Biochemistry: The transformations of molecules that form the basis of living systems.

Biomarker: An objective, measurable biochemical parameter that faithfully reflects a critical pathway to a disease or a critical pathway that predisposes to a disease (ultimate or proximal critical pathways).

Biomarkers of Disease: Biochemical or anatomic measures of definitively identified pathogenic loci; direct measures of progression or reversal of a fundamental underlying disease process.

Critical nodes: The key enzymatic loci controlling flux distributions through competing pathways; once identified, these represent the likely sites of genetic control and the prime targets for pharmaceutical or gene therapies.

Critical pathway: The biochemical steps that predispose to or culminate in a disease; the immediate biochemical fluxes or controlling processes that are responsible for a functional disorder (a clinical outcome). Can be proximal (early) or ultimate (late) in the biochemical genesis of a disease.

D₂O: Heavy water is deuterium oxide, or D₂O or ²H₂O. It is chemically the same as normal water, H₂O, but the hydrogen atoms are of the heavy isotope deuterium, in which the nucleus contains a neutron in addition to the proton found in the nucleus of any hydrogen atom.

Flux: The flow of molecules through a series of biochemical steps (i.e. a pathway); expressed as a rate, in units of chemical mass/time.

Flux distributions: The relative flux rates through competing pathways within a biochemical system; such patterns of fluxes are characteristic of and highly defended by biologic systems.

GAG: Glycosaminoglycan (GAG) is the polysaccharide unit that makes up proteoglycans, a molecule made of saccharides and proteins. GAGs are extracellular matrix molecules that help give tissues like cartilage their rigid structure.

Genotype: The entire genetic constitution of an individual.

In vivo: Occurring in the fully assembled, living organism; contrasted to events occurring in artificial or incompletely assembled systems ("ex vivo").

Kinetics: In biochemistry, the rates at which molecular transformations occur; contrasted to statics, the study of systems at rest or at a single moment in time.

Mass Spectrometry: Instrumental method for identifying the chemical constitution of a substance by separating gaseous ions according to their differing mass and charge. In a mass spectrometer, atoms or molecules in a sample are ionized by an electric beam. The ions are accelerated by an electric field and then deflected by a powerful magnet. Different ions are deflected to different degrees, allowing for measurement of abundances of different masses and therefore, isotopic enrichment of a sample.

Observability: In systems theory and simulation/modeling, the capacity of a portion of a system to be observed and measured; allows verification of behavior of a subsystem against the predictions of the larger model. In biology, flux through a node within a complex metabolic network represents a potentially observable portion of a system.

On-Mechanism: Activity upon the actual metabolic pathway or process that is the basis for disease in the intact complex system, such as the whole animal or man. Drugs that are "on-target" by binding to or inhibiting a targeted protein, kinase or receptor (e.g. VEGF), are often not "on-mechanism" (e.g. inhibit angiogenesis in the intact animal).

Pathway: A series of linked biochemical steps, with a beginning and an end; activity within a pathway takes the form of flux, or flow, of molecules; the network of pathways forms the biochemical repertoire or potential phenotypes of a biological system.

Phenotype: The entire physical, biochemical, and physiological makeup of an individual as determined both genetically and environmentally, as opposed to genotype.

Stable Isotope: Isotopes of an element have the same atomic number, but different atomic mass. Stable isotopes do not undergo radioactive decay as radio-isotopes do. Elements can exist in both stable and unstable (radioactive) forms. Most elements of biological interest (including C, H, O, N, and S) have two or more stable isotopes, with the lightest of these present in much greater abundance than the others. Among stable isotopes the most useful as biological tracers are the heavy isotopes of hydrogen, carbon and nitrogen. These elements are found in the earth, the atmosphere, and all organisms.

Translational medicine: It is the science of developing more predictive transitions from preclinical animal efficacy to human efficacy.

Ultra-sensitive MS: Highly sensitive mass spectrometers have been used to measure small differences in the ratio of isotopes in certain molecules to ascertain, for example, the isotopic enrichment of a stable isotope labeled biological sample.