TCA Cycle Flashcards
What molecules does 1 pyruvate molecule form during the TCA Cycle?
- 3 NADH
- 1 FADH2
- 1 ATP
- 2CO2
When is the TCA cycle activated and inhibited?
ACTIVATED - high energy demands and low ATP
INHIBITED - low energy demands and high NADH
How does pyruvate form Acetyl CoA?
- Pyruvate transported from cytosol to mitochondrial matrix
- Oxidised and decarboxylated by PDH
- Acetyl group transferred to CoA - form Acetyl CoA. CO2 produced, NAD+ reduced to NADH
- Acetyl CoA enters TCA cycle
Outline the main features of the TCA cycle.
- 4 oxidation steps where FAD and NAD+ are reduced
- 2CO2 given off
- 1 ATP molecule synthesised per molecule of pyruvate
Describe Step 1
- Oxaloacetate (4C) and Acetyl CoA (2C) join to form citrate
- Catalysed by citrate synthase
Describe Step 2
- Isomerisation of citrate to isocitrate
- Reversible
- Catalysed by aconitase
Describe Step 3
- Isocitrate oxidised to oxalosuccinate, forming NADH
- Undergoes decarboxylation to α-ketoglutarate
- Irreversible - catalysed by isocitrate dehydrogenase
- RATE LIMITING STEP - IDH allosterically regulated (Activated by ADP, Inhibited by ATP and NADH)
Describe Step 4
- α-ketoglutarate decarboxylated and binds to CoA to form succinyl CoA
- NAD+ reduced to NADH
- Irreversible - catalysed by α-ketoglutarate dehydrogenase
Describe Step 5
- Cleavage of Succinyl CoA to Succinate
- Energy from hydrolysis used for phosphorylation of GDP to GTP
- Transfer of phosphate group from GTP to ADP
- ATP forms
Describe Step 6
- Dehydration of succinate to fumarate
- Removal of hydrogen from 2 carbon atoms
- Double bond forms
- Reduction of FAD to FADH2
Describe Step 7
- Hydration of fumarate to malate
Describe Step 8
- OH group in malate oxidised to oxaloacetate
- NAD+ reduced to NADH
- Oxaloacetate regenerated and enters next cycle
Describe gluconeogenesis.
- Synthesis of glucose from non-carbohydrate precursors
- Occurs when glycogen stores are depleted
- Takes place in liver and cortex of kidneys
- First substrate is pyruvate (REVERSE OF GLYCOLYSIS)
What does it mean for a substrate to be glucogenic?
- Can be converted to pyruvate or intermediates for TCA cycle
Give examples of glucogenic substrates
- LACTATE - Anaerobic glycolysis via Cori cycle
- GLYCEROL - Triglyceride hydrolysis in adipose tissue
- GLUCOGENIC AMINO ACIDS - Mainly alanine and glutamine (except ketogenic leucine and lysine - convert to fatty acids)
Describe the Cori Cycle
- Lactate produced during anaerobic conditions in muscle
- Lactate accumulates and moves to liver via bloodstream
- Oxidised to pyruvate by LDH - converted to glucose which is carried back to muscles.
What occurs to glycerol during gluconeogenesis?
- Phosphorylated and oxidised to dihydroxyacetone phosphate (glycolysis intermediate)
What occurs to glucogenic amino acids?
- Undergoes transamination
- Generates either pyruvate or oxaloacetate
Compare and contrast glycolysis and gluconeogenesis
- GLUCONEOGENESIS - different enzymes for rate-limiting steps
- Steps occur in reverse to glycolysis. Pyruvate converted to phosphoenol pyruvate then bisphosphate then glucose
What stimulates and inhibits gluconeogenesis?
- Glucagon stimulates/insulin inhibits gluconeogenesis
- Low ATP indicate low energy - inhibit F16BP - decrease gluconeogenesis (increase glycolysis)
- High ATP and citrate indicate high energy - activate PEPCK and F16BP - increase gluconeogenesis (decrease glycolysis)
How is gluconeogenesis involved in Type 2 diabetes?
- Disease due to insulin resistance
- Insulin unable to increase with blood sugar
- Cannot inhibit PEPCK, leading to increased gluconeogenesis and hyperglycemia
What is the mechanism of action of metformin?
Inhibits gluconeogenesis
What are the rate-limiting enzymes in glycolysis and gluconeogenesis?
- GLYCOLYSIS - Phosphofructokinase
- GLUCONEOGENESIS - Fructose 1,6 - bisphosphatase
