What Is Metabolism?

Metabolism is the complete set of enzyme-catalyzed chemical reactions that sustain a living cell or organism, converting nutrients into energy, building the molecules the cell needs, and disposing of waste products. It sits at the junction of biochemistry and physiology, since the same reaction network can be described as a graph of chemical transformations or as the process that sets an organism's energy requirement. Every reaction in the network is thermodynamically constrained, and the coupling of unfavorable reactions to favorable ones through shared intermediates is what allows a cell to build order against the direction of spontaneous chemistry.

The network is conventionally divided into catabolism, which degrades complex molecules and releases energy, and anabolism, which consumes energy to synthesize macromolecules. The two run concurrently because catabolism supplies the adenosine triphosphate and reducing equivalents that anabolism spends, a relationship set out in clinical physiology reviews of metabolism.

Energy Currency and Redox Carriers

Cells do not release the energy of a nutrient in one step. Catabolic pathways extract it in small increments, capturing each increment in the phosphoanhydride bonds of ATP or in the reduced cofactors NADH, FADH2, and NADPH. ATP hydrolysis to ADP and inorganic phosphate releases about 30 kilojoules per mole under standard conditions, and closer to 50 at the concentrations actually found in a cell, enough to drive most coupled reactions but small enough that the cell can meter its expenditure. A human turns over an amount of ATP each day comparable to body mass, which is possible only because the pool is recycled continuously rather than stored. NADH and FADH2 carry electrons to the respiratory chain, while NADPH is reserved almost exclusively for biosynthesis and antioxidant defense, a separation of pools that keeps catabolic and anabolic flux independently controllable.

Central Pathways

Glucose catabolism runs through glycolysis in the cytosol, producing pyruvate, a small net yield of ATP, and NADH. Under aerobic conditions pyruvate is oxidized to acetyl-CoA and enters the citric acid cycle in the mitochondrial matrix, where successive oxidations release carbon dioxide and load the electron carriers. Oxidative phosphorylation then uses those electrons to pump protons across the inner mitochondrial membrane, and the resulting electrochemical gradient drives ATP synthase, a rotary molecular motor. Fatty acid beta-oxidation and amino acid catabolism feed the same cycle at different entry points, while gluconeogenesis, glycogen synthesis, and the pentose phosphate pathway run in the anabolic direction. Analyses of the compositional and evolutionary logic of metabolism argue that this core is highly conserved because a small number of reaction motifs suffice to connect available geochemical inputs to biomass.

Regulation and Metabolic Rate

Flux through the network is controlled at several timescales. Allosteric effectors act in milliseconds, covalent modification such as phosphorylation acts in seconds to minutes, and transcriptional control of enzyme abundance acts over hours. Hormones including insulin, glucagon, and the catecholamines coordinate these controls across tissues, and sensors such as AMP-activated protein kinase and mTOR link nutrient and energy status to growth decisions. At the whole-organism level, basal metabolic rate measures energy expenditure at rest and is estimated by indirect calorimetry from oxygen consumption and carbon dioxide production. Overviews of metabolism as an integrated physiological system describe how sex, age, body composition, thyroid status, and disease shift that rate.

Applications

Metabolism has applications in a wide range of disciplines, including:

• Clinical medicine, in diabetes, obesity, and inborn errors of metabolism
• Metabolic engineering, where pathways are redesigned in microbes to produce fuels and chemicals
• Systems biology, through genome-scale models and flux balance analysis
• Pharmacology, in drug metabolism, clearance prediction, and cancer metabolism targeting
• Sports science and nutrition, including substrate utilization and energy expenditure measurement
• Biosensor and wearable device design for continuous glucose and lactate monitoring