Diapositiva 1

REGULACION DEL METABOLISMO

DE HIDRATOS DE CARBONO

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Diapositiva 2

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Diapositiva 3

MODULACIÓN ALOSTÉRICA

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Diapositiva 4

MODIFICACIÓN COVALENTE

Proteína quinasa A

Proteína fosfatasa 1

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Diapositiva 5

Factores de transcripción

Promotor
ADN

ARNm

Factores de transcripción

CREB, Sp1, Fos, Jun

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Diapositiva 6

INDUCCIÓN O REPRESIÓN

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Diapositiva 7

Glucosa Glucoquinasa
6-fosfatasa Hexoquinasa

Fructosa Fosfofructoquinasa 1
1,6-difosfatasa (FFQ1)

Fosfoenolpiruvato
carboxiquinasa Piruvato
quinasa

Piruvato
carboxilasa

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Diapositiva 8

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Diapositiva 9

Regulación de la fosforilación de la glucosa:

Glucoquinasa y hexoquinasa

La hexoquinasa tiene mayor afinidad por la

glucosa que la glucoquinasa

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Diapositiva 10

Regulación de la fosforilación de la glucosa:

Glucoquinasa y hexoquinasa

Glucoquinasa Hexoquinasa

Parámetros cinéticos
KM Alto: 10 mM Bajo <100 µM
Vmax Alta Baja

Distribución celular Hígado, células β páncreas Mayoría de los tejidos

Regulación
Rápida Por cambios en la Glucosa 6 P
concentración de glucosa

Mas lenta Inducida por insulina Constitutiva

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Diapositiva 11

Regulación de la glucólisis y de la gluconeogénesis

por la carga energética

Gluconeogénesis

Fructosa 6 P Pi
ATP

ATP Fructosa 1,6

Fosfofructoquinasa 1
FFQ1 AMP bisfosfatasa

CITRATO

ADP Fructosa 1, 6 di P H2O

Glucolisis

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Diapositiva 12

Gluconeogenesis

Fructosa 6 P Pi
ATP

Fructosa 2,6 bisfosfato Fructosa 1,6

Fosfofructoquinasa 1
bisfosfatasa
FFQ1

ADP Fructosa 1, 6 di P H2O

Glucolisis

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Diapositiva 13

Efecto de la Fructosa 2,6 bisfosfato sobre la FFQ1

FOSFOFRUCTOQUINASA 1

FRUCTOSA 6 P FRUCTOSA 1,6 P

Pi
ATP ADP
ATP

H2O
FFQ 2
ADP

FRUCTOSA 2,6 bisfosfato

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Diapositiva 14

Efecto de la Fructosa 2,6 bisfosfato sobre la

Fructosa 1,6 bisfosfatasa

FRUCTOSA 1,6 BISFOSFATASA

FRUCTOSA 1,6 BISFOSFATO FRUCTOSA 6 P

H2O Pi

FRUCTOSA 2,6 BISFOSFATO

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Diapositiva 15

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Diapositiva 16

Regulación hormonal de la glucólisis

y de la gluconeogénesis

Receptores de membrana Receptores intracelulares

Glucagon Cortisol

Insulina

Adrenalina

Acción a través de mensajeros

intracelulares

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Diapositiva 17

Dieta rica
en glúcidos

glucosa

insulina

Dieta rica en glúcidos

glucagon

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Diapositiva 18

GLUCAGON
ADRENALINA
(β-adrenérgico)

Fosfodiesterasa

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Diapositiva 19

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Diapositiva 20

Adenilato
Ciclasa
(forma activa)

Adenina Adenina

AMPc

Adenina

Fosfodiesterasa

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Diapositiva 21

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Diapositiva 22

Transducción de señales hormonales

GLUCAGON
RECEPTOR
γ
β α
AC

R
PDE
R AMP AMPc ATP
C C Activación/
PKA inactiva PKA activa Inducción de
fosfatasas

R R C C

P-OH P-O-P

Transcripción
TRADUCCION Variación del nivel
de expresión de enzimas

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Diapositiva 23

Mecanismo de acción de adrenalina

Adrenalina

Receptor Beta Receptor Alfa

Activacion de Activacion de
Adenilil Ciclasa Fosfolipasa C

AMPc DAG y Ca2+

PKA Activación de PKC

Hígado, músculo Hígado

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Diapositiva 24

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Diapositiva 25

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Diapositiva 26

Mecanismo de acción de insulina

Insulina
Glucosa

ras P-Tyr
Tyr-P
SOS GPI
raf Grb 2 PLC GPI
MEKK SHC

Syp IRS-1 Grb 2 IPG

GLUT 4
MEK p85

PI-3K Proteína
fosfatasa
Mitogénesis
MAPK PKB
Tránsito a través de
C-jun S6 Quinasa II la membrana Síntesis
de
glucógeno

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Diapositiva 27

Regulación de la actividad de la FFQ2 por fosforilación

Alta Baja
Glucemia Glucemia

QUINASA Quinasa
Fosfatasa FOSFATASA

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Diapositiva 28

Regulación de la glucólisis y de la gluconeogénesis

HIPOGLUCEMIA

AMPc PKA FFQ2 INACTIVA F2,6 DI P

(enzima fosforilada,
quinasa inhibida)

GLUCÓLISIS INHIBIDA
GLUCONEOGENESIS ACTIVA

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Diapositiva 29

Regulación de la glucólisis y de la gluconeogénesis

HIPERGLUCEMIA

AMPc PKA FFQ2 ACTIVA F2,6 DI P

(Enzima desfosforilada,
quinasa activa)

GLUCÓLISIS ACTIVA

GLUCONEOGENESIS INHIBIDA

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Diapositiva 30

Regulación de la FFQ2 en hígado y

en músculo cardíaco

Isoforma hepática
Enzima Fosforilada:
Quinasa INACTIVA

Isoforma cardíaca
Enzima Fosforilada:
Quinasa ACTIVA

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Diapositiva 31

Regulación de la piruvato quinasa hepática

PIRUVATO QUINASA-OH
ATP Pi
ACTIVA
Proteína
Proteína fosfatasa
quinasa
ADP
H2O
PIRUVATO QUINASA-OP

INACTIVA

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Diapositiva 32

Glucosa

GLUCONEOGENESIS

Oxaloacetato

Piruvato

Acetil CoA

CICLO DE KREBS

Energia

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Diapositiva 33

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Diapositiva 34

Acción de la insulina sobre la expresión de la glucoquinasa

Insulina

STAT5b STAT5b P

Transcripción
GLUCOQUINASA Traducción

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Diapositiva 35

Glucagon Adrenalina
Adrenalina

GLUCÓGENO GLUCÓGENO

GLUCOSA GLUCOSA

PRECURSORES PRECURSORES

HIGADO MÚSCULO

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Diapositiva 36

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Diapositiva 37

REGULACIÓN DEL METABOLISMO

DEL GLUCÓGENO

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Diapositiva 38

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Diapositiva 39

ADENILATO CICLASA

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Diapositiva 40

Inactiva Activa

Proteína quinasa A

Fosforilasa quinasa Glucógeno sintasa

Activa
Inactiva

Inactiva Activa

Glucógeno
fosforilasa

Glucógeno Glucosa 1-fosfato

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Diapositiva 41

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Diapositiva 42

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Diapositiva 43

REGULACIÓN DE LA ACTIVIDAD DE LA GLUCÓGENO FOSFORILASA

Fosforilasa quinasa b Pi P
ATP Inhibidor 1 a
+
-
Ca2+ Fosfatasa
PKA + de proteínas (PP1)
+
Fosforilasa quinasa a
AMPc ATP
P
Glucosa GLUCÓGENO (n+1)
+ AMP -
Fosforilasa b Fosforilasa a
-
ATP P
+ GLUCÓGENO (n) +
Fosfatasa D-glucosa-1-fosfato
Pi de proteínas (PP1)
P
PKA Inhibidor 1 a -
Fosfatasa
de proteínas
ATP Inhibidor 1 b Pi

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Diapositiva 44

REGULACIÓN DE LA GLUCÓGENO SINTASA

Ca2+

+ +
+
AMPc + +
Ca/CAM quinasa
Fosforilasa Proteína quinasa C
+ quinasa Glucógeno sintasa
quinasa-3
PKA
Caseína
GLUCÓGENO(n) ATP ADP quinasa I y II
UDP-glu
Glucógeno Sintasa b
Glucógeno sintasa a +
P
glucosa 6-P
GLUCÓGENO (n+1)
Pi Fosfatasa de proteínas (PP1)
- P
+ Inhibidor 1 a
AMPc PKA
Pi
ATP Inhibidor 1 b

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Diapositiva 45

glucagon

AMPc

glucógeno
fosforilasa

sintasa

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Diapositiva 46

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Diapositiva 47

Insulina
AMPc (+)

Fosfodiesterasa de
AMPc

UDP-glucosa

5´AM
P fosforilasa
glucógeno
sintasa

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Diapositiva 48

En el músculo…….

adenilato quinasa

ATP + AMP 2 ADP

Keq = [ADP]2
[AMP]. ATP]

[ADP]2
[AMP] =
Keq. [ATP]

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Diapositiva 49

Adrenalina

Impulso nervioso
AMPc
Retículo
sarcoplásmico Ca2+ proteína quinasa A
ATP
contracción ADP Ca2+-calmodulina
muscular Fosforilasa quinasa
AMP P

glucógeno glucógeno
fosforilasa b fosforilasa a

Pi

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Diapositiva 50

Regulación del metabolismo de

glucógeno

En el hígado: insulina/glucagon
[glucosa]sangre
adrenalina

En el músculo esquelético: AMP ATP

Ca2+
adrenalina

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Diapositiva 51

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