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Acetaldehyde: A toxic product that results from the breakdown of alcohol by the enzyme alcohol dehydrogenase.

Adenosine triphosphate (ATP): A molecule, generated largely in the mitochondria, that provides the energy needed for many key metabolic reactions.

Alcohol dehydrogenase (ADH): An enzyme that breaks down alcohol by oxidation, converting it to acetaldehyde. (See cytochrome P450.)

ALD: Alcoholic liver disease.

Amino acids: The building blocks of proteins. Twenty different amino acids are found in human proteins; examples include lysine and methionine.

Antibody: A protein produced by certain immune cells that recognizes and binds to foreign proteins, leading to the destruction of those proteins.

Antioxidant: A substance such as glutathione and vitamins A and E or an enzyme that inhibits oxidation, serving as a defense against harmful free radicals.

Apoptosis: Cell death in which the affected cell participates by activating a cascade of biochemical reactions that lead to death. (See necrosis.)

Ascites: Accumulation of fluid in the abdomen, one of the most common complications of advanced liver disease. The presence of ascites generally indicates a poor prognosis and high likelihood of death.

Central vein: Blood exits each liver lobule by way of the central vein, which feeds into the hepatic vein.

Cirrhosis: The most advanced form of liver disease, characterized by extensive scarring that stiffens blood vessels and distorts the internal structure of the liver, severely impairing its function. Although alcoholic cirrhosis often is progressive and fatal, it may stabilize with abstinence.

Collagen: The major protein of fibrous connective tissue (e.g., tendons and ligaments) involved in the production of scar tissue; produced in the liver by stellate cells.

Cytochrome P450: A family of cytochromes, one of which (CYP2E1) can oxidize alcohol to form acetaldehyde. Most alcohol taken into the body is oxidized by alcohol dehydrogenase; high alcohol levels stimulate CYP2E1 activity.

Cytochromes: Specialized enzymes within mitochondria and other cell structures. Different cytochromes play important roles in metabolizing toxic substances, drugs, and other chemicals, as well as in producing adenosine triphosphate (ATP).

Cytokines: A family of molecules, produced primarily by cells of the immune system, which regulate cellular interactions and other functions. Many cytokines play important roles in initiating and regulating inflammation.

Cytoskeleton: The filaments and microtubules that serve to give the cell shape and coherence.

Cytosol: Fluid contained within the cell, where several biochemical reactions (e.g., glycolysis) take place.

DNA: A family of large molecules within the cells of an organism that carry genetic information specifying the structure of proteins.

Endotoxin: A highly toxic chemical component of the cell walls of bacteria that occur normally in the intestine. Endotoxin can be released into the bloodstream when the bacteria die.

Endocytosis: Mechanism by which specific molecules are ingested into the cell.

Endoplasmic reticulum: A system of folded membranes that loop back and forth, spreading throughout the cytoplasm and providing a large surface area for cell reactions.

Enzyme: A substance, usually a protein, that directs and accelerates chemical reactions in the body but does not itself undergo permanent change.

Extracellular matrix: The body substance within which tissue cells are embedded.

Fatty acids: A building block of fat molecules. Alcohol interferes with the normal metabolism of fatty acids and promotes the deposit of dietary fat in the liver.

Fibrosis: The formation of scar tissue.

Free radicals: Highly reactive molecular fragments that frequently contain oxygen. (See reactive oxygen species.)

Glutathione (GSH): An antioxidant molecule found naturally in the body, composed of three amino acids (i.e., glutamate, cysteine, and glycine).

Hepatic encephalopathy: A potentially fatal brain disorder that results when prolonged liver dysfunction caused by excessive alcohol consumption leads to the accumulation of toxic substances in the brain.

Hepatic vein: A large vessel that receives blood after it has passed through the central veins of the liver lobules.

Hepatitis: Generalized inflammation of the liver, often accompanied by tissue death and fibrosis. Alcoholic hepatitis can be fatal, but may be reversible with abstinence.

Hepatocytes: The principal cells of the liver, which carry out most of the liver’s metabolic activities.

Hypoxia: Lower–than–normal levels of oxygen.

Inflammation: A defensive response to local tissue injury or infection, serving to prevent the spread of injury and activate the immune system; regulated by cytokines. Prolonged or excessive inflammation can damage healthy tissue, as in alcoholic liver disease.

Interferons: A group of proteins that increase the resistance of cells to viral infection. Interferons also act as cytokines and can enhance some immune responses.

Interleukins: Cytokines of the immune system.

Intragastric infusion model: A method of rigorously controlling animals’ consumption of alcohol and dietary nutrients by feeding a liquid diet through a tube permanently inserted in the stomach. Used with rats and mice, this model also allows researchers to monitor alcohol intake daily without having to obtain blood.

Kupffer cells: Specialized immune cells in the liver that filter bacteria and other foreign substances from the blood and produce antibodies and cytokines. (See also sinusoids.)

Lipid peroxidation: The sequential breakdown of fatty substances in cells by chemical oxidation, leading eventually to the destruction of membranes within and surrounding the cell.

Lipids: Fatty substances, including simple fats, their major components (i.e., fatty acids), and various fat–soluble substances (e.g., cholesterol).

Lobule: A cylindrical structure about 2 millimeters in diameter, the lobule is the basic functional unit of the liver. The liver can be composed of up to 100,000 lobules.

Macrophage: A phagocyte residing in tissues throughout the body. In addition to ingesting foreign particles and microorganisms, macrophages synthesize proteins and other substances important in inflammatory responses, including cytokines. Macrophages that reside in the liver are called Kupffer cells.

Metabolism: The totality of chemical reactions occurring in a cell, an organ, or the body. The term sometimes is applied more narrowly to the breakdown of a particular substance (e.g., alcohol) by specific enzymes.

Microsomal ethanol–oxidizing system (MEOS): An enzyme system that breaks down alcohol and generates toxic products such as acetaldehyde and oxygen radicals.

Mitochondria: Structures within cells that generate most of the cells’ energy through the production of adenosine triphosphate (ATP).

NAD/NADH: Nicotinamide adenine dinucleotide (NAD) is a molecule that binds with hydrogen atoms during alcohol metabolism and becomes reduced NAD, or NADH. NAD and NADH move hydrogen atoms back and forth between various oxidation–reduction reactions, helping to maintain balance between oxidation and reduction in the cell.

Necrosis: Cell death that occurs in response to adverse conditions in the cell’s environment. (See apoptosis.)

Oxidation: A chemical reaction that usually involves removing a hydrogen atom from a molecule or adding oxygen to it, or both. (See reduction.)

Oxidative stress: An imbalance between oxidants (e.g., free radicals) and antioxidants that can lead to excessive oxidation and cell damage.

Periportal: Referring to the region of a liver lobule adjacent to a branch of the portal vein.

Perivenous: Referring to the region of a liver lobule surrounding a branch of the hepatic vein.

Phagocyte: A white blood cell capable of ingesting foreign particles and microorganisms. Phagocytes include monocytes, macrophages, and neutrophils.

Plasma membrane: The outer membrane of a cell. Also called the cell membrane or cell wall.

Portal vein: A large blood vessel that carries dissolved nutrients from the intestine directly to the liver.

Proteinase: A type of enzyme that catalyzes the breakdown of proteins. (See proteolysis.)

Proteins: Large molecules composed of long chains of amino acids linked together. Proteins help maintain the cell’s structure and participate in many biological functions, including the regulation of metabolic reactions. The shape and function of a protein is determined by the sequence of its amino acids.

Proteolysis: The breakdown, or degradation, of proteins into their building blocks, the amino acids. Proteolysis is essential for cell survival because some proteins must be broken down in order to carry out their biological functions, and because resulting amino acids are converted into energy molecules or recycled to produce new proteins. (See proteinase.)

Reactive oxygen species (ROS): Highly reactive oxygen–containing free radicals that are generated during oxidative metabolism. ROS can react with and damage lipids, proteins, and DNA in cells, causing oxidative stress. Common ROS include hydrogen peroxide, superoxide radicals, and hydroxyl radicals.

Receptor: A protein on the surface of a cell that recognizes and binds to chemical messengers.

Reduction: The reverse of oxidation, reduction is a chemical reaction that usually involves removing an oxygen atom from a molecule, or adding hydrogen to it, or both.

Respiratory chain: The electron transport system located in the mitochondria, in which electrons released by NADH are passed on to a series of other molecules that first accept the electrons and then pass them on to the next molecule in the chain. Finally. the electrons are transferred to oxygen to generate water. These successive reactions provide enough energy to drive the synthesis of ATP molecules.

Sinusoids: Channels in a liver lobule that conduct blood and nutrients to the hepatocytes, similar to capillaries in other organs. Sinusoids are lined with Kupffer cells.

Stellate cell: A star–shaped liver cell that serves as the primary storage site for vitamin A compounds and fat molecules; activation of stellate cells plays a central role in the development of fibrosis.

Superoxide: A destructive reactive oxygen species produced as a byproduct of some oxidation reactions.

Tumor necrosis factor alpha (TNF–α): A type of cytokine that promotes inflammatory responses, stimulates neutrophils and macrophages, induces fever, and induces macrophages to produce cytokines.

Prepared: October 2004