Drug metabolismDrug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin.
HepatotoxicityHepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval. The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. paracetamol) and sometimes even when introduced within therapeutic ranges (e.
Liver diseaseLiver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. File:Ground glass hepatocytes high mag cropped 2.jpg|Ground glass hepatocytes File:Primary biliary cirrhosis intermed mag much cropping.jpg|Primary biliary cirrhosis File:Buddchiari2.PNG|Budd-chiari syndrome File:Non-alcoholic_fatty_liver_disease1.
LiverThe liver is a major metabolic organ only found in vertebrate animals, which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is located in the right upper quadrant of the abdomen, below the diaphragm and mostly shielded by the lower right rib cage. Its other metabolic roles include carbohydrate metabolism, the production of hormones, conversion and storage of nutrients such as glucose and glycogen, and the decomposition of red blood cells.
Acute liver failureAcute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complications are hepatic encephalopathy and impaired protein synthesis (as measured by the levels of serum albumin and the prothrombin time in the blood). The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes.
ToxicationToxication, toxification or toxicity exaltation is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. The conversion can be caused by enzymatic metabolism in the organisms, as well as by abiotic chemical reactions. While the parent drug are usually less active, both the parent drug and its metabolite can be chemically active and cause toxicity, leading to mutagenesis, teratogenesis, and carcinogenesis.
Cytochrome P450Cytochromes P450 (P450s or CYPs) are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism.
Paracetamol poisoningParacetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These symptoms include feeling tired, abdominal pain, or nausea. This is typically followed by absence of symptoms for a couple of days, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure.
Reactive oxygen speciesIn chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () produces superoxide (), which is the precursor to most other reactive oxygen species: O2{} + e^- -> \ ^\bullet O2- Dismutation of superoxide produces hydrogen peroxide (): 2 H+{} + 2 \ ^\bullet O2^-{} -> H2O2{} + O2 Hydrogen peroxide in turn may be partially reduced, thus forming hydroxide ions and hydroxyl radicals (), or fully reduced to water: H2O2{} + e^- -> HO^-{} + \ ^\bullet OH 2 H+ + 2 e- + H2O2 -> 2 H2O In a biological context, ROS are byproducts of the normal metabolism of oxygen.
Drug developmentDrug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug.
Non-alcoholic fatty liver diseaseMetabolic (dysfunction) associated fatty liver disease (MAFLD) was previously known as non-alcoholic fatty liver disease (NAFLD) until renamed in 2023 by a global consensus panel composed mostly of hepatology researchers and clinicians. The term metabolic dysfunction-associated steatotic liver disease (MASLD) is also used. MAFLD is excessive fat build-up in the liver without another clear cause such as alcohol use.
MetabolismMetabolism (məˈtæbəlɪzəm, from μεταβολή metabolē, "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments.
AcetylationIn chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed acetate esters or simply acetates. Deacetylation is the opposite reaction, the removal of an acetyl group from a chemical compound. Deacylations "play crucial roles in gene transcription and most likely in all eukaryotic biological processes that involve chromatin". Acetylation is one type of post-translational modification of proteins.
Metabolic pathwayIn biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes. In most cases of a metabolic pathway, the product of one enzyme acts as the substrate for the next. However, side products are considered waste and removed from the cell. These enzymes often require dietary minerals, vitamins, and other cofactors to function.
GlutathioneGlutathione (GSH, ˌɡluːtəˈθaɪəʊn) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine.
Glucuronic acidGlucuronic acid (from Greek γλεῦκος "wine, must" and οὖρον "urine") is a uronic acid that was first isolated from urine (hence the name "uronic acid"). It is found in many gums such as gum arabic ( () 18%), xanthan, and kombucha tea and is important for the metabolism of microorganisms, plants and animals. Glucuronic acid is a sugar acid derived from glucose, with its sixth carbon atom oxidized to a carboxylic acid. In living beings, this primary oxidation occurs with UDP-α-D-glucose (UDPG), not with the free sugar.
DNA methylationDNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis.
Histone acetylation and deacetylationHistone acetylation and deacetylation are the processes by which the lysine residues within the N-terminal tail protruding from the histone core of the nucleosome are acetylated and deacetylated as part of gene regulation. Histone acetylation and deacetylation are essential parts of gene regulation. These reactions are typically catalysed by enzymes with "histone acetyltransferase" (HAT) or "histone deacetylase" (HDAC) activity. Acetylation is the process where an acetyl functional group is transferred from one molecule (in this case, acetyl coenzyme A) to another.
Drug designDrug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it.
MethylationIn the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and the biological sciences. In biological systems, methylation is catalyzed by enzymes; such methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA processing.
