Instruct: Given a question, retrieve passages that can help answer the question.
Query: How long have we known about oxidative phosphorylation?
The field of oxidative phosphorylation began with the report in 1906 by Arthur Harden of a vital role for phosphate in cellular fermentation, but initially only sugar phosphates were known to be involved. However, in the early 1940s, the link between the oxidation of sugars and the generation of ATP was firmly established by Herman Kalckar, confirming the central role of ATP in energy transfer that had been proposed by Fritz Albert Lipmann in 1941. Later, in 1949, Morris Friedkin and Albert L. Lehninger proved that the coenzyme NADH linked metabolic pathways such as the citric acid cycle and the synthesis of ATP. The term "oxidative phosphorylation" was coined by in 1939.
NADH-coenzyme Q oxidoreductase, also known as "NADH dehydrogenase" or "complex I", is the first protein in the electron transport chain. Complex I is a giant enzyme with the mammalian complex I having 46 subunits and a molecular mass of about 1,000 kilodaltons (kDa). The structure is known in detail only from a bacterium; in most organisms the complex resembles a boot with a large "ball" poking out from the membrane into the mitochondrion. The genes that encode the individual proteins are contained in both the cell nucleus and the mitochondrial genome, as is the case for many enzymes present in the mitochondrion.
In 1967, it was discovered that mitochondria contained ribosomes. In 1968, methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondrial DNA being completed in 1976.
Mitochondrial DNA was discovered in the 1960s by Margit M. K. Nass and Sylvan Nass by electron microscopy as DNase-sensitive threads inside mitochondria, and by Ellen Haslbrunner, Hans Tuppy and Gottfried Schatz by biochemical assays on highly purified mitochondrial fractions.
ERRα regulates genes involved in mitochondrial biogenesis, gluconeogenesis, oxidative phosphorylation, and fatty acid metabolism, and brown adipose tissue thermogenesis. It was recently identified as an important regulator of the mammalian circadian clock, and its output pathways at both transcriptional and physiological levels regulated the expression of transcription factors involved in metabolic homeostasis. It has been demonstrated that ERRα is required for the maintenance of diurnal cholesterol, glucose, insulin, bile acid, and trygliceride levels as well as locomotor rhythms in mice. ERRα is related to mitochondrial function but studies involving ERRα knockout mice suggested that this receptor, while dispensable for basal cellular function, is definitely necessary to provide the levels of energy necessary to respond to physiological and pathological insults in diverse tissues, the lack of that nuclear receptor leading to impaired fat metabolism and absorption.
The above figure illustrates the proposed mechanism for oxidation by the White–Chen catalyst. The reaction proceeds in conjunction with hydrogen peroxide oxidant and acetic acid. The catalyst quickly reacts with hydrogen peroxide, believed to be catalyzed by the acetic acid, and forms and iron-oxo intermediate. The iron-oxo intermediate is then thought to abstract a hydrogen on the carbon to be oxidized to generate a short-lived carbon centered radical. The iron-hydroxide then quickly rebounds onto the carbon centered radical to form the oxidized compound. Recently, direct evidence was obtained for a carbon-centered radical intermediate in this reaction using a Taxane-based radical trap. It is important to note that these reactions (both directed and non-directed) proceed with complete retention of stereochemistry, as is often observed in reactions where radical rebound is rapid enough that epimerization does not happen.
The primary structure (amino acid sequence) is highly conserved among OCP sequences, and the full-length protein is usually co-located on the chromosome with the FRP at an adjacent locus. Often, biosynthetic genes for ketocarotenoid synthesis (e.g., CrtW) are nearby. These conserved functional linkages underscore the evolutionary importance of the OCP style of photoprotection for many cyanobacteria.
Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress. The process of mitophagy was first described over a hundred years ago by Lewis and Lewis. Ashford and Porter used electron microscopy to observe mitochondrial fragments in liver lysosomes by 1962, and a 1977 report suggested that "mitochondria develop functional alterations which would activate autophagy." The term "mitophagy" was in use by 1998.
This enzyme belongs to the family of oxidoreductases, specifically those acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2 with 2-oxoglutarate as one donor, and incorporation of one atom o oxygen into each donor. The systematic name of this enzyme class is taurine, 2-oxoglutarate:O2 oxidoreductase (sulfite-forming). Other names in common use include 2-aminoethanesulfonate dioxygenase, and alpha-ketoglutarate-dependent taurine dioxygenase. This enzyme participates in taurine and hypotaurine metabolism. It has 3 cofactors: iron, Ascorbate, and Fe2+.
Christian de Duve coined the term autophagy in 1963 whereas Ohsumi began his work in 1988. Prior to that time, less than 20 papers per year were published on this subject. During the 1990s, Ohsumi's group described the morphology of autophagy in yeast, and performed mutational screening on yeast cells that identified essential genes for cells to be capable of autophagy.
5("S")-HETE may also be made in combination with 5("R")-HETE along with numerous other "(S,R)"-hydroxy polyunsaturated fatty acids as a consequence of the non-enzymatic oxidation reactions. Formation of these products can occur in any tissue subjected to oxidative stress.
The cytosolic, intermembrane space, compartment has a water content of 3.8 μl/mg protein, while the mitochondrial matrix 0.8 μl/mg protein. It is not known how mitochondria maintain osmotic balance across the inner mitochondrial membrane, although the membrane contains aquaporins that are believed to be conduits for regulated water transport. Mitochondrial matrix has a pH of about 7.8. Mitochondrial DNA was discovered by Nash and Margit in 1963. One to many double stranded mainly circular DNA is present in mitochondrial matrix. Mitochondrial DNA is 1% of total DNA of a cell. It is rich in Guanine and Cytosine content. Mitochondria of mammals have 55s ribosomes.
Organophosphates inhibit AChE, causing OP poisoning by phosphorylating the serine hydroxyl residue on AChE, which inactivates AChE. AChE is critical for nerve function, so the irreversible blockage of this enzyme, which causes acetylcholine accumulation, results in muscle overstimulation. This causes disturbances across the cholinergic synapses and can only be reactivated very slowly, if at all. Paraoxonase (PON1) is a key enzyme involved in OP pesticides and has been found to be critical in determining an organism's sensitivity to OP exposure.
The processes of oxidation and reduction occur simultaneously and cannot happen independently of one another, similar to the acid–base reaction. The oxidation alone and the reduction alone are each called a "half-reaction", because two half-reactions always occur together to form a whole reaction. When writing half-reactions, the gained or lost electrons are typically included explicitly in order that the half-reaction be balanced with respect to electric charge.
The term "biochemistry" itself is derived from a combination of biology and chemistry. In 1877, Felix Hoppe-Seyler used the term ("biochemie" in German) as a synonym for physiological chemistry in the foreword to the first issue of "Zeitschrift für Physiologische Chemie" (Journal of Physiological Chemistry) where he argued for the setting up of institutes dedicated to this field of study. The German chemist Carl Neuberg however is often cited to have coined the word in 1903, while some credited it to Franz Hofmeister.
It was once generally believed that life and its materials had some essential property or substance (often referred to as the "vital principle") distinct from any found in non-living matter, and it was thought that only living beings could produce the molecules of life. Then, in 1828, Friedrich Wöhler published a paper on the synthesis of urea, proving that organic compounds can be created artificially. Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, dual polarisation interferometry, NMR spectroscopy, radioisotopic labeling, electron microscopy, and molecular dynamics simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid cycle), and led to an understanding of biochemistry on a molecular level. Philip Randle is well-known for his discovery in diabetes research is possibly the glucose-fatty acid cycle in 1963.He confirmed that fatty acids reduce oxidation of sugar by the muscle. High fat oxidation was responsible for the insulin resistance.
The name "autophagy" was coined by Belgian biochemist Christian de Duve in 1963 based on his discovery of the functions of lysosome. The identification of autophagy-related genes in yeast in the 1990s let researchers figure out the mechanisms of autophagy, which eventually led to the award of the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yoshinori Ohsumi.
Fatty acid synthesis is an anabolic process that starts from the conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase. Malonyl CoA leads to fatty acid synthesis (FAS) and is involved in the elongation of fatty acids through Fatty acid synthase (FASN). Although aerobic glycolysis is the best documented metabolic phenotype of tumor cells, it is not a universal feature of all human cancers. Amino acids and fatty acids have been shown to function as fuels for tumor cells to proliferate. The carnitine palmitoyltransferase enzymes that regulate the β-oxidation of fatty acids may have a key role in determining some of these phenotypes. Enhanced fatty acid synthesis provides lipids for membrane biogenesis to tumor cells and hence, it gives advantage in both growth and survival of the cell.
Mutations in "FARS2" have been associated to combined oxidative phosphorylation deficiency 14, spastic paraplegia 77, and infantile-onset epilepsy and cytochrome c oxidase deficiency. Both combined oxidative phosphorylation deficiency 14 and spastic paraplegia 77 are autosomal recessive in nature and have been linked to several pathogenic variants including Y144C, I329T, D391V, and D142Y. Combined oxidative phosphorylation deficiency 14 is characterized by neonatal onset of global developmental delay, refractory seizures, lactic acidosis, and deficiencies of multiple mitochondrial respiratory enzymes. Spastic paraplegia, meanwhile, is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs, with patients often exhibiting difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. One case of infantile-onset epilepsy and cytochrome c oxidase deficiency resulting from a "FARS2" Asp325Tyr missense mutation has also been reported. Early-onset epilepsy, neurological deficits, and complex IV deficiency are the main characteristics of the disease stemming from this mutation.
The amount of oxygen in the atmosphere has fluctuated over the last 600 million years, reaching a peak of about 30% around 280 million years ago, significantly higher than today's 21%. Two main processes govern changes in the atmosphere: Plants use carbon dioxide from the atmosphere, releasing oxygen. Breakdown of pyrite and volcanic eruptions release sulfur into the atmosphere, which oxidizes and hence reduces the amount of oxygen in the atmosphere. However, volcanic eruptions also release carbon dioxide, which plants can convert to oxygen. The exact cause of the variation of the amount of oxygen in the atmosphere is not known. Periods with much oxygen in the atmosphere are associated with rapid development of animals. Today's atmosphere contains 21% oxygen, which is great enough for this rapid development of animals.
As indicated in their individual Wikipedia pages, 5-hydroxyeicosatetraenoic acid (which, like 5-oxo-eicosatetraenoic acid, acts through the OXER1 receptor), 5-oxo-eicosatetraenoic acid, 12-Hydroxyeicosatetraenoic acid, 15-Hydroxyeicosatetraenoic acid, and 20-Hydroxyeicosatetraenoic acid show numerous activities in animal and human cells as well as in animal models that are related to, for example, inflammation, allergic reactions, cancer cell growth, blood flow to tissues, and/or blood pressure. However, their function and relevancy to human physiology and pathology have not as yet been shown.
Organophosphates (also known as phosphate esters) are a class of organophosphorus compounds with the general structure O=P(OR). They can be considered as esters of phosphoric acid. Like most functional groups organophosphates occur in a diverse range of forms, with important examples including key biomolecules such as DNA, RNA and ATP, as well as many insecticides, herbicides, and nerve agents.
The main difference between eukaryotic and prokaryotic oxidative phosphorylation is that bacteria and archaea use many different substances to donate or accept electrons. This allows prokaryotes to grow under a wide variety of environmental conditions. In "E. coli", for example, oxidative phosphorylation can be driven by a large number of pairs of reducing agents and oxidizing agents, which are listed below. The midpoint potential of a chemical measures how much energy is released when it is oxidized or reduced, with reducing agents having negative potentials and oxidizing agents positive potentials.
Unlike oxidative phosphorylation, oxidation and phosphorylation are not coupled in the process of substrate-level phosphorylation, and reactive intermediates are most often gained in the course of oxidation processes in catabolism. Most ATP is generated by oxidative phosphorylation in aerobic or anaerobic respiration while substrate-level phosphorylation provides a quicker, less efficient source of ATP, independent of external electron acceptors. This is the case in human erythrocytes, which have no mitochondria, and in oxygen-depleted muscle.
In the 1960s, ATP was known to be the energy currency of life, but the mechanism by which ATP was created in the mitochondria was assumed to be by substrate-level phosphorylation. Mitchell's chemiosmotic hypothesis was the basis for understanding the actual process of oxidative phosphorylation. At the time, the biochemical mechanism of ATP synthesis by oxidative phosphorylation was unknown.
There are several well-known drugs and toxins that inhibit oxidative phosphorylation. Although any one of these toxins inhibits only one enzyme in the electron transport chain, inhibition of any step in this process will halt the rest of the process. For example, if oligomycin inhibits ATP synthase, protons cannot pass back into the mitochondrion. As a result, the proton pumps are unable to operate, as the gradient becomes too strong for them to overcome. NADH is then no longer oxidized and the citric acid cycle ceases to operate because the concentration of NAD falls below the concentration that these enzymes can use.