Metabolic Control

Homeostasis is the steady state of equilibrium. Similarly, in biochemistry, energy homeostasis is the balance point between energy supplied and energy dissipated (i.e., a constant energy state) that the human body seeks to maintain for optimal performance. The hypothalamus plays a central role in regulating energy homeostasis. Inefficient energy homeostasis is thought to be a major factor in the obesity epidemic. Many models have been proposed to explain and further understand the mechanism of energy homeostasis.

Fatty acid metabolism includes the processes of either breaking down fatty acids to generate energy (catabolic) or creating fatty acids for storage or use (anabolic). Besides being a source of energy, fatty acids can also be utilized for cellular membranes or signaling molecules. Synthesis and beta oxidation are almost the reverse of each other, and special reactions are required for variations (unsaturated fatty acids, very-long-chain fatty acids (VLCFAs)). Synthesis occurs in the cell cytoplasm, while oxidation occurs in mitochondria. Shuttling across membranes within a cell requires additional processes, such as the citrate and carnitine shuttles. In certain physiologic states, an increase in fatty acid oxidation can lead to the production of ketone bodies, which can also be utilized as an energy source, particularly in the brain and muscles.

Glycogen is a branched polymer and the storage form of carbohydrates in the human body. Major sites of storage are the liver and skeletal muscles. Glycogen is the main source of energy during fasting or in between meals. Glycogen provides energy for up to 18 hours, after which energy requirements are met by fatty acid oxidation. The 2 metabolic pathways of glycogen are glycogenesis (glycogen synthesis) and glycogenolysis (glycogen breakdown). The key regulatory enzymes in these processes are glycogen synthase (in glycogenesis) and glycogen phosphorylase (in glycogenolysis). These pathways proceed depending on the energy needs of the cells, generally modulated by hormonal and allosteric regulators. Abnormal accumulation of glycogen occurs with enzyme deficiencies causing different types of glycogen storage disorders.

Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. There are several forms of insulin, and they differ in their time of onset, peak effect, and duration. Insulin can be classified as fast acting, short acting, intermediate acting, or long acting. A combination of classes can be used to maintain glucose control throughout the day. Common adverse effects include hypoglycemia, weight gain after initiation of an insulin regimen, and local injection site changes.

Enzyme inhibitors bind to enzymes and decrease their activity. Enzyme activators bind to enzymes and increase their activity. Molecules that decrease the catalytic activity of enzymes can come in various forms, including reversible or irreversible inhibition. Reversible inhibition can be competitive, non-competitive, or uncompetitive.

Enzyme kinetics describes the sequence of enzyme-catalyzed reactions with a dependence on various parameters such as temperature, pH, and substrate concentration. The reaction rate is measured and the effects of varying the conditions of the reaction are investigated.

Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis and glycogenolysis are the 2 major ways the body produces glucose. Key enzymes for gluconeogenesis are pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase. Thus, gluconeogenesis becomes the main source of glycemic maintenance after glycogen stores are depleted.

The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. The pancreas is covered with a very thin connective tissue capsule that extends inward as septa, partitioning the gland into lobules. This organ has both exocrine and endocrine tissue. The exocrine portion is organized in grape-like clusters of acini, which are small sacs surrounding the terminal ends of pancreatic ducts. The cells lining the acini and ducts secrete products that make up pancreatic juices, which play a major role in digestion. The endocrine portion of the gland consists of circular islets interspersed between acini, which secrete glucagon, insulin, and somatostatin.

Lipid metabolism is the processing of lipids for energy use, energy storage, and structural component production. Lipid metabolism uses fats from dietary sources or from fat stores in the body. A complex series of processes involving digestion, absorption, and transport are required for the proper metabolism of lipids. Triacylglycerols are transported in body fluids by molecules called lipoproteins. Within the GI tract, metabolism of triacylglycerols may occur, facilitated by a group of enzymes called lipases. This process relies on preprocessing to make hydrophobic lipids soluble in order to accommodate hydrolysis and further processing.

Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis occurs in the cytoplasm and consists of 10 reactions, the net result of which is the conversion of 1 C6 glucose to 2 C3 pyruvate molecules. The free energy of this process is harvested to produce adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide hydride (NADH), key energy-yielding metabolites. The overall stoichiometry of the pathway is: glucose + 2 Pi + 2 ADP + 2 NAD+ > 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O (H+: hydrogen ion, Pi: phosphate ion, NAD+: nicotinamide adenine dinucleotide).

Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Enzymes have many functions, including macromolecule degradation and synthesis (catabolism and anabolism), signal transduction, energy generation (adenosine triphosphate [ATP]), ion pumps/active transport, defense and clearance reactions (oxidization, reduction, hydrolysis), cell regulation, movement (myosin ATPase, transport of intracellular substances), and immune responses.