The Krebs Cycle(Citric Acid Cycle)-13 Flashcards
Recap of Carbohydrate metabolism: How does our body regulate glucose levels?
- Control of blood sugar levels by storage in the form of glycogen or by breakdown into glucose
- Metabolic pathways that control either the making or breakdown of glycogen are highly regulated themselves, starting with the hormones insulin and glucagon
Where does Krebs’s cycle take place?
Mitochondrial matrix under aerobic respiration
2 stages of Krebs’s Cycle (starting from glycolysis)
Stage 1: Pyruvate (from glycolysis) is converted to Acetyl-CoA
Stage 2: The acetyl group of acetyl CoA is oxidized via the Krebs cycle (remember from lipid metabolism: B-oxidation of fatty acids produces acetyl-coa which enters the krebs cycle here)
Why is Krebs cycle neither anabolic or catabolic?
Krebs cycle is the hub of aerobic metabolism, being the meeting point of the catabolism of carbohydrates, lipids and amino acids
Intermediates of the krebs cycle are also starting points for many biosynthetic pathways
Therefore, the krebs cycle is amphibolic (both catabolic and anabolic)
Key point of the Stage 1 Acetyl-CoA:
Acetyl-CoA can be produced from different sources, such as amino acids, fatty acids and glucose
Key point of the Stage 2 Acetyl-CoA oxidation:
Energy-carrying (or electron carrying) molecules produced in the Krebs cycle go directly into ETC
How is pyruvate transported into the mitochondrial membrane?
pyruvate (3 carbon molecule) is transported into the mitochondrial matrix via pyruvate translocase located on the inner mitochondrial membrane
Within the mitochondrial matrix, pyruvate is converted to Acetyl CoA (2C) which enters the krebs cycle
A single acetyl-CoA molecule going into 1 turn of the Krebs cycle produces…..
1 ATP molecule
1 FADH2 molecule
2 CO2 molecules
3 NADH molecules
Recall that glycolysis produces 2 pyruvate molecules from each glucose molecule
Therefore the round of mitochondrial matrix reactions (Krebs cycle) occurs TWICE starting from one glucose molecule
What is NADH?
nicotinamide adenine dinucleotide hydride (also known as coenzyme 1)
It is a coenzyme required for many enzymes to function
It is a carrier of 2 electrons and brings them into the electron transport chain
What is the total energy harvest per glucose molecule in the mitochondrial matrix?
Since each glucose yields 2 pyruvate molecules the total energy harvest per glucose molecule in the mitochondrial matrix
2 ATP
8 NADH (2 from the synthesis of acetyl Co-A and 6 from the Krebs cycle)
2 FADH2
6 CO2 (stage 1 you achieve 1 CO2 and then stage 2 you receive 2)
What are the enzymes that control the Krebs cycle?
- Pyruvate dehydrogenase
- Isocitrate dehydrogenase
- a-ketoglutarate dehydrogenase complex
How can we regulate the amount of PDC in the Krebs cycle?
In general, Substrates activate it and products inhibit it
Mammalian PDC are further regulated by covalent modifications of
(1) Pyruvate dehydrogenase kinase
(2) Pyruvate dehydrogenase phosphatase
Kinase will add a phosphate, from ATP to ADP and switch off the enzyme
Phosphatase will remove the phosphate and turn on the enzyme
Regulation of Isocitrate Dehydrogenase, What inhibits and activates Isocitrate Dehydrogenase?
Inhibitor: NADH
Activators: Ca 2+ and ADP
Explain the entire Krebs cycle, including their enzymes:
Stage 1: optional for the conversion of Pyruvate to Acetyl-CoA because Acetyl-CoA may be produced from other sources
(lets assume pyruvate was from the glycolysis pathway)
- Pyruvate is converted to Acetyl-CoA by Pyruvate dehydrogenase (NADH is formed here)
- Acetyl-CoA is converted to Citrate by Citrate Synthase
- Citrate is converted to Isocitrate by Aconitase
- Isocitrate is converted to Alpha-ketoglutarate by Isocitrate dehydrogenase (NADH is formed here)
- Alpha-ketoglutarate is converted to Succinyl-CoA by Alpha-ketoglutarate dehydrogenase (NADH is formed here)
- Succinyl-CoA is converted to Succinate by Succinyl-CoA synthase
- Succinate is converted to Fumarate by Succinate dehydrogenase (FADH2 is formed here)
- Fumarate is converted to Malate by fumarase
- Malate is converted to Oxaloacetate by Malate dehydrogenase (NADH is formed here)
