kreb's cycle (1)
DESCRIPTION
BIOCHEM WK 3TRANSCRIPT
KREB’S CYCLE (TRICARBOXYLIC ACID
(TCA)CYCLE/CITRIC ACID CYCLE)
BIOCHEMISTRY LEC
WEEK 3
METABOLIC PATHWAYS
• A series of consecutive biochemical reactions catalyzed by enzymes that produce a specific end product.
• Catabolism- the breakdown of food stuffs to simple organic chemicals.
• Anabolism- the synthesis of biomolecules from simple organic chemicals.
METABOLIC PATHWAYS
• Very Few metabolites are used to synthesize a large variety of biomolecules:
• Acetyl-Coenzyme A (acetyl-CoA)
• Pyruvate
• Citrate acid cycle intermediates
METABOLIC PATHWAYS
• Three main pathways for energy production:
• Glycolysis
• Citric acid cycle
• Oxidative-Phosphorylation
METABOLIC PATHWAYS
• Certain pathways are involved in both breakdown and buildup of molecules these pathways are called amphibolic. The citric acid cycle is an example of this.
OVERALL GOAL/IMPORTANCE
• Makes ATP
• Makes NADH
• Makes FADH2
• A cyclical series of biochemical reactions that is fundamental to the
metabolism of aerobic organisms, i.e. animals, plants, and many
microorganisms
Geography
• Krebs in mitochondrial matrix• Mitochondrion
– Outer membrane very permeable• Space between membranes called intermembrane space
– Inner membrane (cristae)• Permeable to pyruvate,• Impermeable to fatty acids, NAD, etc
– Matrix is inside inner membrane
The citric acid cycle enzymes are found in the matrix of the mitochondria
OVERVIEW• Described by Hans Adolf Krebs in 1937
• A feature of cell chemistry shared by all types of life.
• A complex series of reactions beginning and ending with the compound oxaloacetate.
• The cycle produces carbon dioxide and the energy-rich compound ATP.
OVERVIEW
• Eight successive reaction steps.
• The six carbon citrate is formed from two carbon acetyl-CoA and four carbon oxaloacetate.
• Oxidation of citrate yields CO2 and regenerates oxaloacetate.
• The energy released is captured in the reduced coenzymes NADH and FADH2.
Conversion of pyruvate to Acetyl CoA
CH3
O
O
O
pyruvate
CO2HSCoA
CH3 SCoA
O
acetyl CoA
NADHNAD+
pyruvate dehydrogenase complex
• 2 per glucose (all of Kreb’s)• Oxidative decarboxylation• Makes NADH
Fates of Acetyl CoA
CH3 SCoA
O
acetyl CoA
Kreb's
CO2, ATP, NADH...energy
ketone bodies
no CHO present
TAG's
• In the presence of CHO– Metabolized to CO2, NADH, FADH2,GTP and, ultimately, ATP
• If energy not being used (Lots of ATP present)– Made into fat
• If energy being used, but no CHO present– Starvation– Forms ketone bodies (see fat metabolism slides)– Danger!
Kreb’s CycleCH3 C
O
SCoAacetyl CoA
C O
CH2C
O
COO
O
oxaloacetate
CoASH
citrate synthase
COO
CH2CCH2
C
OH C O
O
O Ocitrate
aconitase
COO
CHCHCH2C
C O
O
OO
OH
isocitrate
NADNADH
CO2
COO
CCH2CH2
COO
O
isocitrate dehydrogenase
alpha ketoglutarate
NADNADH
CoASHCO2
CCH2
CH2C
OO
OSCoA
succinyl CoA
alpha ketoglutaratedehydrogenase
GDP
GTPCoASH
CC
CC
OO
O O
H
H
succinate
succinyl CoAsynthetase
FAD
FADH2succinatedehydrogenase
CCH2
CH2
COO
OO
fumarate
OH2
CCH
CH2
COO
O O
OH
malatefumarase
NADNADH
malatedehydrogenase
Kreb's Cycle
OH2+
1. Citrate Synthase Reaction
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
+
2. Aconitase Reaction
citrate
aconitase
isocitrate
COO
CH2CCH2
C
OH C O
O
O O
COO
CHCHCH2C
C O
O
OO
OH
• Forms isocitrate
3. 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
4. α-ketoglutarate dehydrogenase
alpha ketoglutarate
NAD NADHCoASH
CO2
succinyl CoA
alpha ketoglutaratedehydrogenase
COO
CCH2CH2
COO
OCCH2
CH2C
OO
OSCoA
• Same as pyruvate dehydrogenase reaction
5. Succinyl CoA synthetase
succinyl CoA
GDP GTP CoASH
succinate
succinyl CoAsynthetase
CCH2
CH2C
OO
OSCoA
CCH2
CH2
COO
OO
• Coupled to synthesis of GTP– GTP very similar to ATP and interconverted later
6. Succinate dehydrogenase
succinate
FAD FADH2
succinyl CoAdehydrogenase
fumarate
CCH2
CH2
COO
OO
CC
CC
OO
O O
H
H
• Dehydrogenation• Uses FAD
7. 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
8. 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 (oxidative phosphorylation)