Download Citric Acid Cycle - BYU

O
O
C
-
O
C CH3
NAD+
CoA
NADH
CoA
CO2
CoA
O
C CH3
-
O
O
C O
-
C O
NADH
HO C
C O
Step 1
CH2
NAD+
CH2 C O
O
CH2
C O
O
C O
O
-
-
Oxaloacetate (4C)
-
O
C O
Step 2
Citrate (6C)
C CH2 C O
O
HO CH
H
Step 8
-
Isocitrate (6C)
O
C O
HC OH
CH2
C O
O
NAD+
NADH
Step 3
Malate (4C)
C O
O
-
CO2
Citric Acid Cycle
-
-
O
C O
Step 7
α‐Ketoglutarate (5C)
CH2
CH2
-
H2O
Furmate (4C)
O
C O
C O
CH
O
Succinyl CoA (4C)
CH
C O
O
C O
Step 6
-
Succinate (4C)
O
C O
CH2
-
O
C O
Step 5
Pi
O
CoA
NAD+
CH2
C O
C O
FAD
Step 4
CH2
CH2
FADH2
-
CoA
-
CoA
GTP
CO2
NADH
GDP
ADP
ATP
The figure above represents the Citric Acid Cycle (also called the “Krebs Cycle”). The part of the molecule that becomes carbon dioxide is highlighted in a blue box. Notice that a 4 carbon molecule called Oxaloacetate picks up 2 more carbons when it is joined with an acetyl group from Acetyl CoA. Through the beginning steps of the cycle, 2 carbons are lost as carbon dioxide and the
molecule is again restored to a 4 carbon state, ready to pick up another acetyl group. The details of the eight steps above are shown in the following pages. This time, the part of the molecule that undergoes a change is highlighted in blue and the name of the enzyme that catalyzes the reaction is in a green box. Step 1
O
-
-
C O
The CH3 end of the acetyl CoA loses a proton and becomes bonded to the second carbonyl carbon (C=O) of oxyloacetate. The coenzyme (CoA) is subsequently lost with the input of water. +
O
CoA C CH3
-
Citrate Synthase
O
C O
C O
HO C
CH2
Acetyl CoA
H2O
HO C
CH2 C O
O
CH2
CH2 C CoA
O
CH2
C O
O
O
C O
Oxaloacetate
Citrate
S‐Citryl‐CoA intermediate
-
Step 2
O
C O
-
O
C O
H2O
HO C
CH2 C O
O
H CH
An isomerization reaction takes place. This involves the removal of a water molecule and then the insertion of a water molecule. The hydroxyl (OH) group changes position to a different carbon as a result. -
C
H
Aconitase
C O
O
CH2 C O
O
C
-
C CH2 C O
O
HO CH
H
O
C
O
-
O
C O
H2O
C O
O
-
isocitrate
citrate
Cis‐aconitate intermediate
-
Step 3
This is the first of 4 oxidation steps in the cycle. The carbon carrying the hydroxyl group (OH) is converted to a carbonyl group (C=O). CO2 is lost from the intermediate and alpha ketoglutarate is produced. NADH is produced. -
-
O
C O
C CH2 C O
O
HO CH
H
-
H
O
C O
O
Isocitrate
C CH2 C O
O
C
CH2
-
CH2
CO2
C O
O
NADH
NAD+
O
C O
O
C O
Isocitrate
deyhdrogenase
Another oxidation step that results in another loss of CO2. This reaction is very complex and is similar to the reaction that converts pyruvate to acetly CoA. NADH is produced. C O
-
α –Ketoglutarate dehydrogenase
CH2
C O
+ CoA
CO2
C O
O
-
NAD+
CoA is displaced when an inorganic phosphate replaces CoA. Then the phosphate is used to phosphorylate GDP to make GTP. Later the high energy phosphate on GTP can be used to phosphorylate ADP to make ATP. -
O
C O
CH2
CH2
C O
O
O
C O
Succinyl ‐ CoA‐ synthase
CH2
CH2
-
C O
CH2
+ CoA
CH2
C O
CoA
α‐Ketoglutarate
CoA
Succinyl‐CoA
NADH
α‐Ketoglutarate
Step 5
H2O
C O
Pi
-
GDP
Succinyl‐CoA
GTP
O
Succinate
ADP
ATP
Step 6
In this, the third oxidation reaction, two hydrogens are removed from succinate. FAD+ becomes reduced to FADH2. O
-
C O
O
H
H C H
-
C O
Succinate dehydrogenase
H C H
C
C
C O
O
H
C O
-
Succinate
-
-
O
C O
CH2
C O
O
Oxylosuccinate intermediate
Step 4
+ CoA
C O
O
C O
O
-
-
FAD
FADH2
O
-
Furmate
-
Step 7
O
-
O
C O
H
Water is used in this reaction to place a hydroxyl (OH) group on a carbon. C O
Furmase
HO C H
C
C
H C H
H
C O
C O
O
H2O
-
O
O
In this the final of the four oxidation reactions, the carbon carrying the hydroxyl group (OH) is converted to a carbonyl group (C=O). NADH is created as NAD+ accepts the proton and electrons. Oxaloacetate is regenerated and ready to begin step 1 again. -
Malate
Furmate
Step 8
-
O
-
C O
-
C O
Malate dehydrogenase
HO C H
C O
H C H
H C H
C O
C O
O
-
Malate
NAD+
O
NADH
-
Oxaloacetate
Net Results of the Citric Acid Cycle
CoA
O
C CH3
CoA
3‐NAD+
1‐FADH2
3‐NADH
1‐FAD+
2‐CO2
1‐ATP
1‐ADP
The citric acid cycle requires the input of an acetyl CoA. This acetyl CoA generally comes from the break down of glucose (Glycolysis) or from the break down of fatty acids (Beta‐oxidation). One turn of the citric acid cycle releases two carbons as carbon dioxide and produces 3 NADHs, 1 ATP, and 1 FADH2. Ultimately the NADHs and the FADH2 will help with ATP synthesis in the electron transport
chain.