Acetyl-coenzyme A (CoA)

Acetyl-coenzyme A (CoA) is an important intermediate of many biochemical pathways. For instance, acetyl-CoA is an important product of the mitochondrial metabolism of fatty acids and carbohydrates. Acetyl-CoA produced from these carbon substrates feeds into the mitochondrial tricarboxylic acid cycle (or Krebs cycle), which when coupled to the mitochondrial electron transport chain results in the production of energy (in the form of ATP).

Acetyl-coenzyme A carboxylase (ACC) 2

Acetyl-coenzyme A carboxylase (ACC) is a key enzyme involved in both the synthesis and metabolism of fatty acids. ACC produces malonyl coenzyme A, which is both a substrate for fatty acid biosynthesis and a potent inhibitor of mitochondrial fatty acid uptake. Heart and muscle primarily express ACC2, which is the isoform of ACC that is thought to be primarily involved in the regulation of fatty acid oxidation.

Acyl-CoA synthetase (MHC-ACS)

Long chain acyl-CoA synthetase is one of the first enzymes in the fatty acid metabolic pathway. It converts long chain fatty acids to long chain acyl-CoA within the cell. Long chain acyl-CoA is then either metabolized by the mitochondria to produce energy, or is used to produce membrane and cellular lipids. MHC-ACS refers to an experimental approach to selectively express acyl-CoA synthetase (ACS) in muscle. This is achieved by linking the ACS gene to the myosin heavy chain (MHC) promoter. The production of transgenic mice from embryonic stem cells that contain the MHC-ACS gene will result in mice that overexpress ACS targeted to muscle.

Acylation stimulating protein (ASP)

Acylation stimulating protein (ASP) is an adipocytederived protein that upregulates triacylglycerol synthesis in adipocytes. ASP has recently been suggested to play an important role in the regulation of lipoprotein metabolism and triacylglycerol storage. ASP also appears to have a role in the regulation of energy balance.

Adenylate cyclase

Adenylate cyclase is an enzyme that catalyzes the conversion of ATP to cAMP. cAMP is an important second messenger molecule involved in signal transduction. Adenylate cyclase is activated or inhibited by G proteins, which are coupled to membrane receptors, such as the ß-adrenergic receptor.

Adipokines

Adipokines is a term that is used to collectively describe a variety of signalling molecules that are released from adipose tissue. Examples of adipokines include adiponectin, and cytokines such as TNF-1a.

Adiponectin

Adiponectin is an adipokine that is released from adipose tissue. It is an important signalling molecule that acts centrally at the level of the hypothalamus to decrease food intake, and peripherally to modify fatty acid and glucose metabolism. Low levels of adiponectin are associated with obesity and insulin resistance.

Adipophilin

Adipophilin is a protein that is involved in lipid transport or storage. Adipophilin, which was initially described in adipocytes, is associated with lipid accumulation in cells. It is found in many cells and may be a new marker for the identification of specialized differentiated cells containing lipid droplets and for diseases associated with fataccumulating cells.

Adipsin

Adipsin is one of a number of physiologically important proteins excreted by adipocytes. Adipsin has a role in the regulation of energy intake and storage, and works with acylation stimulating protein to regulate lipoprotein metabolism and triacylglycerol storage. In the gut, adipsin facilitates removal of lipid from chylomicrons.

Agouti protein

Agouti protein is an endogenous antagonist of melanocortin receptors that have been implicated as part of the hypothalamic mechanism that mediates leptin-induced hypophagia. The agouti protein has a role in controlling energy homeostasis and possibly human pigmentation.

Akt

Akt, which is sometimes called protein kinase B (PKB) is an intracellular kinase that is important in a number of cellular functions, including regulation of glucose metabolism and cell growth. It is a kinase in the insulin signalling pathway, and insulin activation of Akt will result in GLUT 4 translocation to the cell membrane, thereby stimulating glucose uptake. Overexpression of Akt in the heart can cause a marked hypertrophy of the muscle.

Aldehydes

An aldehyde is either a functional group consisting of a terminal carbonyl group or a compound containing a terminal carbonyl group. Aldehydes such as malondialdehyde are also products of free radical injury. Lipid hydroperoxides decompose to form a variety of products including malondialdehyde, which is used as an indicator of the oxidative damage of cells and tissues.

Algogenic

Is a medical term that refers to any stimulus or situation that causes pain.

Allele

An allele is one of two or more alternative forms of a gene at the same site in a chromosome. This determines the alternative characteristic of the inheritance.

Allosteric regulation of enzymes

Allosteric regulation of an enzyme involves the change in the shape and activity of an enzyme that results from molecular binding with a regulatory substance at a site other than the enzymatically active one. An example of this is binding of 5-adenosine monophosphate (AMP) to a regulatory site on AMPactivated protein kinase that results in an activation of the enzyme.

Alpha-myosin heavy chain

Muscle is made up of interacting thick and thin filaments that slide past each other to produce muscle contraction. The thick filaments consist mainly of myosin. Myosin is a very large molecule made up of two identical heavy chains (alpha-myosin heavy chains) and four light chains. The alpha-myosin heavy chain consists of an alpha helical coiled rod and a globular region.

Alphatocopherol

Alphatocopherol (or vitamin E) is an antioxidant that protects cell membranes from free radical-induced lipid peroxidation. Ubiquinone can recycle radical forms of vitamin E, thereby also protecting membrane phospholipids against peroxidation.

AMP-activated protein kinase (AMPK)

AMPK is a key kinase that controls many cellular processes, particularly pathways involved in cellular energy status. AMPK is activated during metabolic stress, where it then can either activate energy producing metabolic pathways or inhibit energy consuming pathways. For these reasons it has been termed a ‘‘fuel gauge’’ of the cell.

Anaerobic glycolysis

Anaerobic glycolysis is the first part of the metabolic pathway for glucose. The glycolysis pathway metabolizes glucose to pyruvate, and in the process produces energy in the form of ATP. The glycolytic pathway can be considered “anaerobic” since no oxygen is required for the production of ATP (unlike aerobic mitochondrial metabolism, which requires oxygen).

Angiopoietin

Angiopoietin is an important regulator of endothelial cell survival. One of the actions of angiopoietin reduces vascular permeability mediated by vascular endothelial growth factors.

Angiotensinogen

The renin-angiotensin system is widely known for its importance in controlling blood pressure, electrolyte homeostasis, and volume regulation. Angiotensinogen is an early intermediate of this pathway, and polymorphisms in this gene contribute to the pathogenesis of both hypertension and cardiovascular disease.

Annexin V

Annexin V, a calcium-binding protein, is widely present in various organs and tissues. Assaying annexin V is a method of assessing the degree of tissue apoptosis. High levels of plasma annexin V in patients with acute myocardial infarction, cardiac arrest, or severe trauma have also been suggested to reflect the severity of damage to the myocardium.

Anti-C-reactive protein (CRP) activity

C-reactive protein (CRP) is a protein that is produced in the acute phase of an inflammatory reaction. Recent interest has focused on the measurement of CRP as an indicator of various inflammatory diseases, as well as to assess the degree of cardiovascular risk. For example, measurement of CRP has been used to measure inflammation associated with an acute myocardial infarction or unstable angina. Anti-CRP is an antibody against CRP that can be used to assess CRP levels/activity in the serum of patients.

Antimyosin

Antimyosin antibody is an antibody that recognizes myosin in muscle cells. Since myosin is intracellular, myocardial uptake of antimyosin antibodies (ie, 111In-antimyosin) is used as a measure of necrotic cell injury.

Anti-tumor necrosis factor-α (TNFα)

Tumor necrosis factor-a (TNFa) is a cytokine that has diverse actions in the body. With regard to the heart, TNFa binds to cardiac receptors and mediates a number of cellular processes, including the promotion of apoptosis (programmed cell death), and activation of inducible nitric oxide synthase.

Apolipoprotein (apo) E

Apolipoprotein (apo) E is one of the proteins associated with circulating lipoproteins. Polymorphisms in the apo E gene result in the development of atherosclerosis and increase the risk for heart disease, stroke, and Alzheimer’s disease.

Apoptosis

Apoptosis is a process describing the programmed death of a cell. It involves a mechanism of cell death which is controlled by a complex intracellular signalling pathway. The mechanisms involved in apoptotic cell death and the role of apoptosis in cardiac pathology are presently an area of intense research interest.

Arachidonic acid pathway enzymes lipoxygenase

The lipoxygenase pathway is an important group of enzymes involved in the metabolism of arachidonic acid to leukotrienes. Leukotrienes have diverse biological actions in the body.

Arg302Gln amino acid substitution in the gamma-2 regulatory subunit (PRKAG2) of AMPK

PRKAG2 is the gene that encodes the gamma2 subunit of AMP-activated protein kinase (AMPK). Mutations in PRKAG2 have recently been shown to cause cardiac hypertrophy, cardiac glycogen accumulation, Wolff- Parkinson White syndrome and conduction system disease causing pre-excitation. One of these mutations involves the substitution of arginine for glutamine at the 302 amino acid position of the gamma2 subunit of AMPK. It is thought that this mutation decreases the activity of AMPK in the heart.

ATPase

ATPase are proteins that cleave adenosine triphosphate (ATP) to adenosine diphosphate (ADP). This reaction releases energy, which is usually used to drive some other energy-requiring reaction mediated by the ATPase. For instance, Na/K-ATPase pumps Na+ out of cells and K+ into cells using the energy generated from the ATPase reaction. Another example is myosin ATPase, where the energy generated by the ATPase is used for muscle contraction.

ATP-sensitive K+-channels

ATP-sensitive potassium (KATP) channels are potassium channels that are present in either the plasma membrane of the cell, or the mitochondrial membrane of the cell. These channels are inhibited by ATP, and the KATP in the plasma membrane serve to couple the metabolic status of the cell to its membrane potential. KATP regulates a number of cell actions, including muscle contractility (skeletal, cardiac and vascular smooth muscle). The opening of sarcolemmal and mitochondrial ATP-sensitive K(+) (KATP) channels in the heart is believed to mediate ischemic preconditioning, a phenomenon whereby brief periods of ischemia/reperfusion protect the heart against myocardial infarction.

A-Type lamins

A-Type lamins are intermediate filament proteins that belong to the lamina, a ubiquitous nuclear network. Naturally occurring mutations in these proteins have been shown to be responsible for several distinct diseases that display skeletal and/or cardiac muscle or peripheral nerve involvement.

Autacoids

Autacoids are organic substances produced in one cell type that act either on the same cell, or a cell nearby to produce a biological effect. Nitric oxide (NO) or prostaglandins are examples of autacoids.

Autophosphorylation

Autophosphorylation refers to a situation where a kinase can phosphorylate an identical kinase.

Bamiphylline

Bamiphylline is a specific A1 adenosine receptor antagonist. By inhibiting A1 receptors it antagonizes the actions of adenosine on these receptors. This includes any cardioprotective effects of adenosine in the ischemic heart.

Bradykinin

Bradykinin is a small peptide of the kinin group of proteins, consisting of nine amino acids. It is a potent endothelium-dependent vasodilator that causes contraction of non-vascular smooth muscle, increases vascular permeability and is also involved in the mechanism of pain.

Calcineurin

Calcineurin is a phosphatase that cleaves phosphate groups from proteins. This phosphatase has received a considerable research interest in cardiac hypertrophy, since activation of calcineurin can promote cell growth secondary to dephosphorylation of translocation nuclear factor of activated T-cell (NFAT). The dephosphorylated NFAT can then translocate to the nucleus and promote cell growth.

Calmodulin

Calmodulin is an important molecule that binds calcium and stimulates the activity of calmodulin-dependent kinases. Calmodulin mediates many important reactions in the cell, including excitation contraction coupling of muscle cells.

Calmodulin-dependent fashion

Calmodulin is an important molecule that binds calcium and stimulates the activity of calmodulin- dependent kinases. Calmodulin mediates many important reactions in the cell, including excitation-contraction coupling of muscle cells.

CamKll

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a kinase that is activated by Ca2+/calmodulin. This kinase regulates many cellular proteins, many of which are involved in the regulation of cellular calcium. Activation of CamKII has also been shown to induce cardiac hypertrophy.

Cardiotin

Cardiotin is a high molecular weight (300 kDa) constituent of cardiac muscle. It is a structural protein associated with the sarcoplasmic reticulum. The measurement of cardiotin has been used to characterize the morphology of cardiac cells.

Cariporide

Cariporide is a drug that inhibits an enzyme called the sodium-hydrogen exchanger. This exchanger exists in the membrane of cells, including the cardiomyocyte, and exchanges intracellular hydrogen for extracellular sodium. Inhibition of this enzyme prevents the accumulation of sodium inside the cell during ischemia. Cariporide has been tested in clinical trials for use in various forms of ischemic heart disease, and has shown some promise as a cardioprotective agent during coronary artery bypass surgery.

Carnitine palmitoyl transferase-1 (CPT-1)

Carnitine palmitoyl transferase-1 (CPT-1) is the ratelimiting enzyme involved in the uptake of fatty acids in the mitochondria. It converts fatty acyl-coenzyme A to fatty acylcarnitine, which is then transported into the mitochondria where it is further metabolized. CPT-1 is a highly regulated enzyme that prevents excess of fatty acids from being taken up into the mitochondria.

Carnitine-acylcarnitine translocase

Carnitinue acylcarnitine translocase is an important enzyme involved in the mitochondrial uptake of fatty acids. Carnitine-acylcarnitine translocase is the enzyme responsible for translocating acylcarnitine across the mitochondrial membrane in exchange for carnitine.

Carotenoids

Carotenoids are natural antioxidants that are abundant in fruit and vegetables. It has been proposed that the epidemiological association between high fruit and vegetable consumption and lower cancer rates may be related to an increased consumption of carotenoids.

Catalase

Catalase is a common enzyme that functions to catalyze the decomposition of hydrogen peroxide to water and oxygen. Catalase is an important anti-oxidant enzyme that protects the cell from free radical injury.

Catechin

Catechin is a flavonoid, sometimes called flavanol. Catechin has antioxidant properties and can prevent free radical injury. It is present in grapes and has been suggested to contribute to the antioxidant properties of wine.

Caveolin

Caveolie are invaginations in the plasma membrane of cells that represent subcompartments of the plasma membrane. Caveolins are caveolie coat proteins. Recent interest has focussed on the role of G-proteins associated with caveolins as a mechanism for transmembrane signalling.

Ceramides

Ceramides are specialized lipids that are derived from sphingomyelin and glycosphingolipids present in plasma membrane of cells. Various cytokines can release ceramide, which then act as important intracellular signalling molecules. Considerable interest has focused on ceramide as a signalling molecule in apoptosis (programmed cell death).

cGMP

cGMP stands for cyclic guanosine monophosphate. It is a very important intracellular signalling molecule in cells. In smooth muscle, an increase in cGMP results in vasodilation. The vasodilator effects of nitric oxide (NO) are mediated by cGMP.

Cholesterol ester transfer protein (CETP)

Cholesterol ester transfer protein (CETP) facilitates reverse cholesterol transport from high-density lipoprotein (HDL) to triacylglycerol-rich lipoproteins. High plasma levels of CETP are correlated with low HDL cholesterol levels, a strong risk factor for coronary artery disease.

Chromatin

Chromatin is the DNA-containing chromosomal material of the nucleus.

Chronic occlusion

Chronic occlusion usually refers to the sustained occlusion of a coronary blood vessel.

Conjugated dienes in circulating low-density lipoproteins

Conjugated dienes are a product of free radical reaction with lipids. The presence of conjugated dienes in circulating low-density lipoproteins is used as a marker of oxidant stress by free radicals.

Connexin 43

Gap junction channels are essential for intercellular communication between cardiac cells. Among the most abundant gap junction channel proteins is connexin 43.

CrCl level

CrCl is the abbreviation for creatinine clearance. Measurement of creatinine clearance rates is used to assess kidney function.

Creatine/phosphocreatine

Phosphocreatine is a chemical storage form of energy in cells. In times of increased energy demand, the high energy phosphate on phosphocreatine can be transferred to adenosine diphosphate (ADP) to form adenosine triphosphate (ATP) and creatine. ATP is then used by enzymes in energy requiring cellular processes. In times of low energy demand, the reverse reaction occurs, with creatine kinase catalyzing the formation of phosphocreatine and ADP from ATP and creatine. A creatine and phosphocreatine shuttle system is important in the transfer of high energy phosphates from mitochondria to the cytoplasm.

Cyclo-oxygenase

The cyclo-oxygenase enzymes are an important group of enzymes involved in the metabolism of arachidonic acid to prostaglandins. Prostaglandins have diverse biological actions in the body.

Cytochrome c

Cytochrome c is a mitochondrial protein that has an important electron-transport function in mitochondrial respiration. Recently, cytochrome c release from the mitochondria has been shown to be an important early event in the apoptotic (programmed cell death) pathway. Release of cytochrome c from the mitochondria triggers a series of events leading to cell death.

Cytochrome c oxidase

Cytochrome c oxidase is a mitochondrial enzyme that has an important role in the electron transport function of mitochondrial respiration. The oxidation of cytochrome c by cytochrome c oxidase is one of the steps that results in electron transport via this pathway. The electron transport chain transfers electrons through a number of different enzyme complexes which catalyze the pumping of protons out of the mitochondrial matrix. These protons can then pass back into the mitochondria via an enzyme called ATP synthase. The downhill electrochemical gradient of this process produces energy that results in the production of ATP from ADP. ATP is a form of chemical energy used in most cellular processes requiring energy.

Cytochrome P-450 mono-oxygenases

Cytochrome P-450 mono-oxygenases play an important role in steroid metabolism and in drug clearance in the liver.

Cytokines

Cytokines refer to a group of compounds that are produced under a variety of conditions, including the immune response and inflammatory reactions. Tumor necrosis factor-a and interleukin-1 are examples of two cytokines.

Cytoskeletal proteins

Cytoskeletal proteins are important structural proteins of the cell that have an important role in maintaining cell shape and structure.