Mitochondrial electron transport synthesis

Iron is also a key constitnent of many enzymes involved in electron transfer reactions, inclnding those involved in the mitochondrial electron transport chain conpled to the synthesis of ATP. 

Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Since 2000 atovaquone is available as a fixed dose preparation (Malarone) with proguanil for the oral treatment of falciperum malaria. Its activity probably is based on a selective inhibiton of mitochondrial electron transport with consequent inhibition of pyrimidin synthesis. Malarone should not be used to treat severe malaria, when an injectable drug is needed. 

Mechanism of Action A systemic anti-infective that inhibits the mitochondrial electron-transport system at the cytochrome bcl complex (Complex 111), which interrupts nucleic acid and adenosine triphosphate synthesis. Therapeutic Effect Antiprotozoal and antipneumocystic activity. 

Brown Adipose Tissue Uncoupling Synthesis of ATP from Mitochondrial Electron Transport... 

Chemical reactions involving oxidation and reduction processes (redox reactions) are central to metabolism. The energy derived from the oxidation of carbohydrates is coupled to the synthesis of ATP via a series of redox reactions, the mitochondrial electron-transport chain (see Chap. 14). Moreover, most life on earth is dependent on a series of redox reactions in photosynthesis, the process in which solar energy is used to produce ATP and O2 and to synthesize carbohydrates from CO2. 

The study of bioenergetics involves the study of (1) the processes by which reduced nicotinamide and flavin nucleotides, generated primarily from the oxidation of carbohydrates (Chap. 11) and lipids (Chap. 13), are oxidized ultimately by molecular oxygen via the mitochondrial electron-transport chain, and (2) the mechanism by which this oxidation is coupled to ATP synthesis. The synthesis of ATP in this way is referred to as oxidative phosphorylation, in contrast to phosphorylation of ADP via soluble enzymes. The latter involves intermediate phosphate derivatives of the substrate and is known as substrate-level phosphorylation (Chap. 11). 

Piericidins are the first compounds obtained by the screening search for insecticidal natural products among microbial metabolites.10 They were isolated from Streptomyces mobaraensis in 1963,11 and many piericidin derivatives have been found in microbial metabolites until now.12 Piericidins are not used as insecticides practically, but are important biological reagents because they have specific inhibitory activity toward the mitochondrial electron transport chain protein nicotinamide adenine dinucleotide (NADH)-ubiquinone reductase (complex I).13 Piericidin Ax (1 in Figure 1) is biosynthesized as a polyketide,14 but genes responsible for its biosynthesis are not yet identified. Total synthesis of piericidins A (1) was reported recently.15... 

Copper plays an important role in the constituents of many enzymes of the mammalian organism as well as in plants and anthropods. Several classes of oxidizing enzymes for copper have been described, including the cytochrome oxidases which are the terminal oxidases in the mitochondrial electron transport system, a key reaction in energy metabolism (34), and the amine oxidases (35) of which there are a number that contain copper (36,37,38), Lysyl oxidase (39) is probably the most important since it plays a major role in elastin and collagen synthesis... 

Phosphine is known to disrupt protein synthesis and enzymatic activity, particularly in lung and heart cell mitochondria. This can lead to a blockage of the mitochondrial electron transport chain. Phosphine may cause denaturing of various enzymes involved in cellular respiration and metabolism, and may be responsible for denaturing of the oxyhemoglobin molecule. 

The availability of metabolites for sucrose synthesis and the need for products of sucrose degradation regulate gene expression. For respiration, sucrose is hydrolyzed by invertase to free glucose and fructose, which are phosphorylated and undergo glycolysis to pyruvate. The pyruvate is then either metabolized by mitochondrial electron transport to ATP and NADH (respiration), or metabolized to provide starting products for amino acid, lipid, and nucleotide syntheses. 

Cholesterol biosynthesis proceeds via the isoprenoids in a multistep pathway. The end product, cholesterol, and the intermediates of the pathway participate in diverse cellular functions. The isoprenoid units give rise to dolichol, CoQ, heme A, isopentenyl-tRNA, famesylated proteins, and vitamin D (in the presence of sunlight and 7-dehydrocholesterol). Dolichol is used in the synthesis of glycoproteins, CoQ in the mitochondrial electron transport chain, famesylation and geranylgeranylation by posttrans-lational lipid modification that is required for membrane association and function of proteins such as p2V and G-protein subunits. 

Protein-mediated electron transfer is a device used in a diverse array of biological transformadons. Well-known electron transfer processes include the mitochondrial electron transport system, photosynthesis (Chapter 13), and nitrogen flxadon (Chapter 15). Less well known biochemical reactions in which electron transfer plays a crucial role include nitric oxide synthesis and the cytochrome P450 electron transport systems. Each of these mechanisms is briefly oudined. 

Processes believed to be driven by mitochondrial electron transport are ATP synthesis, the pumping of calcium ions into the mitochondrial matrix, and the generation of heat by brown fat. 

Rotenone is an alkaloid botanical pesticide isolated from plants (Denis sp. or Lonchocarpus sp.). It blocks mitochondrial electron transport. It is associated with dermatitis and mucous membrane irritation in humans and is very potent in fish. In humans, intoxication is rare but when present is directed toward the respiratory system. Rotenone is used as a topical ectoparasiticide. As mentioned in the text, it has been implicated as possibly having a role in Parkinson s disease. The newest and by far safest class of insecticides available today are the insect growth inhibitors, such as methoprene (PreCor ), and chitin synthesis inhibitors, such as lufenuron (Program ). 

Atovaquone is an antiprolozoal agent (750 mg p.o. t.i.d for 21 days), that inhibits mitochondrial electron transport in metabohc enzymes of microorganisms. This may cause inhibition of nucleic acid and adenosine triphosphate synthesis. Atovaquone is indicated in the treatment of mild to moderate Pneumocystis carinii pneumonia in patients who cannot tolerate trimethoprimsulfamethoxazole, and in acute oral treatment of mild to moderate PCP in patients who are intolerant to trimethoprimsulfamethoxazole. 

Atovaquone is an antimalarial preparation. It inhibits mitochondrial electron transport in parasites, causing inhibition of nucleic acid synthesis. Proguanil exerts its effect by means of the metabolite cycloguanil, which inhibits dihydrofolate reductase in the malarial parasite, disrupting deox-ythymidylate synthesis. It is indicated in prophylaxis of P. falciparum in patients with severe renal impairment (Ccr less than 30 mL/min) hypersensitivity to any component of the product. 

FADH2 is an important carrier of electrons. FAD is the oxidized form of the molecule (lacks electrons). FADH2 is the reduced form (carries electrons). FAD and FADH2 function in many oxidation reactions, such as those catalyzed by succinate dehydrogenase and fatty acyl-CoA dehydrogenase. Electrons carried by FADH2 do not pass through complex I of the mitochondrial electron transport system and thus do not result in synthesis of as many ATPs in oxidative... 

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