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71-469: Nicotinamide adenine dinucleotide phosphate , abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions , such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form, whereas NADP is the oxidized form. NADP is used by all forms of cellular life. NADP

142-568: A chemical reaction . In a battery, an electrochemical potential arising from the movement of ions balances the reaction energy of the electrodes. The maximum voltage that a battery reaction can produce is sometimes called the standard electrochemical potential of that reaction. The generation of a transmembrane electrical potential through ion movement across a cell membrane drives biological processes like nerve conduction, muscle contraction , hormone secretion , and sensation . By convention, physiological voltages are measured relative to

213-447: A nucleotide , such as the electron carriers NAD and FAD , and coenzyme A , which carries acyl groups. Most of these cofactors are found in a huge variety of species, and some are universal to all forms of life. An exception to this wide distribution is a group of unique cofactors that evolved in methanogens , which are restricted to this group of archaea . Metabolism involves a vast array of chemical reactions, but most fall under

284-498: A proton pump . The proton pump relies on proton carriers to drive protons from the side of the membrane with a low H concentration to the side of the membrane with a high H concentration. In bacteriorhodopsin, the proton pump is activated by absorption of photons of 568nm wavelength , which leads to isomerization of the Schiff base (SB) in retinal forming the K state. This moves SB away from Asp85 and Asp212, causing H transfer from

355-513: A cofactor has been identified. Iodine is also an essential trace element, but this element is used as part of the structure of thyroid hormones rather than as an enzyme cofactor. Calcium is another special case, in that it is required as a component of the human diet, and it is needed for the full activity of many enzymes, such as nitric oxide synthase , protein phosphatases , and adenylate kinase , but calcium activates these enzymes in allosteric regulation , often binding to these enzymes in

426-453: A complex with calmodulin . Calcium is, therefore, a cell signaling molecule, and not usually considered a cofactor of the enzymes it regulates. Other organisms require additional metals as enzyme cofactors, such as vanadium in the nitrogenase of the nitrogen-fixing bacteria of the genus Azotobacter , tungsten in the aldehyde ferredoxin oxidoreductase of the thermophilic archaean Pyrococcus furiosus , and even cadmium in

497-524: A different cofactor. This process of adapting a pre-evolved structure for a novel use is known as exaptation . Prebiotic origin of coenzymes . Like amino acids and nucleotides , certain vitamins and thus coenzymes can be created under early earth conditions. For instance, vitamin B3 can be synthesized with electric discharges applied to ethylene and ammonia . Similarly, pantetheine (a vitamin B5 derivative),

568-406: A few basic types of reactions that involve the transfer of functional groups . This common chemistry allows cells to use a small set of metabolic intermediates to carry chemical groups between different reactions. These group-transfer intermediates are the loosely bound organic cofactors, often called coenzymes . Each class of group-transfer reaction is carried out by a particular cofactor, which

639-595: A fluorescence emission which peaks at 445-460 nm (violet to blue). NADP has no appreciable fluorescence. NADPH provides the reducing agents, usually hydrogen atoms, for biosynthetic reactions and the oxidation-reduction involved in protecting against the toxicity of reactive oxygen species (ROS), allowing the regeneration of glutathione (GSH). NADPH is also used for anabolic pathways, such as cholesterol synthesis , steroid synthesis, ascorbic acid synthesis, xylitol synthesis, cytosolic fatty acid synthesis and microsomal fatty acid chain elongation . The NADPH system

710-450: A fluorescent product that can be used conveniently for quantitation. Conversely, NADPH and NADH are degraded by acidic solutions while NAD/NADP are fairly stable to acid. Many enzymes that bind NADP share a common super-secondary structure named named the "Rossmann fold". The initial beta-alpha-beta (βαβ) fold is the most conserved segment of the Rossmann folds. This segment is in contact with

781-452: A form of energy storage. The gradient is usually used to drive ATP synthase, flagellar rotation, or metabolite transport. This section will focus on three processes that help establish proton gradients in their respective cells: bacteriorhodopsin and noncyclic photophosphorylation and oxidative phosphorylation. The way bacteriorhodopsin generates a proton gradient in Archaea is through

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852-435: A low-molecular-weight, non-protein organic compound that is loosely attached, participating in enzymatic reactions as a dissociable carrier of chemical groups or electrons; a prosthetic group is defined as a tightly bound, nonpolypeptide unit in a protein that is regenerated in each enzymatic turnover. Some enzymes or enzyme complexes require several cofactors. For example, the multienzyme complex pyruvate dehydrogenase at

923-446: A membrane. If there is an unequal distribution of charges across the membrane, then the difference in electric potential generates a force that drives ion diffusion until the charges are balanced on both sides of the membrane. Electrochemical gradients are essential to the operation of batteries and other electrochemical cells , photosynthesis and cellular respiration , and certain other biological processes. Electrochemical energy

994-443: A molecular mass less than 1000 Da) that can be either loosely or tightly bound to the enzyme and directly participate in the reaction. In the latter case, when it is difficult to remove without denaturing the enzyme, it can be called a prosthetic group . There is no sharp division between loosely and tightly bound cofactors. Many such as NAD can be tightly bound in some enzymes, while it is loosely bound in others. Another example

1065-406: A part of the protein sequence. This often replaces the need for an external binding factor, such as a metal ion, for protein function. Potential modifications could be oxidation of aromatic residues, binding between residues, cleavage or ring-forming. These alterations are distinct from other post-translation protein modifications , such as phosphorylation , methylation , or glycosylation in that

1136-506: A precursor of coenzyme A and thioester-dependent synthesis, can be formed spontaneously under evaporative conditions. Other coenzymes may have existed early on Earth, such as pterins (a derivative of vitamin B9 ), flavins ( FAD , flavin mononucleotide = FMN), and riboflavin (vitamin B2). Changes in coenzymes . A computational method, IPRO, recently predicted mutations that experimentally switched

1207-423: A protein at some point, and then rebind later. Both prosthetic groups and cosubstrates have the same function, which is to facilitate the reaction of enzymes and proteins. An inactive enzyme without the cofactor is called an apoenzyme , while the complete enzyme with cofactor is called a holoenzyme . The International Union of Pure and Applied Chemistry (IUPAC) defines "coenzyme" a little differently, namely as

1278-413: A source of one-carbon units to sustain nucleotide synthesis and redox homeostasis in mitochondria. Mitochondrial folate cycle has been recently suggested as the principal contributor to NADPH generation in mitochondria of cancer cells. NADPH can also be generated through pathways unrelated to carbon metabolism. The ferredoxin reductase is such an example. Nicotinamide nucleotide transhydrogenase transfers

1349-588: A structural property. Different sources give slightly different definitions of coenzymes, cofactors, and prosthetic groups. Some consider tightly bound organic molecules as prosthetic groups and not as coenzymes, while others define all non-protein organic molecules needed for enzyme activity as coenzymes, and classify those that are tightly bound as coenzyme prosthetic groups. These terms are often used loosely. A 1980 letter in Trends in Biochemistry Sciences noted

1420-422: A subsequent reaction catalyzed by a different enzyme. In the latter case, the cofactor can also be considered a substrate or cosubstrate. Vitamins can serve as precursors to many organic cofactors (e.g., vitamins B 1 , B 2 , B 6 , B 12 , niacin , folic acid ) or as coenzymes themselves (e.g., vitamin C ). However, vitamins do have other functions in the body. Many organic cofactors also contain

1491-418: Is thiamine pyrophosphate (TPP), which is tightly bound in transketolase or pyruvate decarboxylase , while it is less tightly bound in pyruvate dehydrogenase . Other coenzymes, flavin adenine dinucleotide (FAD), biotin , and lipoamide , for instance, are tightly bound. Tightly bound cofactors are, in general, regenerated during the same reaction cycle, while loosely bound cofactors can be regenerated in

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1562-432: Is a gradient of electrochemical potential , usually for an ion that can move across a membrane . The gradient consists of two parts: When there are unequal concentrations of an ion across a permeable membrane, the ion will move across the membrane from the area of higher concentration to the area of lower concentration through simple diffusion . Ions also carry an electric charge that forms an electric potential across

1633-422: Is also responsible for generating free radicals in immune cells by NADPH oxidase . These radicals are used to destroy pathogens in a process termed the respiratory burst . It is the source of reducing equivalents for cytochrome P450 hydroxylation of aromatic compounds , steroids , alcohols , and drugs . NADH and NADPH are very stable in basic solutions, but NAD and NADP are degraded in basic solutions into

1704-563: Is conducted using X-ray crystallography and mass spectroscopy ; structural data is necessary because sequencing does not readily identify the altered sites. The term is used in other areas of biology to refer more broadly to non-protein (or even protein) molecules that either activate, inhibit, or are required for the protein to function. For example, ligands such as hormones that bind to and activate receptor proteins are termed cofactors or coactivators, whereas molecules that inhibit receptor proteins are termed corepressors. One such example

1775-406: Is essential for life because it is needed for cellular respiration. NADP differs from NAD by the presence of an additional phosphate group on the 2' position of the ribose ring that carries the adenine moiety . This extra phosphate is added by NAD kinase and removed by NADP phosphatase. In general, NADP is synthesized before NADPH is. Such a reaction usually starts with NAD from either

1846-441: Is one of the many interchangeable forms of potential energy through which energy may be conserved . It appears in electroanalytical chemistry and has industrial applications such as batteries and fuel cells. In biology, electrochemical gradients allow cells to control the direction ions move across membranes. In mitochondria and chloroplasts , proton gradients generate a chemiosmotic potential used to synthesize ATP , and

1917-753: Is released from PSII after gaining two protons from the stroma. The electrons in P 680 are replenished by oxidizing water through the oxygen-evolving complex (OEC). This results in release of O 2 and H into the lumen, for a total reaction of 4 h ν + 2 H 2 O + 2 PQ + 4 H + ( stroma ) ⟶ O 2 + 2 PQH 2 + 4 H + ( lumen ) {\displaystyle 4h\nu +2{\ce {H2O}}+2{\ce {PQ}}+4{\ce {H+}}({\text{stroma}})\longrightarrow {\ce {O2}}+2{\ce {PQH2}}+4{\ce {H+}}({\text{lumen}})} After being released from PSII, PQH 2 travels to

1988-434: Is the G protein-coupled receptor family of receptors, which are frequently found in sensory neurons. Ligand binding to the receptors activates the G protein, which then activates an enzyme to activate the effector. In order to avoid confusion, it has been suggested that such proteins that have ligand-binding mediated activation or repression be referred to as coregulators. Proton gradient An electrochemical gradient

2059-542: Is the substrate for a set of enzymes that produce it, and a set of enzymes that consume it. An example of this are the dehydrogenases that use nicotinamide adenine dinucleotide (NAD ) as a cofactor. Here, hundreds of separate types of enzymes remove electrons from their substrates and reduce NAD to NADH. This reduced cofactor is then a substrate for any of the reductases in the cell that require electrons to reduce their substrates. Therefore, these cofactors are continuously recycled as part of metabolism . As an example,

2130-404: Is transferred to heme b L which then transfers it to heme b H which then transfers it to PQ. In the second reaction, a second PQH 2 gets oxidized, adding an electron to another plastocyanin and PQ. Both reactions together transfer four protons into the lumen. In the electron transport chain, complex I (CI) catalyzes the reduction of ubiquinone (UQ) to ubiquinol (UQH 2 ) by

2201-503: The Entner–Doudoroff pathway , but NADPH production remains the same. Ferredoxin–NADP reductase , present in all domains of life, is a major source of NADPH in photosynthetic organisms including plants and cyanobacteria. It appears in the last step of the electron chain of the light reactions of photosynthesis . It is used as reducing power for the biosynthetic reactions in the Calvin cycle to assimilate carbon dioxide and help turn

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2272-989: The Q-cycle . The first step involving the transfer of two electrons from the UQH 2 reduced by CI to two molecules of oxidized cytochrome c at the Q o site. In the second step, two more electrons reduce UQ to UQH 2 at the Q i site. The total reaction is: 2 cytochrome c ⏟ oxidized + UQH 2 + 2 H + ⏟ matrix ⟶ 2 cytochrome c ⏟ reduced + UQ + 4 H + ⏟ IMS {\displaystyle 2\underbrace {\text{cytochrome c}} _{\text{oxidized}}+{\ce {UQH_2}}+2\underbrace {{\ce {H^+}}} _{\text{matrix}}\longrightarrow 2\underbrace {\text{cytochrome c}} _{\text{reduced}}+{\ce {UQ}}+4\underbrace {{\ce {H^+}}} _{\text{IMS}}} Complex IV (CIV) catalyzes

2343-559: The carbonic anhydrase from the marine diatom Thalassiosira weissflogii . In many cases, the cofactor includes both an inorganic and organic component. One diverse set of examples is the heme proteins, which consist of a porphyrin ring coordinated to iron . Iron–sulfur clusters are complexes of iron and sulfur atoms held within proteins by cysteinyl residues. They play both structural and functional roles, including electron transfer, redox sensing, and as structural modules. Organic cofactors are small organic molecules (typically

2414-563: The cytochrome b 6 f complex , which then transfers two electrons from PQH 2 to plastocyanin in two separate reactions. The process that occurs is similar to the Q-cycle in Complex III of the electron transport chain. In the first reaction, PQH 2 binds to the complex on the lumen side and one electron is transferred to the iron-sulfur center which then transfers it to cytochrome f which then transfers it to plastocyanin. The second electron

2485-495: The gas constant , T represents absolute temperature , z is the charge per ion, and F represents the Faraday constant . In the example of Na , both terms tend to support transport: the negative electric potential inside the cell attracts the positive ion and since Na is concentrated outside the cell, osmosis supports diffusion through the Na channel into the cell. In the case of K ,

2556-561: The last universal ancestor , which lived about 4 billion years ago. Organic cofactors may have been present even earlier in the history of life on Earth. The nucleotide adenosine is a cofactor for many basic metabolic enzymes such as transferases. It may be a remnant of the RNA world . Adenosine-based cofactors may have acted as adaptors that allowed enzymes and ribozymes to bind new cofactors through small modifications in existing adenosine-binding domains , which had originally evolved to bind

2627-495: The matrix to the intermembrane space (IMS); for every electron pair entering the chain, ten protons translocate into the IMS. The result is an electric potential of more than 200 mV . The energy resulting from the flux of protons back into the matrix is used by ATP synthase to combine inorganic phosphate and ADP . Similar to the electron transport chain, the light-dependent reactions of photosynthesis pump protons into

2698-453: The molar Gibbs free energy change associated with successful transport is Δ G = R T ln ⁡ ( c i n c o u t ) + ( F z ) V m e m b r a n e {\displaystyle \Delta G=RT\ln {\!\left({\frac {c_{\rm {in}}}{c_{\rm {out}}}}\right)}+(Fz)V_{\rm {membrane}}} where R represents

2769-615: The nucleotide adenosine monophosphate (AMP) as part of their structures, such as ATP , coenzyme A , FAD , and NAD . This common structure may reflect a common evolutionary origin as part of ribozymes in an ancient RNA world . It has been suggested that the AMP part of the molecule can be considered to be a kind of "handle" by which the enzyme can "grasp" the coenzyme to switch it between different catalytic centers. Cofactors can be divided into two major groups: organic cofactors , such as flavin or heme ; and inorganic cofactors , such as

2840-436: The sodium-potassium gradient helps neural synapses quickly transmit information. An electrochemical gradient has two components: a differential concentration of electric charge across a membrane and a differential concentration of chemical species across that same membrane. In the former effect, the concentrated charge attracts charges of the opposite sign; in the latter, the concentrated species tends to diffuse across

2911-432: The thylakoid lumen of chloroplasts to drive the synthesis of ATP. The proton gradient can be generated through either noncyclic or cyclic photophosphorylation. Of the proteins that participate in noncyclic photophosphorylation, photosystem II (PSII), plastiquinone , and cytochrome b 6 f complex directly contribute to generating the proton gradient. For each four photons absorbed by PSII, eight protons are pumped into

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2982-795: The ADP portion of NADP. Therefore, it is also called an "ADP-binding βαβ fold". In 2018 and 2019, the first two reports of enzymes that catalyze the removal of the 2' phosphate of NADP(H) in eukaryotes emerged. First the cytoplasmic protein MESH1 ( Q8N4P3 ), then the mitochondrial protein nocturnin were reported. Of note, the structures and NADPH binding of MESH1 ( 5VXA ) and nocturnin ( 6NF0 ) are not related. Cofactor (biochemistry) Cofactors can be classified into two types: inorganic ions and complex organic molecules called coenzymes . Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. (Some scientists limit

3053-586: The SB to Asp85 forming the M1 state. The protein then shifts to the M2 state by separating Glu204 from Glu194 which releases a proton from Glu204 into the external medium. The SB is reprotonated by Asp96 which forms the N state. It is important that the second proton comes from Asp96 since its deprotonated state is unstable and rapidly reprotonated with a proton from the cytosol . The protonation of Asp85 and Asp96 causes re-isomerization of

3124-411: The SB, forming the O state. Finally, bacteriorhodopsin returns to its resting state when Asp85 releases its proton to Glu204. PSII also relies on light to drive the formation of proton gradients in chloroplasts, however, PSII utilizes vectorial redox chemistry to achieve this goal. Rather than physically transporting protons through the protein, reactions requiring the binding of protons will occur on

3195-524: The amino acids typically acquire new functions. This increases the functionality of the protein; unmodified amino acids are typically limited to acid-base reactions, and the alteration of resides can give the protein electrophilic sites or the ability to stabilize free radicals. Examples of cofactor production include tryptophan tryptophylquinone (TTQ), derived from two tryptophan side chains, and 4-methylidene-imidazole-5-one (MIO), derived from an Ala-Ser-Gly motif. Characterization of protein-derived cofactors

3266-586: The author could not arrive at a single all-encompassing definition of a "coenzyme" and proposed that this term be dropped from use in the literature. Metal ions are common cofactors. The study of these cofactors falls under the area of bioinorganic chemistry . In nutrition , the list of essential trace elements reflects their role as cofactors. In humans this list commonly includes iron , magnesium , manganese , cobalt , copper , zinc , and molybdenum . Although chromium deficiency causes impaired glucose tolerance , no human enzyme that uses this metal as

3337-688: The carbon dioxide into glucose. It has functions in accepting electrons in other non-photosynthetic pathways as well: it is needed in the reduction of nitrate into ammonia for plant assimilation in nitrogen cycle and in the production of oils. There are several other lesser-known mechanisms of generating NADPH, all of which depend on the presence of mitochondria in eukaryotes. The key enzymes in these carbon-metabolism-related processes are NADP-linked isoforms of malic enzyme , isocitrate dehydrogenase (IDH), and glutamate dehydrogenase . In these reactions, NADP acts like NAD in other enzymes as an oxidizing agent. The isocitrate dehydrogenase mechanism appears to be

3408-440: The cell. This makes the inside of the cell more negative than the outside and more specifically generates a membrane potential V membrane of about −60 mV . An example of passive transport is ion fluxes through Na , K , Ca , and Cl channels. Unlike active transport, passive transport is powered by the arithmetic sum of osmosis (a concentration gradient) and an electric field (the transmembrane potential). Formally,

3479-550: The cofactor specificity of Candida boidinii xylose reductase from NADPH to NADH. Evolution of enzymes without coenzymes . If enzymes require a co-enzyme, how does the coenzyme evolve? The most likely scenario is that enzymes can function initially without their coenzymes and later recruit the coenzyme, even if the catalyzed reaction may not be as efficient or as fast. Examples are Alcohol Dehydrogenase (coenzyme: NAD⁺ ), Lactate Dehydrogenase (NAD⁺), Glutathione Reductase ( NADPH ). The first organic cofactor to be discovered

3550-415: The confusion in the literature and the essentially arbitrary distinction made between prosthetic groups and coenzymes group and proposed the following scheme. Here, cofactors were defined as an additional substance apart from protein and substrate that is required for enzyme activity and a prosthetic group as a substance that undergoes its whole catalytic cycle attached to a single enzyme molecule. However,

3621-420: The course of the day. This means that each ATP molecule is recycled 1000 to 1500 times daily. Organic cofactors, such as ATP and NADH , are present in all known forms of life and form a core part of metabolism . Such universal conservation indicates that these molecules evolved very early in the development of living things. At least some of the current set of cofactors may, therefore, have been present in

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3692-473: The de-novo or the salvage pathway, with NAD kinase adding the extra phosphate group. ADP-ribosyl cyclase allows for synthesis from nicotinamide in the salvage pathway, and NADP phosphatase can convert NADPH back to NADH to maintain a balance. Some forms of the NAD kinase, notably the one in mitochondria, can also accept NADH to turn it directly into NADPH. The prokaryotic pathway is less well understood, but with all

3763-407: The early 20th century, with ATP being isolated in 1929 by Karl Lohmann, and coenzyme A being discovered in 1945 by Fritz Albert Lipmann . The functions of these molecules were at first mysterious, but, in 1936, Otto Heinrich Warburg identified the function of NAD in hydride transfer. This discovery was followed in the early 1940s by the work of Herman Kalckar , who established the link between

3834-500: The effect of osmosis is reversed: although external ions are attracted by the negative intracellular potential, entropy seeks to diffuse the ions already concentrated inside the cell. The converse phenomenon (osmosis supports transport, electric potential opposes it) can be achieved for Na in cells with abnormal transmembrane potentials: at +70 mV , the Na influx halts; at higher potentials, it becomes an efflux. Proton gradients in particular are important in many types of cells as

3905-413: The extracellular region; a typical animal cell has an internal electrical potential of (−70)–(−50) mV. An electrochemical gradient is essential to mitochondrial oxidative phosphorylation . The final step of cellular respiration is the electron transport chain , composed of four complexes embedded in the inner mitochondrial membrane. Complexes I, III, and IV pump protons from

3976-425: The extracellular side while reactions requiring the release of protons will occur on the intracellular side. Absorption of photons of 680nm wavelength is used to excite two electrons in P 680 to a higher energy level . These higher energy electrons are transferred to protein-bound plastoquinone (PQ A ) and then to unbound plastoquinone (PQ B ). This reduces plastoquinone (PQ) to plastoquinol (PQH 2 ) which

4047-440: The hydrogen between NAD(P)H and NAD(P), and is found in eukaryotic mitochondria and many bacteria. There are versions that depend on a proton gradient to work and ones that do not. Some anaerobic organisms use NADP-linked hydrogenase , ripping a hydride from hydrogen gas to produce a proton and NADPH. Like NADH , NADPH is fluorescent . NADPH in aqueous solution excited at the nicotinamide absorbance of ~335 nm (near UV) has

4118-409: The ions that pass through the membrane correspond to water traveling into the lower river. Conversely, energy can be used to pump water up into the lake above the dam , and chemical energy can be used to create electrochemical gradients. The term typically applies in electrochemistry , when electrical energy in the form of an applied voltage is used to modulate the thermodynamic favorability of

4189-404: The junction of glycolysis and the citric acid cycle requires five organic cofactors and one metal ion: loosely bound thiamine pyrophosphate (TPP), covalently bound lipoamide and flavin adenine dinucleotide (FAD), cosubstrates nicotinamide adenine dinucleotide (NAD ) and coenzyme A (CoA), and a metal ion (Mg ). Organic cofactors are often vitamins or made from vitamins. Many contain

4260-409: The lumen. Several other transporters and ion channels play a role in generating a proton electrochemical gradient. One is TPK 3 , a potassium channel that is activated by Ca and conducts K from the thylakoid lumen to the stroma , which helps establish the electric field . On the other hand, the electro-neutral K efflux antiporter (KEA 3 ) transports K into the thylakoid lumen and H into

4331-446: The major source of NADPH in fat and possibly also liver cells. These processes are also found in bacteria. Bacteria can also use a NADP-dependent glyceraldehyde 3-phosphate dehydrogenase for the same purpose. Like the pentose phosphate pathway, these pathways are related to parts of glycolysis . Another carbon metabolism-related pathway involved in the generation of NADPH is the mitochondrial folate cycle, which uses principally serine as

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4402-714: The membrane to an equalize concentrations. The combination of these two phenomena determines the thermodynamically-preferred direction for an ion 's movement across the membrane. The combined effect can be quantified as a gradient in the thermodynamic electrochemical potential : ∇ μ ¯ i = ∇ μ i ( r → ) + z i F ∇ φ ( r → ) , {\displaystyle \nabla {\overline {\mu }}_{i}=\nabla \mu _{i}({\vec {r}})+z_{i}\mathrm {F} \nabla \varphi ({\vec {r}}){\text{,}}} with Sometimes,

4473-399: The metal ions Mg , Cu , Mn and iron–sulfur clusters . Organic cofactors are sometimes further divided into coenzymes and prosthetic groups . The term coenzyme refers specifically to enzymes and, as such, to the functional properties of a protein. On the other hand, "prosthetic group" emphasizes the nature of the binding of a cofactor to a protein (tight or covalent) and, thus, refers to

4544-433: The oxidation of sugars and the generation of ATP. This confirmed 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 NAD linked metabolic pathways such as the citric acid cycle and the synthesis of ATP. In a number of enzymes, the moiety that acts as a cofactor is formed by post-translational modification of

4615-406: The similar proteins the process should work in a similar way. NADPH is produced from NADP. The major source of NADPH in animals and other non-photosynthetic organisms is the pentose phosphate pathway , by glucose-6-phosphate dehydrogenase (G6PDH) in the first step. The pentose phosphate pathway also produces pentose, another important part of NAD(P)H, from glucose. Some bacteria also use G6PDH for

4686-552: The stroma, which helps establish the pH gradient. Since the ions are charged, they cannot pass through cellular membranes via simple diffusion. Two different mechanisms can transport the ions across the membrane: active or passive transport. An example of active transport of ions is the Na -K -ATPase (NKA). NKA is powered by the hydrolysis of ATP into ADP and an inorganic phosphate; for every molecule of ATP hydrolized, three Na are transported outside and two K are transported inside

4757-442: The term "electrochemical potential" is abused to describe the electric potential generated by an ionic concentration gradient; that is, φ . An electrochemical gradient is analogous to the water pressure across a hydroelectric dam . Routes unblocked by the membrane (e.g. membrane transport protein or electrodes ) correspond to turbines that convert the water's potential energy to other forms of physical or chemical energy, and

4828-431: The total quantity of ATP in the human body is about 0.1  mole . This ATP is constantly being broken down into ADP, and then converted back into ATP. Thus, at any given time, the total amount of ATP + ADP remains fairly constant. The energy used by human cells requires the hydrolysis of 100 to 150 moles of ATP daily, which is around 50 to 75 kg. In typical situations, humans use up their body weight of ATP over

4899-758: The transfer of two electrons from reduced nicotinamide adenine dinucleotide (NADH) which translocates four protons from the mitochondrial matrix to the IMS: NADH + H + + UQ + 4 H + ⏟ m a t r i x ⟶ NAD + + UQH 2 + 4 H + ⏟ I M S {\displaystyle {\ce {NADH}}+{\ce {H^+}}+{\ce {UQ}}+4\underbrace {{\ce {H^+}}} _{\mathrm {matrix} }\longrightarrow {\ce {NAD^+}}+{\ce {UQH_2}}+4\underbrace {{\ce {H^+}}} _{\mathrm {IMS} }} Complex III (CIII) catalyzes

4970-416: The use of the term "cofactor" for inorganic substances; both types are included here. ) Coenzymes are further divided into two types. The first is called a " prosthetic group ", which consists of a coenzyme that is tightly (or even covalently) and permanently bound to a protein. The second type of coenzymes are called "cosubstrates", and are transiently bound to the protein. Cosubstrates may be released from

5041-496: Was NAD , which was identified by Arthur Harden and William Young 1906. They noticed that adding boiled and filtered yeast extract greatly accelerated alcoholic fermentation in unboiled yeast extracts. They called the unidentified factor responsible for this effect a coferment . Through a long and difficult purification from yeast extracts, this heat-stable factor was identified as a nucleotide sugar phosphate by Hans von Euler-Chelpin . Other cofactors were identified throughout

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