The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of biochemical reactions to release the energy stored in nutrients through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The chemical energy released is available under the form of ATP. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a "cycle", it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.
Glycolysis is the metabolic pathway that converts glucose into pyruvate and, in most organisms, occurs in the liquid part of cells. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.
A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as forward reactions, and in some cases this has physiological significance: for example, alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde in animals, but in yeast it catalyzes the production of ethanol from acetaldehyde.
Pyruvic acid (IUPAC name: 2-oxopropanoic acid, also called acetoic acid) (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated as MeCHO. It is a colorless liquid or gas, boiling near room temperature. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.
Alcohol dehydrogenases (ADH) (EC 1.1.1.1) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. In humans and many other animals, they serve to break down alcohols that are otherwise toxic, and they also participate in the generation of useful aldehyde, ketone, or alcohol groups during the biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.
Acetyl-CoA is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle to be oxidized for energy production.
Digestion is the breakdown of carbohydrates to yield an energy-rich compound called ATP. The production of ATP is achieved through the oxidation of glucose molecules. In oxidation, the electrons are stripped from a glucose molecule to reduce NAD+ and FAD. NAD+ and FAD possess a high energy potential to drive the production of ATP in the electron transport chain. ATP production occurs in the mitochondria of the cell. There are two methods of producing ATP: aerobic and anaerobic. In aerobic respiration, oxygen is required. Using oxygen increases ATP production from 4 ATP molecules to about 30 ATP molecules. In anaerobic respiration, oxygen is not required. When oxygen is absent, the generation of ATP continues through fermentation. There are two types of fermentation: alcohol fermentation and lactic acid fermentation.
Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies energy to certain organs, particularly the brain, heart and skeletal muscle, under specific scenarios including fasting, caloric restriction, sleep, or others.
Acetaldehyde dehydrogenases are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetyl-CoA. This can be summarized as follows:
Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.
Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.
In biochemistry and metabolism, beta oxidation (also β-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. Acetyl-CoA enters the citric acid cycle, generating NADH and FADH2, which are electron carriers used in the electron transport chain. It is named as such because the beta carbon of the fatty acid chain undergoes oxidation and is converted to a carbonyl group to start the cycle all over again. 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.
Mitochondrial trifunctional protein deficiency is an autosomal recessive fatty acid oxidation disorder that prevents the body from converting certain fats to energy, particularly during periods without food. People with this disorder have inadequate levels of an enzyme that breaks down a certain group of fats called long-chain fatty acids.
Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes to carboxylic acids. The oxygen comes from a water molecule. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes.
Acyl-CoA is a group of coenzymes that metabolize fatty acids. Acyl-CoA's are susceptible to beta oxidation, forming, ultimately, acetyl-CoA. The acetyl-CoA enters the citric acid cycle, eventually forming several equivalents of ATP. In this way, fats are converted to ATP, the universal biochemical energy carrier.
Aldehyde dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH2 gene located on chromosome 12. ALDH2 belongs to the aldehyde dehydrogenase family of enzymes. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. ALDH2 has a low Km for acetaldehyde, and is localized in mitochondrial matrix. The other liver isozyme, ALDH1, localizes to the cytosol.
Butyryl-CoA is an organic coenzyme A-containing derivative of butyric acid. It is a natural product found in many biological pathways, such as fatty acid metabolism, fermentation, and 4-aminobutanoate (GABA) degradation. It mostly participates as an intermediate, a precursor to and converted from crotonyl-CoA. This interconversion is mediated by butyryl-CoA dehydrogenase.
Pseudohypoxia refers to a condition that mimics hypoxia, by having sufficient oxygen yet impaired mitochondrial respiration due to a deficiency of necessary co-enzymes, such as NAD+ and TPP. The increased cytosolic ratio of free NADH/NAD+ in cells (more NADH than NAD+) can be caused by diabetic hyperglycemia and by excessive alcohol consumption. Low levels of TPP results from thiamine deficiency.
The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. Mitochondria are enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver.
