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Gluconeogenesis pathway with key molecules and enzymes. Many steps are the opposite of those found in the glycolysis.
Gluconeogenesis pathway with key molecules and enzymes. Many steps are the opposite of those found in the glycolysis. See also Gluconeogenesis, which carries out a process wherein glucose is synthesized rather than catabolized

Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids. In Biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Carbohydrates (from ' Hydrates of Carbon ' or saccharides ( Greek σάκχαρον meaning " Sugar " are the most Pyruvic acid (CH3COCO2H is an alpha-keto acid. The Carboxylate Anion of pyruvic acid is known as pyruvate. Lactic acid ( IUPAC Systematic name: 2-hydroxypropanoic acid) also known as milk acid, is a Chemical compound that plays a role A glucogenic amino acid is an Amino acid that can be converted into Glucose through Gluconeogenesis.

The vast majority of gluconeogenesis takes place in the liver and, to a smaller extent, in the cortex of kidneys. The liver is a vital organ in the human body and is present in Vertebrates and some other animals The kidneys are complicated organs that have numerous biological roles This process occurs during periods of fasting, starvation, or intense exercise and is highly endergonic. Fasting is primarily the act of willingly abstaining from some or all Food, Drink, or both for a period of time Starvation (also called inanition) is a severe reduction in Vitamin, Nutrient, and Energy intake and is the most extreme form of Endergonic means absorbing energy in the form of work Its etymology stems from the suffix -ergonic as derived from the Greek root ergon meaning work, Gluconeogenesis is often associated with ketosis. Ketosis (kiːˈtoʊsɪs is a state in Metabolism occurring when the Liver excessively converts fat into fatty acids and Ketone Gluconeogenesis is also a target of therapy for type II diabetes, such as metformin, which inhibit glucose formation and stimulate glucose uptake by cells. Metformin ( INN; trade names Glucophage, Riomet, Fortamet, Glumetza, Obimet, Dianben, Diabex, [1]

Contents

Entering the pathway

Several non-carbohydrate carbon substrates can enter the gluconeogenesis pathway. Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 In Biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. One common substrate is lactic acid, formed during anaerobic respiration in skeletal muscle. Lactic acid ( IUPAC Systematic name: 2-hydroxypropanoic acid) also known as milk acid, is a Chemical compound that plays a role See also Fermentation (biochemistry Anaerobic respiration (anaerobiosis refers to the Oxidation of molecules in the absence of Oxygen to produce Lactate is transported back to the liver where it is converted into pyruvate by the Cori cycle using the enzyme lactate dehydrogenase. Pyruvic acid (CH3COCO2H is an alpha-keto acid. The Carboxylate Anion of pyruvic acid is known as pyruvate. The Cori cycle, named after its discoverers Carl Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic Glycolysis Lactate dehydrogenase ( LDH) is an Enzyme ( present in a wide variety of organisms including plants and animals Pyruvate, the first designated substrate of the gluconeogenic pathway, can then be used to generate glucose. [2]

All citric acid cycle intermediates, through conversion to oxaloacetate, amino acids other than lysine or leucine, and glycerol can also function as substrates for gluconeogenesis. The citric acid cycle, also known as the tricarboxylic acid cycle ( TCA cycle) or the Krebs cycle, (or rarely the Szent-Györgyi–Krebs cycle Oxaloacetic acid is an Organic compound with the chemical formula HO2CC(OCH2CO2H In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Lysine (abbreviated as Lys or K) is an α- Amino acid with the Chemical formula HO2CCH(NH2(CH24NH2 Leucine (abbreviated as Leu or L) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH2CH(CH32 [3] Amino acids must have their amino group removed by transamination or deamination before entering the cycle directly (as pyruvate or oxaloacetate), or indirectly via the citric acid cycle. There are two chemical reactions known as transamination (or aminotransfer Deamination is the removal of an Amine group from a Molecule.

Fatty acids cannot be converted into glucose in animals, the exception being odd-chain fatty acids which yield propionyl CoA, a precursor for succinyl CoA. In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which Propionyl-CoA is a Coenzyme A derivative of Propionic acid. Metabolism in animals Production There are several different ways in which Succinyl-Coenzyme A, generally abbreviated as Succinyl-CoA or SucCoA is a combination of Succinic acid and Coenzyme A. In plants, specifically in seedlings, the glyoxylate cycle can be used to convert fatty acids (acetate) into the primary carbon source of the organism. The glyoxylate cycle is a Metabolic pathway occurring in Plants certain Vertebrates and several Microorganisms such as E An acetate, or ethanoate, is either a salt or Ester of Acetic acid. The glyoxylate cycle produces four-carbon dicarboxylic acids that can enter gluconeogenesis. [4] Glycerol, which is a part of all triacylglycerols, can also be used in gluconeogenesis. (more properly known as, TAG or triacylglyceride) is Glyceride in which the Glycerol is Esterified with three Fatty acids It is the In organisms in which glycerol is derived from glucose (e. g. , humans and other mammals), glycerol is sometimes not considered a true gluconeogenic substrate, as it cannot be used to generate new glucose.

Pathway

Gluconeogenesis is a pathway consisting of eleven enzyme-catalyzed reactions. The pathway can begin in the mitochondria or cytoplasm, depending on the substrate being used. Many of the reactions are reversible steps found in glycolysis.

Regulation

While most steps in gluconeogenesis are the reverse of those found in glycolysis, three regulated and strongly exergonic reactions are replaced with more kinetically favorable reactions. See also Gluconeogenesis, which carries out a process wherein glucose is synthesized rather than catabolized Hexokinase/glucokinase, phosphofructokinase, and pyruvate kinase enzymes of glycolysis are replaced with glucose-6-phosphatase, fructose-1,6-bisphosphatase, and PEP carboxykinase. This system of reciprocal control allow glycolysis and gluconeogenesis to inhibit each other and prevent the formation of a futile cycle. A Futile cycle is when two Metabolic pathways run simultaneously in opposite directions and have no overall effect other than wasting energy

The majority of the enzymes responsible for gluconeogenesis are found in the cytoplasm; the exceptions are mitochondrial pyruvate carboxylase, and, in animals, phosphoenolpyruvate carboxykinase. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. Pyruvate carboxylase is an Enzyme of the Ligase class that Catalyzes the irreversible Carboxylation of Pyruvate to form Oxaloacetate Not to be confused with Phosphoenolpyruvate carboxylase, PEPC Phosphoenolpyruvate carboxykinase (or PEPCK) is an Enzyme The latter exists as an isozyme located in both the mitochondrion and the cytosol. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. [5] As there is no known mechanism to transport phosphoenolpyruvate from the mitochondrion into the cytosol, the cytosolic enzyme is believed to be the isozyme important for gluconeogenesis. Phosphoenolpyruvate (synonyms phosphoenolpyruvic acid, PEP) is an important Chemical compound in Biochemistry. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. The rate of gluconeogenesis is ultimately controlled by the action of a key enzyme, fructose-1,6-bisphosphatase, which is also regulated through signal tranduction by cAMP and its phosphorylation. Fructose bisphosphatase ( is an Enzyme in the Liver, that converts Fructose-16-bisphosphate to Fructose-6-phosphate in Gluconeogenesis

Most factors that regulate the activity of the gluconeogenesis pathway do so by inhibiting the activity or expression of key enzymes. However, both acetyl CoA and citrate activate gluconeogenesis enzymes (pyruvate carboxylase and fructose-1,6-bisphosphatase, respectively). Acetyl-CoA is an important molecule in metabolism used in many biochemical reactions A citrate can refer either to the Conjugate base of Citric acid, (C3H5O(COO33&minus or to the Esters of citric Due to the reciprocal control of the cycle, acetyl-CoA and citrate also have inhibitory roles in the activity of pyruvate kinase. Reaction The reaction with pyruvate kinase pyruvate kinase PEP ----------> pyruvate / \ ADP ATP

References

  1. ^ Hundal R, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V, Inzucchi S, Schumann W, Petersen K, Landau B, Shulman G (2000). "Mechanism by which metformin reduces glucose production in type 2 diabetes". Diabetes 49 (12): 2063–9. doi:10.2337/diabetes.49.12.2063. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11118008.   Free full textPDF (82 KiB)
  2. ^ Garrett, Reginald H. A kibibyte (a contraction of ki lo bi nary byte) is a unit of Information or Computer storage, established by the International ; Charles M. Grisham (2002). Principles of Biochemistry with a Human Focus. USA: Brooks/Cole, Thomson Learning, 578,585. ISBN 0-03-097369-4.  
  3. ^ Garrett, Reginald H. ; Charles M. Grisham (2002). Principles of Biochemistry with a Human Focus. USA: Brooks/Cole, Thomson Learning, 578. ISBN 0-03-097369-4.  
  4. ^ Garrett, Reginald H. ; Charles M. Grisham (2002). Principles of Biochemistry with a Human Focus. USA: Brooks/Cole, Thomson Learning, 516-517. ISBN 0-03-097369-4.  
  5. ^ Chakravarty, K. , Cassuto, H. , Resef, L. , & Hanson, R. W. (2005) Factors that control the tissue-specific transcription of the gene for phosphoenolpyruvate carboxykinase-C. Critical Reviews of Biochemistry and Molecular Biology, 40(3), 129-154.

External links

Dictionary

gluconeogenesis

-noun

  1. (biochemistry) The metabolic process in which glucose is formed, mostly in the liver, from non-carbohydrate precursors
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