The link reaction and the Krebs cycle · Biology Class… | StemPy Lab
Course 10.2·Lesson 1 of 3
The link reaction and the Krebs cycle
With oxygen, pyruvic acid goes into the matrix of the mitochondrion. The link reaction turns it into acetyl CoA, with 1 carbon dioxide and 1 NADH. Acetyl CoA joins oxaloacetic acid in the Krebs cycle, which releases 2 carbon dioxide and forms 3 NADH, 1 FADH2 and 1 ATP in each turn.
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Into the mitochondrion
Glycolysis gives only 2 net ATP, and it leaves most of the energy of the glucose in the pyruvic acid. With oxygen, the cell takes the pyruvic acid into the mitochondrion, where most of the ATP is made, and breaks it down completely.
A drawing of a mitochondrion as an oval. The outer membrane is orange, and inside it a purple inner membrane makes a second oval, with a narrow intermembrane space between the two. Four folds of the inner membrane, the cristae, point into the middle. Small green knobs along the cristae are the F0F1 particles of ATP synthase. The space inside the inner membrane is the matrix. A caption says that the link reaction and the Krebs cycle take place in the matrix, and the electron transport system and ATP synthase are in the inner membrane.
A mitochondrion has two membranes. The outer membrane is smooth. The inner membrane is folded into cristae. Inside the inner membrane is the matrix.
The two main events of aerobic respiration are these.
The complete oxidation of pyruvic acid, by the removal of all its hydrogen atoms, leaving three molecules of carbon dioxide. This takes place in the matrix.
The passing of the electrons of these hydrogen atoms to oxygen, with the making of ATP. This takes place on the inner membrane, and the next lesson tells how.
The link reaction
Pyruvic acid enters the matrix. There it is changed to acetyl CoA by oxidative decarboxylation. The enzyme is pyruvic dehydrogenase. The reaction also needs NAD+, coenzyme A (CoA) and magnesium ions.
pyruvic acid+CoA+NAD+⟶acetyl CoA+CO2+NADH+H+
Pyruvic acid has 3 carbon atoms. Acetyl CoA carries an acetyl group with 2 carbon atoms. One carbon is lost as carbon dioxide.
One NADH is formed.
One glucose gives 2 pyruvic acid, so this step gives 2 carbon dioxide and 2 NADH for each glucose.
This step joins glycolysis to the Krebs cycle, which is why it is called the link reaction.
The Krebs cycle
The cycle is also called the tricarboxylic acid cycle (TCA cycle), after its citric acid, which has three carboxyl groups. Hans Krebs worked out the steps. It is a cycle because it ends with the compound with which it starts.
The Krebs cycle drawn as a ring of ten compounds, clockwise from the top left: oxaloacetic acid with four carbons, citric acid with six, cis-aconitic acid, isocitric acid, oxalosuccinic acid, alpha-ketoglutaric acid with five, succinyl CoA with four, succinic acid, fumaric acid and malic acid, which leads back to oxaloacetic acid. Labels beside the arrows: acetyl CoA with two carbons joins and CoA is released between oxaloacetic and citric acid; NAD plus becomes NADH between isocitric and oxalosuccinic acid; carbon dioxide is released after oxalosuccinic acid; NAD plus becomes NADH and carbon dioxide is released between alpha-ketoglutaric acid and succinyl CoA; GDP becomes GTP between succinyl CoA and succinic acid; FAD becomes FADH2 between succinic and fumaric acid; water is added between fumaric and malic acid; NAD plus becomes NADH between malic acid and oxaloacetic acid.
Start. Acetyl CoA (2 carbon atoms) joins oxaloacetic acid (OAA, 4 carbon atoms) and water. The product is citric acid (6 carbon atoms). The enzyme is citrate synthase, and CoA is released.
Middle. Citric acid changes to isocitric acid. Then two decarboxylations follow, one after the other.
Isocitric acid, through oxalosuccinic acid, loses a carbon dioxide and becomes α-ketoglutaric acid (5 carbon atoms).
α-Ketoglutaric acid loses a carbon dioxide and becomes succinyl CoA (4 carbon atoms).
End. Succinyl CoA is changed to succinic acid. Then comes fumaric acid, malic acid and, at last, OAA. The cycle can turn again.
Along the way the carriers are filled.
NAD+ becomes NADH + H+ at three places: isocitric acid, α-ketoglutaric acid and malic acid.
FAD becomes FADH2 at one place: succinic acid to fumaric acid.
GTP is made when succinyl CoA becomes succinic acid. GTP passes its phosphate to ADP and gives ATP. This is substrate level phosphorylation.
One turn of the cycle
Product
Carbon dioxide
2
NADH
3
FADH2
1
ATP (from GTP)
1
The total for one glucose
One glucose gives 2 pyruvic acid, so there are 2 link reactions and 2 turns of the cycle.
Link reaction
Krebs cycle (2 turns)
Together
Carbon dioxide
2
4
6
NADH
2
6
8
FADH2
0
2
2
ATP
0
2
2
All six carbon atoms of the glucose have left as carbon dioxide. Only 2 ATP have been made directly, but 8 NADH and 2 FADH2 carry a large part of the energy to the next stage.
The cycle needs the OAA to be made again, and it needs NAD+ and FAD back from the NADH and FADH2. The electron transport system does that, and only when oxygen is present.
You should find that each pyruvic acid gives 3 carbon dioxide, 4 NADH, 1 FADH2 and 1 ATP, so a glucose, with 2 pyruvic acid, gives 6, 8, 2 and 2.
Try it in Python
The program adds up the link reaction and the Krebs cycle for the two pyruvic acid of one glucose.
Practise with new numbers
Common mistakes
Putting the Krebs cycle in the inner membrane. It is in the matrix.
Forgetting the link reaction. It lies between glycolysis and the cycle, and it gives 1 carbon dioxide and 1 NADH for each pyruvic acid.
Counting one turn for each glucose. One glucose gives 2 pyruvic acid, so there are 2 turns.
Saying that the cycle makes lots of ATP. It makes 1 ATP in each turn. Most of the energy is in the NADH and FADH2.
Saying that the cycle uses oxygen. No step uses oxygen. It is needed later, to make NAD+ and FAD again.
Remember these
Link reaction: pyruvic acid, CoA and NAD+ give acetyl CoA, carbon dioxide and NADH. Enzyme: pyruvic dehydrogenase. Matrix.
Krebs cycle: acetyl CoA (2C) and OAA (4C) give citric acid (6C). Citrate synthase.
Two decarboxylations: α-ketoglutaric acid (5C) and succinyl CoA (4C).
One turn: 2 carbon dioxide, 3 NADH, 1 FADH2, 1 ATP from GTP.
One glucose: link reaction and cycle together, 6 carbon dioxide, 8 NADH, 2 FADH2, 2 ATP.
Check yourself
Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.
Where in the mitochondrion does the Krebs cycle take place?
What are the products of the link reaction for one pyruvic acid?
Name the first product of the Krebs cycle, and the two compounds that make it.
At how many places in one turn is NADH formed, and where is FADH2 formed?
How many carbon dioxide molecules does one glucose give in the link reaction and the Krebs cycle together?
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