CICLO DE KREBS

CADENA RESPIRATORIA
FOSFORILACION OXIDATIVA
CICLO DE KREBS
 GLYCOGENOLYSIS
glycogen glucose-6-phosphate glucose
GLYCOGEN SYNTHESIS ( 6 carbons)

GLUCONEOGENESIS

GLYCOLYSIS
pyruvate lactate
(3 carbons)
triacylglycerols

CO2
LIPASE
FATTY ACID SYNTHESIS
ketones acetyl CoA fatty acids
KETOGENESIS (2 carbons) FATTY ACID OXIDATION

oxaloacetate citrate

CITRIC ACID CYCLE

CO2

CO2
ESQUEMA MINIMO CICLO DE KREBS
acetyl CoA
(2 carbons)

oxaloacetate citrate

CITRIC ACID CYCLE

CO2

CO2

acetate (2C) condenses with oxaloacetate (4C) → citrate (6C)

2 x decarboxylation reactions → → → reformation of oxaloacetate
4 oxidation reactions and one substrate-level phosphorylation
The citric acid cycle – complete oxidation of acetyl CoA
2C
acetyl CoA
CoASH

NADH 4C 6C
oxaloacetate citrate
NAD+
cis-aconitate

4C 6C
malate isocitrate
NAD+

NADH CO2
H2O

4C 5C
ketoglutarate
fumarate
(oxo-glutarate)

FADH
NAD+
CoASH CoASH

FAD 4C 4C NADH
succinate succinyl CoA
GTP GDP, Pi
CO2
 CH3
C O
SCoA
CICLO DE KREBS acetyl CoA

CoASH

COOH COOH
NADH
citrate synthase CH2 aconitase
C O
malate CH2 HO C COOH
NAD+
dehydrogenase CH2 cis- aconitate
COOH
oxaloacetate COOH
aconitase
citrate

COOH COOH

CHOH CH2

CH2 HC COOH

COOH HC OH
malate COOH
isocitrate

NAD+
isocitrate dehydrogenase
H2O CO2
NADH
fumarase

COOH COOH
CH CH2
CH CH2
COOH C O
fumarate COOH
ketoglutarate
(oxo-glutarate)
COOH COOH
FADH
CH2 CH2 NAD
CoASH CoASH
CH2 CH2
FAD
COOH C O NADH
succinate dehydrogenase succinate SCoA
CO2
GTP GDP, Pi succinyl CoA
ketoglutarate dehydrogenase
succinyl CoA synthetase
Condensation of acetyl CoA and oxaloacetate → citrate
CH3
C O
SCoA
acetyl CoA

CoASH

COOH COOH
citrate synthase CH2
C O
CH2 HO C COOH

COOH CH2
oxaloacetate COOH
citrate
Isomerization → isocitrate

COOH
CH2 aconitase

HO C COOH
CH2 cis- aconitate

COOH
aconitase
citrate

COOH
CH2
HC COOH
HC OH
COOH
isocitrate
Decarboxylation and oxidation → ketoglutarate

COOH
CH2
HC COOH
HC OH
COOH
isocitrate

NAD+
isocitrate dehydrogenase
CO2
NADH

COOH
Oxidation of NADH
CH2
in the electron transport chain
CH2
→ 3 x ATP
C O
COOH
ketoglutarate
(oxo-glutarate)
Decarboxylation and oxidation → succinyl CoA

COOH
CH2
CH2
Oxidation of NADH
in the electron transport chain C O
→ 3 x ATP
COOH
ketoglutarate
(oxo-glutarate)
COOH
CH2 NAD
CoASH
CH2
C O NADH

SCoA
CO2
succinyl CoA
ketoglutarate dehydrogenase
Substrate-level phosphorylation

COOH
COOH
CoASH CH2
CH2
CH2
CH2
C O
COOH
succinate SCoA
GDP, Pi
GTP
succinyl CoA

succinyl CoA synthetase

Dehydrogenation → carbon-carbon double bond
COOH
CH
Oxidation of FADH
CH in the electron transport chain
directly linked to reduction of ubiquinone
COOH → 2 x ATP

fumarate

COOH
FADH
CH2
CH2
FAD
COOH
succinate dehydrogenase succinate
Addition of water across the carbon-carbon double bond

COOH
CHOH
CH2
COOH
malate

H2O

fumarase

COOH
CH
CH
COOH
fumarate
Oxidation to reform oxaloacetate

NADH COOH
C O

NAD+ malate CH2

dehydrogenase
COOH
oxaloacetate

COOH
CHOH Oxidation of NADH
in the electron transport chain
CH2 → 3 x ATP

COOH
malate
 CH3

CICLO DE KREBS C O
SCoA
acetyl CoA

CoASH

COOH COOH
NADH
citrate synthase CH2 aconitase
C O
malate CH2 HO C COOH
NAD+
dehydrogenase CH2 cis- aconitate
COOH
oxaloacetate COOH
aconitase
citrate

COOH COOH

CHOH CH2

CH2 HC COOH

COOH HC OH
malate COOH
isocitrate

NAD+
isocitrate dehydrogenase
H2O CO2
NADH
fumarase

COOH COOH
CH CH2
CH CH2
COOH C O
fumarate COOH
ketoglutarate
(oxo-glutarate)
COOH COOH
FADH
CH2 CH2 NAD
CoASH CoASH
CH2 CH2
FAD
COOH C O NADH
succinate dehydrogenase succinate SCoA
CO2
GTP GDP, Pi succinyl CoA ketoglutarate dehydrogenase
succinyl CoA synthetase
GENERACION DE ENERGIA

Enzimas: superficie interior de la membrana

mitocondrial
Cada NADH genera 3 enlaces de alta energía de ATP
El único FADH2 genera 2 ATP
Un enlace generado GTP
Por cada vuelta del Ciclo de Krebs se producen 12
enlaces de energía de ATP
CADENA RESPIRATORIA
OXIDACIÓN DE LOS MACRONUTRIENTES
Linkage between ATP utilization and oxidation of metabolic fuels

metabolic fuels oxidized

coenzymes H2 O
mitochondrial
electron transport chain
reduced ½ O2
CO2 coenzymes

ATP
(adenosine triphosphate)
ADP (adenosine diphosphate)
+ phosphate

physical and chemical work

PRINCIPIOS DE LAS REACCIONES DE REDUCCIÓN /
OXIDACIÓN (REDOX)
COMPONENTES DE LA CADENA
RESPIRATORIA
Esquemáticamente se conocen cuatro componentes:
I: el FMN (flavin mononucleótico)
II: una proteína que contiene Fe y S (FeS)
la Coenzima Q
III: los citocromos b y c1
el citocromo c
IV: los citocromos a y a3 (citocromo oxidasa)
An overview of the mitochondrial electron transport chain

substrate
oxidation NADH, H+
flavoprotein
CO2 NAD+
ADP + Pi
FADH2 FeS
substrate
flavinH2
ATP
oxidation
ubiquinone
CO2 flavin
ADP + Pi

ATP

cytochrome b
cytochrome c1
cytochrome c

½O2 ADP + Pi
cytochrome oxidase
H2O (cytochromes a and a3)
ATP
PROTEINAS FERROSULFURADAS
COENZIMA Q OXIDADA

COENZIMA Q REDUCIDA
CITOCROMO C
FOSFORILACION OXIDATIVA
NUCLEÓTIDOS DE ADENINA: AMP, ADP Y ATP

NH2
NH2
N N
N
O
N
N N
O CH2 O P OH
N N
OH H
adenosine monophosphate (AMP)
adenine
NH2 OH OH

N
N
O O
N N NH2
O CH2 O P O P OH
OH OH
adenosine diphosphate (ADP) N
N
NH2 OH OH adenosine
N
N N
N
O CH2OH
O O O
N N
O CH2 O P O P O P OH
OH OH OH
adenosine triphosphate (ATP)
OH OH OH OH

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd
 TRIFOSFATOS SIMILARES DE
ADENINA, GUANINA Y URACILO.

NH2 O O
N N
N HN HN

N N H2N N N
H H O N
H
adenine guanine uracil
NH2

N
N
O O O
N N
O CH2 O P O P O P OH
OH OH
OH
adenosine triphosphate (ATP)
OH OH

Presentation copyright © 2002 David A Bender and some images copyright © 2002 Taylor & Francis Ltd
An overview of the mitochondrial electron transport chain

substrate
oxidation NADH, H+
flavoprotein
CO2 NAD+
ADP + Pi
FADH2 FeS
substrate
flavinH2
ATP
oxidation
ubiquinone
CO2 flavin
ADP + Pi

ATP

cytochrome b
cytochrome c1
cytochrome c

½O2 ADP + Pi
cytochrome oxidase
H2O (cytochromes a and a3)
ATP
INHIBIDORES DE LA FOSFORILACIÓN
Nombre
OXIDATIVA
Función Sitio de Acción
Rotenona inhibidor del transporte de e– Complejo I

Amital inhibidor del transporte de e– Complejo I

Antimicina A inhibidor del transporte de e– Complejo III

Cianuro inhibidor del transporte de e– Complejo IV

Monóxido de Carbono inhibidor del transporte de e– Complejo IV

Azida inhibidor del transporte de e– Complejo IV

Transportador
2,4,-dinitrofenol Agente desacoplante
transmembrana de H+

Transportador
Pentaclorofenol Agente desacoplante
transmembrana de H+

Fracción OSCP de la sintasa

Oligomicina Inhibe la sintasa de ATP
de ATP

inhibidor del transporte de e– Complejo II

Malonato
Rendimiento de ATP de la Oxidacion Completa de la Glucosa