Presentation on theme: "Vías centrales del metabolismo de los carbohidratos"— Presentation transcript:
1 Vías centrales del metabolismo de los carbohidratos
2 El estudio de los carbohidratos debe considerar Central pathways of carbohydrate metabolismConversion of compounds to intermediates usable in central pathwaysMechanisms of energy (ATP) productionSubstrate-level phosphorylationOxidative phosphorylationOther mechanisms of energy transfer
3 El estudio de los carbohidratos debe considerar Metabolic steps involved in the generation and use of reducing activityReduction of pyruvate or other substrates to fermentation end productsBiosynthetic reactions requiring reducing action
4 El estudio de los carbohidratos debe considerar Oxygen involvement in energy-generating reactionsAerobic metabolismAnaerobic metabolismFacultative metabolismMetabolic intermediates serving as biosynthetic precursors
5 El estudio de los carbohidratos debe considerar Reactions that replenish biosynthetic intermediates (anapleurotic reactions)Metabolic and genetic regulatory system
6 Los carbohidratos no son los únicos compuestos utilizados como fuente de energía por los microorganismosFatty acids, lipids, amino acids, purines, pyrimidines, and a wide variety of other compounds can also serve as carbon and energy sources.
7 Los carbohidratos no son los únicos compuestos utilizados como fuente de energía por los microorganismosGenerally, utilization of an alternate substrate involves its conversion to an intermediate intrinsic to one of the central pathways of carbohydrate metabolism.
8 Vias principales del metabolismo de carbohidratos Glucolisis o via de Embden-Meyerhof-Parnas, o via de la Fructosa bisfosfato – aldolasaEntner-Doudoroff o CetogluconatoCiclo oxidativo de la Pentosa fosfatoGluconeogénesis y síntesis de glicógeno.
9 FRUCTOSE BISPHOSPHATE - ALDOLASE OR EMBDEN-MEYERHOF-PARNAS (EMP)PATHWAY OF GLYCOLYSIS.
11 Reacciones más importantes de de la ruta de EMP Phosphorylation of glucose and fructose-6-phosphate by ATPCleavage of fructose-1,6-bisphosphate to trioses by a specific aldolaseStructural rearrangementsOxidation–reduction and Pi (inorganic phosphate) assimilation
14 The enzyme fructose bisphosphate (FPB) aldolase is one of the most critical steps in the pathway. In the absence of this enzyme, glucose or other hexose sugars must be metabolized via one of several alternative pathways,
15 Regulación metabólica de las enzimas de la glucólisis y del ciclo de los ácidos tricarboxílicos
16 Alternate Pathways of Glucose Utilization Warburg and Christiandescribed the oxidation of glucose-6-phosphate to 6phosphogluconate (6-P-G) via G-6-P dehydrogenase). They also described the decarboxylation of 6-P-G to form a pentose sugar.Entner-Doudoroff or Ketogluconate Pathwaydiffers from the EMP pathway primarily in the form of the 6-carbon intermediate that undergoes C3-C3 cleavage (aldol cleavage) to form three-carbon intermediates.
17 Divergent pathways from 6-phosphogluconate Divergent pathways from 6-phosphogluconate. The structural genes for the enzymes in E. coli are indicated by their three-letter designations. In the core pathway, glucose-6-phosphate dehydrogenase (zwf, for zwischenferment) oxidizes glucose-6-phosphate to 6-phosphogluconolactone. The lactone is dehydrated to 6-phosphogluconate via lactonase (pgl). In the pentose pathway, 6-phosphogluconate is oxidized to ribulose-5-phosphate and carbon dioxide by 6-phosphogluconate dehydrogenase (gnd). Phosphoribose isomerase maintains ribulose-5-phosphate and ribose-5-phosphate in equilibrium. In the Entner-Doudoroff pathway, 6-phosphogluconate is dehydrated by 6-phosphogluconate dehydratase (edd) to yield 2-keto-3-deoxy-6-hosphogluconate (KDPG). The enzyme KDPG aldolase (eda) cleaves KDPG to form pyruvate and GA-3-P (glyceraldehyde-3-phosphate). Pyruvate decarboxylase action yields ethanol and carbon dioxide. The GA-3-P is metabolized via the triose phosphate portion of the EMP pathway to yield ethanol and carbon dioxide. The net yield in the Entner-Doudoroff pathway is 2 ethanol + 2 CO2.
22 Oxidative Pentose Phosphate Cycle In this cycle, G-6-P is converted to ribulose-5-phosphate and CO2. Ribulose-5-phosphate is maintained in equilibrium with ribose-5-phosphate (R-5-P) and xylulose-5-phosphate (X-5-P) by the action of ribose phosphate isomerase and ribulose phosphate epimerase. Transketolase converts R-5-P and X-5-P to sedoheptulose-7-phosphate (SH-7-P) and glyceraldehyde- 3-phosphate (GA-3-P). SH-7-P and GA-3-P are converted to F-6-P and erythrose-4- phosphate (E-4-P) via transaldolase. Transketolase also catalyzes the conversion of E-4-P and X-5-P to F-6-P and GA-3-P. By reversal of the FBP aldolase and G-6-P isomerase reactions, GA-3-P and F-6-P may be converted to G-6-P. The G-6-P can then reenter the oxidative pentose cycle.
23 After one turn of the cycle, the net reaction is Encircled P, phosphate group; G-6-P, glucose-6-phosphate; 6-PG, 6-phosphogluconate; F-6-P, fructose-6-phosphate; F-1,6-BP, fructose-1,6-bisphosphate; DOHAP, dihydroxyacetone phosphate; GA-P, glyceraldehyde-3-phosphate.Encircled P, phosphate group; G-6-P, glucose-6-phosphate; 6-PG, 6-phosphogluconate; F-6-P, fructose-6-phosphate; F-1,6-BP, fructose-1,6-bisphosphate; DOHAP, dihydroxyacetone phosphate; GA-P, glyceraldehyde-3-phosphate.
24 Tarea¿Cuál es el destino de los carbonos 3 y 4 marcados con radiactividad de una glucosa que entra a la víaEMBEntner-DoudoroffPentosa fosfatoFosfogluconatoCiclo oxidativo de pentosa fosfato ?
25 Diferencias entre la glucólisis y la via de la pentosa fosfato Glycolysis generates NADH, which can be reoxidized by linkage to the electron transport system, or under anaerobic conditions it can be used to reduce an oxidized substrate, such as pyruvate, to lactate.
26 Diferencias entre la glucólisis y la via de la pentosa fosfato The pentose phosphate pathway generates NADPH, which is used primarily for reducing power in biosynthetic reaction (e.g., the conversion of α- ketoglutarate to glutamate or the incorporation of acetate into fatty acids) and is not linked to the terminal respiratory system.
27 Operation of the TCA cycle under anaerobic conditions.
28 GLUCONEOGENESIS Growth of microorganisms on poor carbon sources, (L-malate, succinate, acetate, or glycerol),requires the ability to synthesize hexoses for the production of other compounds(cell wall mucopeptides, storage glycogen, and other compounds derived from hexose, such as pentoses, for nucleic acid biosynthesis).
29 Pyruvate kinase is not reversible Glycolytic enzymes1. Phosphorylase. Degradation of glycogen or starch to G-1-P.2. Phosphoglucomutase. Isomerization of G-1-P to G-6-P.3. Hexokinase. Phosphorylation of glucose to G-6-P, using ATP Hexokinase also phosphorylatesfructose to F-6-P using ATP (reaction 3a).4. Phosphoglucoisomerase (pgi). Isomerization of G-6-P to F-6-P.5. Phosphofructokinase (pfkA). Phosphorylation of F-6-P to FBP using ATP.6. Fructose bisphosphate (FBP) aldolase (fbaA). Cleaves FBP to GA-3-P and dihydroxyacetonephosphate.7. Triose phosphate isomerase (tpi ). Interconverts GA-3-P and dihydroxyacetone-P.8. Glyceraldehyde-3-phosphate dehydrogenase (gap). Oxidizes GA-3-P to 1,3-diphosphoglycerateusing nicotinamide adenine dinucleotide (NAD+) and inorganic phosphate (Pi)to form NADP + H+.9. Phosphoglycerokinase (pgk). Generates ATP from ADP.10. Phosphoglyceromutase (pgm). Uses 2,3-diphosphoglycerate to convert 3-phosphoglycerateto 2-phosphoglycerate.11. Enolase (eno). Enolization of 2-phosphoglycerate forms high-energy phosphate bond(∼P; encircled P) in phosphoenolpyruvate (PEP).12. Pyruvate kinase (pykA; pykF). Generates ATP from ADP.13. Lactate dehydrogenase. Reduces pyruvate to lactate using NADP + H+.12. Pyruvate kinase (pykA; pykF). Generates ATP from ADP14. Pyruvate carboxylase. Converts pyruvate to oxaloacetic acid (OAA) via carbon dioxide (CO2) fixation using ATP.15. PEP carboxykinase. Forms phosphoenolpyruvate from OAA using GTP..
30 A second irreversible enzyme is phosphofructokinase 5. Phosphofructokinase (pfkA). Phosphorylation of F-6-P to FBP using ATP.16. Fructose-1,6-bisphosphatase. Removes Pi from F-1,6-bisP to form F-6-P.
31 The third bypass reaction required for gluconeogenesis involves dephosphorylation of G-6-P the formation of glucose from pyruvate requires a considerableexpenditure of energy
32 Gluconeogenesis Regulation A major regulatory step is PEP carboxykinase, encoded by pckA in E. coli.By catabolite repression, a process in which gluconeogenesis is inhibited when glucose or other carbohydrate carbon sources are available.
33 Gluconeogenesis Regulation Maximum levels of PEP carboxykinase are induced atthe onset of the stationary phase of growth,to ensure the synthesis of adequate carbohydrate storage reserves orto provide metabolites from the upper part of the EMP pathway as the organism converts proteins to gluconeogenic amino acids.
34 Gluconeogenesis Regulation The stationary phase induction of PEP carboxykinase requiresCyclic AMP anda regulatory signal, (not been fully elucidated)