Cap 3 – Energía, Catálisis y Biosíntesis JA Carde, PhD Universidad Adventista Alberts et al.

Presentación del tema: "Cap 3 – Energía, Catálisis y Biosíntesis JA Carde, PhD Universidad Adventista Alberts et al."— Transcripción de la presentación:

1 Cap 3 – Energía, Catálisis y Biosíntesis JA Carde, PhD Universidad Adventista Alberts et al.

2 03_01_A series of enzyme.jpg Enzimas

3 03_02_metabolic pathways.jpg

4 03_03_Catabolic anabolic.jpg

5 03_04_Biological structur.jpg Estructuras biológicas: orden

6 03_05_Toward disorder.jpg Entropía espontánea diaria

7 03_06_Second law of thermo.jpg

8 03_07_forms of energy.jpg

9 03_12_Oxidation reduction.jpg Oxidacion: perdida de e-; que se traduce en Disminucion en los enlaces C-H

10 03_13_activation energy.jpg Enzimas: ayudan en la célula a empujar las reacciones por sobre la E de activacion

11 03_14_Lowering activation.jpg Mientras mas E por molecula  menos moleculas tienen esa energia!!! La presencia de una Enzima hace que un Numero mayor de moleculas tengan la energia para que la reaccion proceda!!!

12 03_15_Enzymes catalyze.jpg Hay una enzima presente PLT… Selectivas: catalizan una reaccion especifica Rutas especificas: una serie de enzimas presentes determina la ruta metabolica que una molecula X seguira; esto implica: CONTROL

13 03_16_Enzymes convert.jpg Sitio Activo: region en la enzima con caracteristicas unicas para una molecula unica o sea su sutrato. Participan en la reaccion PERO no son alteradas o afectadas.

14 03_17_Negative positiveDG.jpg

15 03_18_Reaction coupling.jpg

16 Reacciones E favorables: crean desorden pq disminuyen la E libre del sistema PLT tienen ΔG negativo Reacciones E desfavorables: crean orden pq aumentan la E libre del sistema PLT tienen AG positivo

17 Entonces una reacción Y  X va de Y  X ; si tiene ΔG- o va de Y  X; si tiene ΔG+

18 Que factores afectan ΔG de una reacción? - la energía almacenada en cada molécula (potencial químico) - las concentraciones de las moléculas en la mezcla Ej: un exceso de Y sobre X favorece la Y  X, pq habrá mas moléculas haciendo esa transición PLT el ΔG será mas negativo también

19 Como yo puedo determinar cuanta diferencia en [ ] se necesita para compensar una disminución en energía química? Con un análisis termodinámico, donde se separa la parte del cambio de energía libre que es dependiente de [ ] de la parte que es independiente de [ ].

20 *ΔG= AG o + 0.616 ln [X]/[Y] - Δg o - depende de las característica intrínsecas de las moléculas (en condiciones ideales) - +… dependiente de las concentraciones - * para una reacción Y  X, 37 o C - ΔG – Kcal/mol - [Y] y [X] – concentraciones de estos - RT = 0.616 constante y ln log natural

21 *ΔG= AG o + 0.616 ln [X]/[Y] -Si las concentraciones de X y Y son 1M; Que pasa con la relación entre ΔG y AG o ? -Si la razón X:Y disminuye, ΔG sera mas negativo, PQ? -Cuando la velocidad de ambas reacciones es igual se llega al equilibrio qumico: estado en el que la razon de X y Y se mantiene constante; K = [X]/[Y]; donde K es la constante de equilibrio; punto donde el efecto de las concentraciones balancea el empuje dado a la reaccion por el ΔG, PLT no hay cambio en energia libre que empuje la reacción hacia ningun lado asi que AG = 0

22 03_19_Chemical equilibrium.jpg

23 03_20_binding interactions.jpg Relacion entre K y  G

24 03_25_enzyme’s performance.jpg

25 03_26_equilibrium point.jpg

26 03_30_Activated carriers.jpg

27 03_31_Mechanical model.jpg

28 03_32_ATP and ADP cycle.jpg

29 03_33_terminal phosphate.jpg

30 03_34_ATP hydrolysis.jpg

31 03_35_NADPH.jpg

32 03_36_NADPH to cholesterol.jpg

33 03_37_Acetyl coenzyme A.jpg

34 03_38_activated carrier.jpg

35 03_39_Condensation hydrolysis.jpg

36 03_40_2_Synthesis polymer.jpg

37 03_40_3_Synthesis polymer.jpg

38 03_40_Synthesis polymer.jpg

39 03_42_Synthesis RNA or DNA.jpg

40 03_27_Reaction rate data.jpg

41 03_28_A stopped_flow appar.jpg

42 Inhibidores Inhibitors are compounds which interact with an enzyme to slow down its rate of reaction Many toxic compounds are enzyme inhibitors, being toxic because they inhibit enzymes responsible for vital reactions. Inhibitors can interact with an enzyme in different ways and enzyme kinetics is a major tool in distinguishing between these mechanisms.

43 Inhibicion Competitiva In the presence of a competitive inhibitor the enzyme can bind to the substrate: to form an enzyme-substrate complex, or the inhibitor: to form an enzyme-inhibitor complex.

44 Inhibicion Competitiva Competitive inhibitors prevent the substrate from binding to the enzyme and thereby prevent the enzyme from converting it to product. They are mutually exclusive with the substrate so prior binding of the substrate prevents the inhibitor from binding. Consequently competitive inhibitors are inactive at very high substrate concentrations and do not therefore alter the maximal velocity. They are active at low substrate concentrations which is seen as an increase in the slope of the Lineweaver-Burk plot. They reduce the affinity of the enzyme for its substrate; seen as an increase in the Michaelis constant.

45 Inhibicion Competitiva Effects on Km Km is an indication of enzyme-substrate affinity.Km In the presence of a competitive inhibitor some enzyme molecules will exist as free enzymes, others as enzyme-inhibitor complexes. So a competitive inhibitor reduces enzyme-substrate affinity, or increases Km. Effects on Vmax Vmax is the velocity at very high substrate concentration.Vmax Under these conditions the inhibitor is competed out by the substrate and does not inhibit the enzyme at all. So competitive inhibitors do not slow the reaction at high substrate concentrations and then is no change in Vmax.

46 03_29_competitive inhibitor.jpg

47 Inhibicion NO-Competitiva A noncompetitive inhibitor binds to an inhibitor site on the enzyme which is remote from the active site and brings about a conformational change in the active site. In this sense it's very similar to one of the competitive inhibitor types. The difference is that this time the change in the active site is such that it does not prevent substrate binding but, rather, prevents the enzyme from converting the bound substrate to product.

48 Inhibicion NO-Competitiva Effects on Km A classical noncompetitive inhibitor has no effect whatsoever on substrate binding so the enzyme-substrate affinity, and hence the Km, are unchanged. Effects on Vmax Noncompetitive, of both the classical and mixed varieties, inhibit at high substrate concentrations so the Vmax is decreased.

49 Inhibicion DE-Competitiva Probably the main claim to fame of uncompetitive inhibitors is the frequent confusion of names between them and noncompetitive inhibitors! The key feature of these inhibitors is they are incapable of binding to free enzyme.

50 Inhibicion DE-Competitiva They can only bind to the enzyme-substrate complex. This could be because the substrate is itself directly involved in binding the inhibitor or because it brings about a conformational change in an inhibitor binding site which was previously incapable of binding the inhibitor. Once the inhibitor has bound it prevents the enzyme from turning the substrate into product. Again this could be some kind of direct interaction, or due to a change in conformation of the active site.

51 Inhibicion DE-Competitiva Uncompetitive inhibitors can bind only to enzyme substrate complex, not to free enzyme. As a result they do not inhibit at very low enzyme concentrations. They show an apparent increase in affinity for the substrate as more substrate binds to the enzyme but only in the formation of an abortive ternary complex.

52 Inhibicion DE-Competitiva Efecto en Km: Disminuye Efecto en Vmax: Disminuye

53 Inhibición

54 Modelo Michaelis-Menten

55 Lineweaver Burke