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Lactate Shuttle Hypothesis
The lactate shuttle hypothesis describes the movement of lactate intracellularly (within a cell) and intercellularly (between cells). The hypothesis is based on the observation that lactate is formed and utilized continuously in diverse cells under both anaerobic and aerobic conditions. Further, lactate produced at sites with high rates of glycolysis and glycogenolysis can be shuttled to adjacent or remote sites including heart or skeletal muscles where the lactate can be used as a gluconeogenic precursor or substrate for oxidation. The hypothesis was proposed by professor George Brooks of the University of California at Berkeley. In addition to its role as a fuel source predominantly in the muscles, heart, brain, and liver, the lactate shuttle hypothesis also relates the role of lactate in redox signalling, gene expression, and lipolytic control. These additional roles of lactate have given rise to the term ‘lactormone’, pertaining to the role of lactate as a signalling h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lactic Acid
Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natural sources. Lactic acid is an alpha-hydroxy acid (AHA) due to the presence of a hydroxyl group adjacent to the carboxyl group. It is used as a synthetic intermediate in many organic synthesis industries and in various biochemical industries. The conjugate base of lactic acid is called lactate (or the lactate anion). The name of the derived acyl group is lactoyl. In solution, it can ionize by loss of a proton to produce the lactate ion . Compared to acetic acid, its p''K'' is 1 unit less, meaning lactic acid is ten times more acidic than acetic acid. This higher acidity is the consequence of the intramolecular hydrogen bonding between the α-hydroxyl and the carboxylate group. Lactic acid is chiral, consisting of two enantiomers. One ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
β-oxidation
In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, and NADH and FADH2, which are co-enzymes used in the electron transport chain. It is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes. The overall reaction for one cycle of beta oxidation is: :C''n''-acyl-CoA + FAD + + + CoA → C''n''-2-acyl-CoA + + NADH + + acetyl-CoA Activation and membrane transport Free fatty acids cannot penetrate any biological membrane due to their negative charge. Free fatty acids must cross the cell membrane through specific transport proteins ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cancer Research
Cancer research is research into cancer to identify causes and develop strategies for prevention, diagnosis, treatment, and cure. Cancer research ranges from epidemiology, molecular bioscience to the performance of clinical trials to evaluate and compare applications of the various cancer treatments. These applications include surgery, radiation therapy, chemotherapy, hormone therapy, immunotherapy and combined treatment modalities such as chemo-radiotherapy. Starting in the mid-1990s, the emphasis in clinical cancer research shifted towards therapies derived from biotechnology research, such as cancer immunotherapy and gene therapy. Cancer research is done in academia, research institutes, and corporate environments, and is largely government funded. History Cancer research has been ongoing for centuries. Early research focused on the causes of cancer. Percivall Pott identified the first environmental trigger (chimney soot) for cancer in 1775 and cigarette smoking was identif ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HIF-1
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals. Discovery The HIF transcriptional complex was discovered in 1995 by Gregg L. Semenza and postdoctoral fellow Guang Wang. In 2016, William Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza were presented the Lasker Award for their work in elucidating the role of HIF-1 in oxygen sensing and its role in surviving low oxygen conditions. In 2019, the same three individuals were jointly awarded the Nobel Prize in Physiology or Medicine for their work in elucidating how HIF senses and adapts cellular response to oxygen availability. Structure Most, if not all, oxygen-breathing species express the highly conserved transcriptional complex HIF-1, which is a heterodimer composed of an alpha and a beta subunit, the latter being a constitutively-expressed aryl hydrocarbon receptor nucl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise (especially in older texts). The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease. Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. However, it is also a fundamental step in the transition of tumors from a benign state to a malignant one, leading to the use of angiogenesis inhibitors in the treatment of cancer. The essential role of angiogenesis in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Warburg Effect (oncology)
In oncology, the Warburg effect () is the observation that most cancer cells produce energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear. In fermentation, the last product of glycolysis, pyruvate, is converted into lactate (lactic acid fermentation) or ethanol (alcoholic fermentation). While fermentation produces adenosine triphosphate (ATP) only in low yield co ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen ( glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise. In humans, substrates for gluconeogenesis may come from any non-carbohydrate sources that can be converted to pyruvate or intermediates ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GPR81
Hydroxycarboxylic acid receptor 1 (HCA1), formerly known as G protein-coupled receptor 81 (GPR81), is a protein that in humans is encoded by the ''HCAR1'' gene. HCA1, like the other hydroxycarboxylic acid receptors HCA2 and HCA3, is a G protein-coupled receptor (GPCR). The primary endogenous agonist of HCA1 is lactic acid (and its conjugate base, lactate). Lactate activates HCA1, which in turn inhibits lipolysis in fat cell Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...s. References Further reading * * * G protein-coupled receptors {{gene-12-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Peroxisome Proliferator-activated Receptor Gamma
Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the ''PPARG'' gene. Tissue distribution PPARG is mainly present in adipose tissue, colon and macrophages. Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine). Gene expression This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte di ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cytochrome C Oxidase
The enzyme cytochrome c oxidase or Complex IV, (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and mitochondria of eukaryotes. It is the last enzyme in the respiratory electron transport chain of cells located in the membrane. It receives an electron from each of four cytochrome c molecules and transfers them to one oxygen molecule and four protons, producing two molecules of water. In addition to binding the four protons from the inner aqueous phase, it transports another four protons across the membrane, increasing the transmembrane difference of proton electrochemical potential, which the ATP synthase then uses to synthesize ATP. Structure The complex The complex is a large integral membrane protein composed of several metal prosthetic sites and 14 protein subunits in mammals. In mammals, eleven subunits are nuclear in origin, and three are synthesized in the mitochondria. The complex contains two ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Isoenzyme
In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. different ''K''M values), or are regulated differently. They permit the fine-tuning of metabolism to meet the particular needs of a given tissue or developmental stage. In many cases, isozymes are encoded by homologous genes that have diverged over time. Strictly speaking, enzymes with different amino acid sequences that catalyse the same reaction are isozymes if encoded by different genes, or allozymes if encoded by different alleles of the same gene; the two terms are often used interchangeably. Introduction Isozymes were first described by R. L. Hunter and Clement Markert (1957) who defined them as ''different variants of the same enzyme having identical functions and present in the same individual''. This definition encompasses (1) ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fermentation
Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food production, it may more broadly refer to any process in which the activity of microorganisms brings about a desirable change to a foodstuff or beverage. The science of fermentation is known as zymology. In microorganisms, fermentation is the primary means of producing adenosine triphosphate (ATP) by the degradation of organic nutrients anaerobically. Humans have used fermentation to produce foodstuffs and beverages since the Neolithic age. For example, fermentation is used for preservation in a process that produces lactic acid found in such sour foods as pickled cucumbers, kombucha, kimchi, and yogurt, as well as for producing alcoholic beverages such as wine and beer. Fermentation also occurs within the gastrointestinal tracts of all a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
