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Unformatted text preview: Lecture 12
Vitamins and Coenzymes
Overview: • vitamins: essential nutrients required in small amounts • coenzymes: most are modiﬁed forms of vitamins • water-soluble vitamins & coenzymes TPP, pyridoxal phosphate, ﬂavins, coenzyme A, biotin, folate, Vit B12, Fe-containing coenzymes • metal cofactors • lipid-soluble vitamins HW: see handout; 15.1, 15.7, 15.8, 15.9 Roles of vitamins and coenzymes • Metabolic reactions involve chemical changes that could not be brought about by the structures of amino acid side-chain functional groups acting by themselves. In catalyzing reactions, enzymes act in cooperation with smaller organic molecules or metal cations that possess special chemical reactivities or structural properties that are useful for catalyzing reactions. • Vitamins: organic molecules; essential nutrients required in small amounts. • Coenzymes: non-protein molecules that function as essential parts of enzymes. They also serve as carriers that accept or donate chemical groups, H atoms, or electrons. Roles of vitamins and coenzymes • Vitamins: ﬁrst was thiamine (discovered in 1911) • two classes: water soluble or lipid soluble • most coenzymes are modiﬁed forms of vitamins; modiﬁcations take place in the organism after ingestion of vitamins Water soluble: Thiamine (B1); Riboﬂavin (B2); Pyridoxine (B6); Nicotinic Acid (Niacin); Panthothenic Acid; Biotin; Folic Acid; Vitamin B12; Vitamin C Lipid soluble: Vitamin A; Vitamin D; Vitamin E; Vitamin K Others: Inositol; Choline; Carnitine; !-Lipoic Acid; p-Aminobenzoate (PABA); Coenzyme Q Three groups Roles of vitamins and coenzymes 1) High group transfer potential (e.g., ATP, GTP); function in energy coupling within cells 2) Alter structure of a substrate to permit it to react more readily (e.g., coenzyme A, pyridoxal phosphate, thiamin diphosphate, Vit B12) 3) Oxidative coenzymes with speciﬁc oxidation-reduction potentials (NAD+, NADP+, FAD, lipoic acid); carriers of hydrogen atoms or electrons Thiamine pyrophosphate (TPP)
H + N NH2 N S N CH3 O
– CH3 Thiami ne pyr ophosphate
O O C O C O P O – O P O– O OH O C H OH C H The mechanism will be shown in class. Thiamine, or vitamin B1, is converted to TPP, the essential coenzyme involved in the actions of enzymes that catalyze cleavages of bonds shown in red. Bond scission occurs in !-keto acid decarboxylation reactions. Phosphoketolase reactions involve both cleavages shown in the lower box. Transketolase involves the C–C bond cleavage without –OH elimination. Pyridoxal-5’-phosphate
– O NH2 Nicotinamide O NH2 H
N N+ O O O P O O P O H H O NH2 O
– O P O– O OH N+ H CH3 Pyridoxal 5'-phosphate Pyridoxal-5’-phosphate, the coenzyme form of vitamin B6, is involved in reactions with !-amino acids, including transaminations, !decarboxylations, racemizations, !, " eliminations, ",# eliminations, aldolizations, " decarboxylations. The mechanism will be shown in class. Nicoti namide O– OH HO N NH2 N O N N SR OR H C C H C O C O– nicotinamide coenzymes are used in reactions involving hydride transfer; carriers of reducing equivalents, i.e., electrons NH3 +
N R OH OH (or PO3 2 - ) NAD+ or NADP+ NADH or NADPH The mechanism will be shown in class. NAD+ Riboﬂavin and FAD Flavin adenine dinucleotide (FAD) and ﬂavin mononucleotide (FMN) (blue) are the coenzymatically active forms of vitamin B2, riboﬂavin (FMN minus phosphate) isoalloxazine Riboﬂavin and FAD Phosphopantetheine coenzymes Coenzyme A The mechanism will be shown in class. Hydrolysis of thioesters vs. oxygen esters orbital overlap between C and O stabilizes ester Chapter 15: Metabolism: Basic Concepts and Design
fundamental questions: • How does a cell extract energy and reducing power from its environment? 1) How does a cell synthesize the building blocks of its macromolecules and then the macromolecules themselves? These processes are carried out by a highly integrated network of chemical reactions that are collectively known as metabolism or intermediary metabolism. Metabolism overview metabolism: a highly coordinated cellular activity in which multienzyme systems cooperate to 1) obtain chemical energy by capturing solar energy or degrading energy-rich nutrients from the environment 2) convert nutrient molecules into the cell’s own characteristic molecules (including precursors to macromolecules) 3) polymerize monomeric precursors into macromolecules 4) synthesize and degrade biomolecules required for specialized cellular functions two types of living organisms: autotrophs - use CO2 from environment as sole source of carbon heterotrophs - obtain C from complex organic molecules (glucose) metabolism = sum of all chemical transformations in a cell or organism catabolism = degradative phase anabolism = building phase Metabolism overview The number of reactions in metabolism is large; the number of kinds of reactions is small and the mechanisms are usually simple. Metabolic pathways are also regulated in common ways. Glucose metabolism consists of 10 linked reactions. Different products are formed depending on the oxygen levels. Glucosederived carbons of acetyl CoA are subsequently oxidized to CO2. Metabolism overview Metabolism Metabolism is composed of many coupled, interconnecting reactions. Combinations of energy-requiring and energyyielding reactions. Review pp. 411–412 Metabolism Metabolites and metabolic pathways 6C 3C 2C Metabolism overview • chemical reactions in cell are governed by thermodynamics • **thermodynamically unfavorable chemical reactions can be driven forward by coupling with thermodynamically favorable reactions • cells use multistep chemical reactions to extract energy • metabolic pathways are carefully regulated - minimize wasteful processes • cellular energy is generally manifested as phosphorylated organic molecules (ATP) and reduced coenzymes (NADH, FADH2) Thermodynamics !G = change in Gibbs Free Energy !G = !H - T!S -!G favorable (exergonic), spontaneous; +!G unfavorable (endergonic), spontaneous in reverse rxn !H = change in enthalpy (heat absorbed) -!H is favorable (exothermic); +!H is unfavorable (endothermic) T!S = temperature times change in entropy -!S, ordered state; +!S, disordered state (favored) A+B Keq = C+D [C][D] [A][B] A+B Keq = AB [AB] [A][B] linking !G to Keq !G = -RTlnKeq !G = -RTlnKeq Additivity of free energy changes A B sum: A B !G1"° C !G2"° C !G1"° + !G2"° a multi-reaction metabolic pathway can proceed forward with one or more enzyme reactions with +!G"° values if the sum of all the free energy changes of the entire pathway is negative an unfavorable reaction can be coupled with a favorable reaction e.g. phosphorylation of glucose glucose + Pi ATP + H2O glucose + ATP glucose-6-phosphate + H2O ADP + Pi glucose-6-phosphate + ADP !G1"° = +13.8 kJ/mol !G2"° = -30.5 kJ/mol !G"° = -16.7 kJ/mol ATP is the universal currency of free energy Read pp. 412–416 ATP: a large free energy of hydrolysis ATP hydrolysis is exergonic why?? Compounds with high phosphoryl-transfer potential. These have higher phosphoryl-transfer potential than ATP and can be used to phosphorylate ADP to ATP. Hydrolysis of phosphoenolpyruvate (PEP) & 1,3-bisphosphoglycerate Hydrolysis of phosphocreatine (PCr) PCr is a source of phosphoryl group to rapidly generate ATP from ADP; catalyzed by creatine kinase ADP + PCr
Mg2+ ATP + Cr !G!° = -12.5 kJ/mol [PCr] ~30 mM in muscle cells (10 times higher than ATP) creatine is used as a supplement by some athletes Hydrolysis of acetyl-coenzyme A (Ac-CoA) The role of the ATP-ADP cycle is very important to the cell. The fuel molecules in nature are more complex than those on the previous slide, but when they are oxidized, it takes place one carbon at a time. **The carbon-oxidation energy is used in some cases to create a compound with high phosphoryl-transfer potential and in other cases to create an ion gradient. The end point for both is ATP. Compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis. Stages of catabolism: degradation steps (transform fuel into cellular energy) Recurring motifs 1) Activated carriers: NADH, FADH2, NADPH, coenzyme A 2) Key reactions are reiterated oxidation-reduction reactions ligation reactions isomerization reactions group-transfer reactions hydrolytic reactions Energy changes regulate metabolism lyase reactions ...
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