases such as cancer and neurodegenerative disorders.
CD38 is a type of antigen that is found on the surface of many different types of cells in the human body, including immune cells such as T-cells and B-cells. Antigens are substances (usually proteins) on the surface of cells that can be recognized by the immune system, triggering an immune response.
CD38 plays a role in several different cellular processes, including the regulation of calcium levels within cells, the production of energy in the form of ATP, and the modulation of immune responses. It is also involved in the activation and proliferation of T-cells and B-cells, which are critical components of the adaptive immune system.
CD38 can be targeted by certain types of immunotherapy, such as monoclonal antibodies, to help stimulate an immune response against cancer cells that express this antigen on their surface.
Adenylate cyclase is an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). It plays a crucial role in various cellular processes, including signal transduction and metabolism. Adenylate cyclase is activated by hormones and neurotransmitters that bind to G-protein-coupled receptors on the cell membrane, leading to the production of cAMP, which then acts as a second messenger to regulate various intracellular responses. There are several isoforms of adenylate cyclase, each with distinct regulatory properties and subcellular localization.
Ribose is a simple carbohydrate, specifically a monosaccharide, which means it is a single sugar unit. It is a type of sugar known as a pentose, containing five carbon atoms. Ribose is a vital component of ribonucleic acid (RNA), one of the essential molecules in all living cells, involved in the process of transcribing and translating genetic information from DNA to proteins. The term "ribose" can also refer to any sugar alcohol derived from it, such as D-ribose or Ribitol.
Guanylate cyclase is an enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), which acts as a second messenger in various cellular signaling pathways. There are two main types of guanylate cyclases: soluble and membrane-bound. Soluble guanylate cyclase is activated by nitric oxide, while membrane-bound guanylate cyclase can be activated by natriuretic peptides. The increased levels of cGMP produced by guanylate cyclase can lead to a variety of cellular responses, including smooth muscle relaxation, neurotransmitter release, and regulation of ion channels. Dysregulation of guanylate cyclase activity has been implicated in several diseases, such as hypertension, heart failure, and cancer.
NAD+ nucleosidase, also known as NMN hydrolase or nicotinamide mononucleotide hydrolase, is an enzyme that catalyzes the hydrolysis of nicotinamide mononucleotide (NMN) to produce nicotinamide and 5-phosphoribosyl-1-pyrophosphate (PRPP). NAD+ (nicotinamide adenine dinucleotide) is a crucial coenzyme involved in various redox reactions in the body, and its biosynthesis involves several steps, one of which is the conversion of nicotinamide to NMN by the enzyme nicotinamide phosphoribosyltransferase (NAMPT).
The hydrolysis of NMN to nicotinamide and PRPP by NAD+ nucleosidase is a rate-limiting step in the salvage pathway of NAD+ biosynthesis, which recycles nicotinamide back to NMN and then to NAD+. Therefore, NAD+ nucleosidase plays an essential role in maintaining NAD+ homeostasis in the body.
Deficiencies or mutations in NAD+ nucleosidase can lead to various metabolic disorders, including neurological and cardiovascular diseases, as well as aging-related conditions associated with decreased NAD+ levels.
NAD (Nicotinamide Adenine Dinucleotide) is a coenzyme found in all living cells. It plays an essential role in cellular metabolism, particularly in redox reactions, where it acts as an electron carrier. NAD exists in two forms: NAD+, which accepts electrons and becomes reduced to NADH. This pairing of NAD+/NADH is involved in many fundamental biological processes such as generating energy in the form of ATP during cellular respiration, and serving as a critical cofactor for various enzymes that regulate cellular functions like DNA repair, gene expression, and cell death.
Maintaining optimal levels of NAD+/NADH is crucial for overall health and longevity, as it declines with age and in certain disease states. Therefore, strategies to boost NAD+ levels are being actively researched for their potential therapeutic benefits in various conditions such as aging, neurodegenerative disorders, and metabolic diseases.
Adenylate cyclase toxin is a type of exotoxin produced by certain bacteria, including Bordetella pertussis (the causative agent of whooping cough) and Vibrio cholerae. This toxin functions by entering host cells and catalyzing the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), leading to increased intracellular cAMP levels.
The elevated cAMP levels can disrupt various cellular processes, such as signal transduction and ion transport, resulting in a range of physiological effects that contribute to the pathogenesis of the bacterial infection. For example, in the case of Bordetella pertussis, adenylate cyclase toxin impairs the function of immune cells, allowing the bacteria to evade host defenses and establish a successful infection.
In summary, adenylate cyclase toxin is a virulence factor produced by certain pathogenic bacteria that increases intracellular cAMP levels in host cells, leading to disrupted cellular processes and contributing to bacterial pathogenesis.
In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."
1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.
2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.
3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.
4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).
Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.
Molecular models are three-dimensional representations of molecular structures that are used in the field of molecular biology and chemistry to visualize and understand the spatial arrangement of atoms and bonds within a molecule. These models can be physical or computer-generated and allow researchers to study the shape, size, and behavior of molecules, which is crucial for understanding their function and interactions with other molecules.
Physical molecular models are often made up of balls (representing atoms) connected by rods or sticks (representing bonds). These models can be constructed manually using materials such as plastic or wooden balls and rods, or they can be created using 3D printing technology.
Computer-generated molecular models, on the other hand, are created using specialized software that allows researchers to visualize and manipulate molecular structures in three dimensions. These models can be used to simulate molecular interactions, predict molecular behavior, and design new drugs or chemicals with specific properties. Overall, molecular models play a critical role in advancing our understanding of molecular structures and their functions.
Adenosine diphosphate (ADP) is a chemical compound that plays a crucial role in energy transfer within cells. It is a nucleotide, which consists of a adenosine molecule (a sugar molecule called ribose attached to a nitrogenous base called adenine) and two phosphate groups.
In the cell, ADP functions as an intermediate in the conversion of energy from one form to another. When a high-energy phosphate bond in ADP is broken, energy is released and ADP is converted to adenosine triphosphate (ATP), which serves as the main energy currency of the cell. Conversely, when ATP donates a phosphate group to another molecule, it is converted back to ADP, releasing energy for the cell to use.
ADP also plays a role in blood clotting and other physiological processes. In the coagulation cascade, ADP released from damaged red blood cells can help activate platelets and initiate the formation of a blood clot.
Substrate specificity in the context of medical biochemistry and enzymology refers to the ability of an enzyme to selectively bind and catalyze a chemical reaction with a particular substrate (or a group of similar substrates) while discriminating against other molecules that are not substrates. This specificity arises from the three-dimensional structure of the enzyme, which has evolved to match the shape, charge distribution, and functional groups of its physiological substrate(s).
Substrate specificity is a fundamental property of enzymes that enables them to carry out highly selective chemical transformations in the complex cellular environment. The active site of an enzyme, where the catalysis takes place, has a unique conformation that complements the shape and charge distribution of its substrate(s). This ensures efficient recognition, binding, and conversion of the substrate into the desired product while minimizing unwanted side reactions with other molecules.
Substrate specificity can be categorized as:
1. Absolute specificity: An enzyme that can only act on a single substrate or a very narrow group of structurally related substrates, showing no activity towards any other molecule.
2. Group specificity: An enzyme that prefers to act on a particular functional group or class of compounds but can still accommodate minor structural variations within the substrate.
3. Broad or promiscuous specificity: An enzyme that can act on a wide range of structurally diverse substrates, albeit with varying catalytic efficiencies.
Understanding substrate specificity is crucial for elucidating enzymatic mechanisms, designing drugs that target specific enzymes or pathways, and developing biotechnological applications that rely on the controlled manipulation of enzyme activities.