cap 3 – energía, catálisis y biosíntesis ja carde, phd universidad adventista alberts et al

Cap 3 – Energía,

Catálisis y Biosíntesis

JA Carde, PhD

Universidad Adventista

Alberts et al.

03_01_A series of enzyme.jpg

Enzimas

03_02_metabolic pathways.jpg

03_03_Catabolic anabolic.jpg

03_04_Biological structur.jpg

Estructuras biológicas: orden

03_05_Toward disorder.jpg

Entropía espontánea diaria

03_06_Second law of thermo.jpg

03_07_forms of energy.jpg

03_12_Oxidation reduction.jpg

Oxidacion: perdida de e-; que se traduce en

Disminucion en los enlaces C-H

03_13_activation energy.jpg

Enzimas: ayudan en la célula a empujar las reacciones por sobre la E de activacion

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!!!

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

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.

03_17_Negative positiveDG.jpg

03_18_Reaction coupling.jpg

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

Entonces una reacciónYX va de

YX ; si tiene ΔG-

o va deYX; si tiene ΔG+

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 laYX, pq habrá mas moléculas haciendo esa

transición PLT el ΔG será mas negativo también

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 [ ] .

*ΔG= AGo + 0.616 ln [X]/[Y]

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

*ΔG= AGo + 0.616 ln [X]/[Y]

-Si las concentraciones de X y Y son 1M; Que pasa con la relación entre ΔG y AGo ?-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

03_19_Chemical equilibrium.jpg

03_20_binding interactions.jpg

Relacion entre K y G

03_25_enzyme’s performance.jpg

03_26_equilibrium point.jpg

03_30_Activated carriers.jpg

03_31_Mechanical model.jpg

03_32_ATP and ADP cycle.jpg

03_33_terminal phosphate.jpg

03_34_ATP hydrolysis.jpg

03_35_NADPH.jpg

03_36_NADPH to cholesterol.jpg

03_37_Acetyl coenzyme A.jpg

03_38_activated carrier.jpg

03_39_Condensation hydrolysis.jpg

03_40_2_Synthesis polymer.jpg

03_40_3_Synthesis polymer.jpg

03_40_Synthesis polymer.jpg

03_42_Synthesis RNA or DNA.jpg

03_27_Reaction rate data.jpg

03_28_A stopped_flow appar.jpg

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.

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.

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.

Inhibicion Competitiva• Effects on Km

• Km is an indication of enzyme-substrate affinity.

• 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. • 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.

03_29_competitive inhibitor.jpg

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.

Inhibicion NO-CompetitivaEffects 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.

Inhibicion DE-CompetitivaProbably 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.

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.

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.

Inhibicion DE-Competitiva

Efecto en Km:Disminuye

Efecto en Vmax:Disminuye

Inhibición

Modelo Michaelis-Menten

Lineweaver Burke