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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Biochemical cascade | 2/9 | https://en.wikipedia.org/wiki/Biochemical_cascade | reference | science, encyclopedia | 2026-05-05T10:46:07.942614+00:00 | kb-cron |
=== Examples of biochemical cascades === In biochemistry, several important enzymatic cascades and signal transduction cascades participate in metabolic pathways or signaling networks, in which enzymes are usually involved to catalyze the reactions. For example, the tissue factor pathway in the coagulation cascade of secondary hemostasis is the primary pathway leading to fibrin formation, and thus, the initiation of blood coagulation. The pathways are a series of reactions, in which a zymogen (inactive enzyme precursor) of a serine protease and its glycoprotein co-factors are activated to become active components that then catalyze the next reaction in the cascade, ultimately resulting in cross-linked fibrin. Another example, sonic hedgehog signaling pathway, is one of the key regulators of embryonic development and is present in all bilaterians. Different parts of the embryo have different concentrations of hedgehog signaling proteins, which give cells information to make the embryo develop properly and correctly into a head or a tail. When the pathway malfunctions, it can result in diseases like basal cell carcinoma. Recent studies point to the role of hedgehog signaling in regulating adult stem cells involved in maintenance and regeneration of adult tissues. The pathway has also been implicated in the development of some cancers. Drugs that specifically target hedgehog signaling to fight diseases are being actively developed by a number of pharmaceutical companies. Most biochemical cascades are series of events, in which one event triggers the next, in a linear fashion. Biochemical cascades include:
The Complement system The Insulin Signaling Pathway The Sonic hedgehog Signaling Pathway The Wnt signaling pathway The JAK-STAT signaling pathway The Adrenergic receptor Pathways The Acetylcholine receptor Pathways The Mitogen-activated protein kinase cascade Conversely, negative cascades include events that are in a circular fashion, or can cause or be caused by multiple events. Negative cascades include:
Ischemic cascade
== Cell-specific biochemical cascades ==
=== Epithelial cells === Adhesion is an essential process to epithelial cells so that epithelium can be formed and cells can be in permanent contact with extracellular matrix and other cells. Several pathways exist to accomplish this communication and adhesion with environment. But the main signalling pathways are the cadherin and integrin pathways. The cadherin pathway is present in adhesion junctions or in desmosomes and it is responsible for epithelial adhesion and communication with adjacent cells. Cadherin is a transmembrane glycoprotein receptor that establishes contact with another cadherin present in the surface of a neighbour cell forming an adhesion complex. This adhesion complex is formed by β-catenin and α-catenin, and p120CAS is essential for its stabilization and regulation. This complex then binds to actin, leading to polymerization. For actin polymerization through the cadherin pathway, proteins of the Rho GTPases family are also involved. This complex is regulated by phosphorylation, which leads to downregulation of adhesion. Several factors can induce the phosphorylation, like EGF, HGF or v-Src. The cadherin pathway also has an important function in survival and proliferation because it regulates the concentration of cytoplasmic β-catenin. When β-catenin is free in the cytoplasm, normally it is degraded, however if the Wnt signalling is activated, β-catenin degradation is inhibited and it is translocated to the nucleus where it forms a complex with transcription factors. This leads to activation of genes responsible for cell proliferation and survival. So the cadherin-catenin complex is essential for cell fate regulation. Integrins are heterodimeric glycoprotein receptors that recognize proteins present in the extracellular matrix, like fibronectin and laminin. In order to function, integrins have to form complexes with ILK and Fak proteins. For adhesion to the extracellular matrix, ILK activate the Rac and Cdc42 proteins and leading to actin polymerization. ERK also leads to actin polymerization through activation of cPLA2. Recruitment of FAK by integrin leads to Akt activation and this inhibits pro-apoptotic factors like BAD and Bax. When adhesion through integrins do not occur the pro-apoptotic factors are not inhibited and resulting in apoptosis.
=== Hepatocytes === The hepatocyte is a complex and multifunctional differentiated cell whose cell response will be influenced by the zone in hepatic lobule, because concentrations of oxygen and toxic substances present in the hepatic sinusoids change from periportal zone to centrilobular zone10. The hepatocytes of the intermediate zone have the appropriate morphological and functional features since they have the environment with average concentrations of oxygen and other substances. This specialized cell is capable of:
Regulate glucose metabolism Via cAMP/PKA/TORC (transducers of regulated CREB)/CRE, PIP3 /PKB and PLC /IP3 Expression of enzymes for synthesis, storage and distribution of glucose Synthesis of acute phase proteins Via JAK /STAT /APRE (acute phase response element) Expression of C-reactive protein, globulin protease inhibitors, complement, coagulation and fibrinolytic systems and iron homeostasis Regulate iron homeostasis (acute phase independent) Via Smads /HAMP Hepcidin expression Regulate lipid metabolism Via LXR /LXRE (LXR response element) Expression of ApoE CETP, FAS and LPL Exocrine production of bile salts and other compounds Via LXR /LXRE Expression of CYP7A1 and ABC transporters Degradate of toxic substances Via LXR /LXRE Expression of ABC transporters Endocrine production Via JAK/STAT /GHRE (growth hormone response element) IGF-1 and IGFBP-3 expression Via THR/THRE (thyroid hormone response element) Angiotensinogen expression Regenerate itself by hepatocyte mitosis Via STAT and Gab1: RAS/MAPK, PLC/IP3 and PI3K/FAK Cell growth, proliferation, survival, invasion and motility The hepatocyte also regulates other functions for constitutive synthesis of proteins (albumin, ALT and AST) that influences the synthesis or activation of other molecules (synthesis of urea and essential amino acids), activate vitamin D, utilization of vitamin K, transporter expression of vitamin A and conversion of thyroxine.