kreb's cycle.ppt
TRANSCRIPT
Kreb’s Cycle (Tricarboxylic acidcycle(TCA),
citric acid cycle)
IKRAM ULLAH14
Citric Acid cycleOBJECTIVES
• Brief Overview
• Pyruvate Dehydrogenase Complex (PDC)
• Reactions of TCA cycle or CAC
• Amphibolic nature of TCA cycle
• Regulation of TCA cycle
OVERVIEW
Cyclic process.
Enzymes are located in Mitochondrial Matrix.
Whole process is aerobic.
pyruvate dehydrogenase and TCA cycle reactions take place in mitochondria where oxygen
is utilized to generate ATP by oxydative phosphorylation.
Overall goal
• Makes ATP
• Makes NADH
• Makes FADH2
• Requires some Acetyl CoA to run
In Mitochondria
In Cytosol
Reaction of pyruvate dehydrogenase complex (PDC)
Reaction of TCA cycle: Enzymes Acetyl CoA 2CO 12ATP
Mg
2
REACTIONS OF TCA CYCLECitrate Synthase Reaction (First)
acetyl CoAoxaloacetate
CoASH
citrate synthase
citrate
OH2
CH3 C
O
SCoA
C O
CH2C
O
COO
O
COO
CH2CCH2
C
OH C O
O
O O
+
• Irreversable• A molecule of H O is required• No ATP is required• No Oxidation or decarboxylation.
2
Aconitase Reaction
citrate
aconitase
isocitrate
COO
CH2CCH2
C
OH C O
O
O O
COO
CHCHCH2C
C O
O
OO
OH
• Forms isocitrate• Hydroxyl moved and changed from tertiary to secondary
– (can be oxidized)• 1st dehydretion to form cis Aconitate• The rehydration to form isocitrate
Isocitrate Dehydrogenase
isocitrate
NAD NADH CO2
isocitrate dehydrogenase
alpha ketoglutarate
COO
CHCHCH2C
C O
O
OO
OH
COO
CCH2CH2
COO
O
• All dehydrogenase reactions make NADH or FADH2
• Oxidative decarboxylation
α-ketoglutarate dehydrogenase
alpha ketoglutarate
NAD NADHCoASH
CO2
succinyl CoA
alpha ketoglutaratedehydrogenase
COO
CCH2CH2
COO
OCCH2
CH2C
OO
OSCoA
• Same as pyruvate dehydrogenase reaction• Formation of thioester
Succinyl CoA synthetase
succinyl CoA
GDP GTP CoASH
succinate
succinyl CoAsynthetase
CCH2
CH2C
OO
OSCoA
CCH2
CH2
COO
OO
Succinate dehydrogenase
succinate
FAD FADH2
succinyl CoAdehydrogenase
fumarate
CCH2
CH2
COO
OO
CC
CC
OO
O O
H
H
• Dehydrogenation• Uses FAD
Fumarase
fumarate
OH2
malate
fumarase
CC
CC
OO
O O
H
H
CCH
CH2
COO
O
OH
O
• Addition of water to a double bond
Malate Dehydrogenase
oxaloacetatemalate
NAD NADH
malatedehydrogenase
CCH
CH2
COO
O
OH
O
C O
CH2C
O
COO
O
• Makes NADH• Regenerates oxaloacetate for another round
Net From Kreb’s
• Oxidative process– 3 NADH– FADH2
– GTP
• X 2 per glucose– 6 NADH– 2 FADH2
– 2 GTP
• All ultimately turned into ATP (ETC)
Total Energy per glucose
• Cytosol– Glycolysis
• 2 NADH• 2 ATP
• Mitochondrion– Pyruvate dehydrogenase
• 2 NADH
• Krebs– 6 NADH– 2 FADH2
– 2 GTP
The amphibolic nature of Citric acid cycle:
• Cycle Has dual role.
Catabolic Role
• The Acetyl CoA produced from metabolism of carbohydrates , Proteins and lipids oxidized in this cycle to produce CO , H O and energy as ATP .2 2
Enzymes Acetyl CoA 2CO 12ATP
2
Anabolic Role
• Intermediate of TCA cycle are utilized for Synthesis of Various compounds :
• Synthesis of non essential amino acids
• Haem Synthesis
• Fatty acids and cholestrol synthesis
Regulation of CAC:
• Rate controlling enzymes:
• Citrate synthatase
• Isocitrate dehydrogenase-keoglutaratedehydrogenase
These enzymes are inhibited by ATP , NADH+H ,FADH+H and succinyl CoA.
While activated by ADP , Ca , NAD and FAD.
NOTE: Hormones doesn’t regulate the TCA Cycle
directly.