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Ketone bodies are water-soluble molecules or compounds that contain the ketone groups produced from fatty acids by the liver (ketogenesis). Ketone bodies are readily transported into tissues outside the liver, where they are converted into acetyl-CoA —which then enters the citric acid cycle and is oxidized for energy. These liver-derived ketone groups include acetoacetic acid (acetoacetate), beta-hydroxybutyrate, and acetone, a spontaneous breakdown product of acetoacetate.
Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. Physiological ketosis is a normal response to low glucose availability, such as low-carbohydrate diets or fasting, that provides an additional energy source for the brain in the form of ketones. In physiological ketosis, ketones in the blood are elevated above baseline levels, but the body's acid–base homeostasis is maintained. This contrasts with ketoacidosis, an uncontrolled production of ketones that occurs in pathologic states and causes a metabolic acidosis, which is a medical emergency. Ketoacidosis is most commonly the result of complete insulin deficiency in type 1 diabetes or late-stage type 2 diabetes. Ketone levels can be measured in blood, urine or breath and are generally between 0.5 and 3.0 millimolar (mM) in physiological ketosis, while ketoacidosis may cause blood concentrations greater than 10 mM.
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.
Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is an 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.
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.
Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.
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.
Pyruvate dehydrogenase lipoamide kinase isozyme 1, mitochondrial is an enzyme that in humans is encoded by the PDK1 gene. It codes for an isozyme of pyruvate dehydrogenase kinase (PDK).
A branched-chain amino acid (BCAA) is an amino acid having an aliphatic side-chain with a branch. Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid and alloisoleucine.
Pyruvate dehydrogenase kinase is a kinase enzyme which acts to inactivate the enzyme pyruvate dehydrogenase by phosphorylating it using ATP.
Bioenergetic systems are metabolic processes that relate to the flow of energy in living organisms. Those processes convert energy into adenosine triphosphate (ATP), which is the form suitable for muscular activity. There are two main forms of synthesis of ATP: aerobic, which uses oxygen from the bloodstream, and anaerobic, which does not. Bioenergetics is the field of biology that studies bioenergetic systems.
The Randle cycle, also known as the glucose fatty-acid cycle, is a metabolic process involving the competition of glucose and fatty acids for substrates. It is theorized to play a role in explaining type 2 diabetes and insulin resistance.
Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial (PDK4) is an enzyme that in humans is encoded by the PDK4 gene. It codes for an isozyme of pyruvate dehydrogenase kinase.
Pyruvate dehydrogenase kinase isoform 2 (PDK2) also known as pyruvate dehydrogenase lipoamide kinase isozyme 2, mitochondrial is an enzyme that in humans is encoded by the PDK2 gene. PDK2 is an isozyme of pyruvate dehydrogenase kinase.
Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.
Fructolysis refers to the metabolism of fructose from dietary sources. Though the metabolism of glucose through glycolysis uses many of the same enzymes and intermediate structures as those in fructolysis, the two sugars have very different metabolic fates in human metabolism. Unlike glucose, which is directly metabolized widely in the body, fructose is almost entirely metabolized in the liver in humans, where it is directed toward replenishment of liver glycogen and triglyceride synthesis. Under one percent of ingested fructose is directly converted to plasma triglyceride. 29% - 54% of fructose is converted in liver to glucose, and about a quarter of fructose is converted to lactate. 15% - 18% is converted to glycogen. Glucose and lactate are then used normally as energy to fuel cells all over the body.
Metabolic myopathies are myopathies that result from defects in biochemical metabolism that primarily affect muscle. They are generally genetic defects that interfere with muscle's ability to create energy, causing a low ATP reservoir within the muscle cell.
The lactate shuttle hypothesis describes the movement of lactate intracellularly and intercellularly. 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.
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.
Ketolysis is the process of catabolizing ketones, the opposite of ketogenesis which is the process of synthesizing ketones. Ketolysis provides more energy for ATP synthesis than fatty acid oxidation .
References
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- ↑ Kelley DE, Mandarino LJ (2000). "Fuel selection in human skeletal muscle in insulin resistance: a reexamination". Diabetes . 49 (2): 677–683. doi: 10.2337/diabetes.49.5.677 . PMID 10905472.
- ↑ Park S, Jeon JH, Lee IK (2018). "Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism". Diabetes Medical Journal. 42 (4): 270–281. doi:10.4093/dmj.2018.0101. PMC 6107359 . PMID 30136450.
- ↑ Thyfault JP, Morris EM (2017). "Intrinsic (Genetic) Aerobic Fitness Impacts Susceptibility for Metabolic Disease". Exercise and Sport Sciences Reviews . 45 (1): 7–15. doi:10.1249/JES.0000000000000087. PMC 5161693 . PMID 27433978.
- ↑ Cao X, Thyfault JP (2023). "Exercise drives metabolic integration between muscle, adipose and liver metabolism and protects against aging-related diseases". Experimental Gerontology . 176: 112178. doi:10.1016/j.exger.2023.112178. PMID 37085127.
- ↑ Veech RL, Bradshaw PC, King MT (2017). "Ketone bodies mimic the life span extending properties of caloric restriction". IUBMB Life . 69 (5): 305–314. doi: 10.1002/iub.1627 . PMID 28371201.
- ↑ Bradshaw PC, Seeds WA, Curtis WM (2020). "COVID-19: Proposing a Ketone-Based Metabolic Therapy as a Treatment to Blunt the Cytokine Storm". Oxidative Medicine and Cellular Longevity . 2020: 6401341. doi: 10.1155/2020/6401341 . PMC 7519203 . PMID 33014275.