L10: Glycolysis Flashcards
Why do we eat?
- Maintain cell integrity and barrier function
- Replenish blood cells
- Replace cells undergoing apoptosis
What are the core energy providing nutrients?
Protein, carbohydrates, fats and lipids
What are the three main phases of cellular respiration?
1) Glycolysis
2) The TCA Cycle (Kreb’s)
3) Electron Transport Chain
What are the monomers for carbohydrates?
Monosaccharides
What are the monomers for fats/lipids?
Fatty acids and glycerol
What are the monomers for proteins?
Amino acids
Where are polymers broken down into their constituent monomers?
- Liver
- Adipose tissue where lipolysis of fatty acids take place
- Muscles - act on amino acids
Where is glycogen stored?
- High concentrations in the liver - releasable into circulation
- High amounts in the muscles - for local use only during exercise/fasting as muscles do not have an enzyme to allow glucose to be exported back into circulation
What is meant by anabolism and catabolism?
- Anabolism is the synthesis of complex polymers from monomers or simple polymers
- Catabolism is the metabolism/break down of complex polymers into monomers or simple polymers
- This is an energy driven process
What happens to lipids in the fed state?
- Lipids enter the gut by absorption
- Lipids pass into the liver and package lipids into triglycerides through very low density lipids (VLDL) proteins and pass into the adipose tissue
- Some to the muscles when required
What happens to glucose in the fed state?
- Glucose enters the gut by absorption
- Glucose is distributed everywhere to include the liver, muscles, adipose
- Most to the brain - main carbon source here
What happens to amino acids in the fed state?
- Amino acids enter the gut by absorption
- To muscle to be used as a fuel source
How can glucose be stored?
Glycogen
What is the structure of glycogen?
- Highly branched glucose polymer with a1,4 and a1,6 linkages
- Stored as granules in the cytosol of cells
What is the benefit of branching in glycogen?
Allows for more glucose to be stored and more free ends available to be metabolised quickly
How is the synthesis and metabolism of glycogen regulated?
Glucagon and insulin will control the synthesis of glycogen and tell the body when to store or when to utilise glycogen
What happens in the fasted state?
- Adipose tissue releases some fatty acids back into circulation to be converted to energy
- Glycogen is broken down by the liver into glucose for the brain to be metabolised
- Glycogen into glucose for muscles if necessary
What happens in the starved state?
- Accelerates the release of free fatty acids from adipose tissue to the liver to convert into energy
- Glucose released in gluconeogenesis - converts acetyl CoA from fatty acids into glucose for the brain
- Ketones provide a source of energy - last resort for energy
What ways can energy be regenerated in starvation?
- Lactate from the muscles in anaerobic metabolism
- Amino acids in transamination from cooperation between muscles and liver to detoxify resultant urea
What is the main source of energy in the human body? How much ATP is produced?
- Glucose is the main energy source
- Produces 28-32 ATP molecules to drive energetic processes
What is the structure of glucose?
What is glycolysis?
- Breaking glucose (6 carbon sugar) into two pyruvate molecules
- Net production of 2 ATP
What cycle does pyruvate enter after glycolysis, to generate more ATP?
TCA/Kreb’s cycle
What other ways can pyruvate be processed?
- Transaminate pyruvate into alanine (for gluconeogenesis) - addition of NH3 group
- Anaerobic respiration (fermentation) to produce lactate from exercise, and yeast can form ethanol
What conditions are required for the metabolism of glucose to produce ATP?
Aerobic conditions
What are the two main phases to glycolysis?
- Investment phase
- Pay-off-phase
What is the investment phase of glycolysis?
- Take glucose and add 2 ATP
- Splits glucose (6 carbon) into two 3 carbon molecules
What is the pay-off phase of glycolysis?
- Convert 3 carbon sugars into pyruvate
- Generating 4 ATPs (net of 2)
What are the 3 different aspects to the 10 different enzymatic reactions in glycolysis?
1) The trap - adding a phosphate whilst using ATP, commiting glucose to the pathway
2) The split - 6 carbon glucose becomes two 3 carbon molecules
3) Pyruvate maker
What mechanism allows cells take up glucose?
- Facilitated diffusion through a family of hexose transporters
- No energy involved
Where is Glut1 transporter found?
- Blood
- Blood-brain barrier
- Heart (lesser extent)
Where is Glut2 transporter found?
- Liver
- Pancreas
- Small intestines
Where is Glut3 transporter found?
- Brain
- Neurons
- Sperm
Where is Glut4 transporter found?
- Skeletal muscle
- Adipose tissue
- Heart
What glucose transporter is the main transporter for the uptake of glucose?
- Glut4
- Made available in the plasma membrane through the action of insulin
What does insulin promote in glucose uptake by Glut4?
Promote a loop for transport of glucose into the muscle, where it can be converted into glucose six phosphate and used in glycolysis, or stored as muscle glycogen
Where is insulin produced?
Pancreas
Summarise the pathway of glycolysis, including the main enzymes
At what point are two of each molecule produced in glycolysis?
- From glyceraldehyde-3-phosphate downwards
- Also produces two of each of the intermediates (4 ATP and 2 NADH)
What are the 3 irreversible steps in glycolysis?
- Glucose-6-phosphate back to glucose
- Fructose-1,6-bisphosphate back to fructose-6-phosphate
- Pyruvate back to phosphoenolpyruvate
What happens if there is an enzyme deficiency/dysfunction at any of the 3 irreversible steps?
Build of metabolites
Why is glucose synthesis from pyruvate important?
- Glucose synthesis needed to supply the brain with enough glucose
- Catabolism and anabolism occur at the same time
- Often spatially separated
How can pyruvate be converted into glucose?
Using bypass reactions to replace the irreversible steps with alternative activities in gluconeogenesis
How is pyruvate converted to phosphoenolpyruvate?
1) Pyruvate to oxaloacetate using enzyme pyruvate carboxylase - uses 1 ATP and CO2
2) Oxaloacetate to phosphoenolpyruvate using enzyme phosphoenolpyruvate carboxykinase - uses 1 GTP and produces CO2
- This produces 1 molecule of each
How is fructose-1,6-bisphosphate converted into fructose-6-phosphate?
1) Bypass 2
2) Uses enzyme fructose-1,6-bisphosphatase
- A phosphate is produced
- No energy involved
How is glucose-6-phosphate converted into glucose?
- Bypass 3
- Uses enzyme glucose-6-phosphatase
- A phosphate is produced
- No energy is involved
What is the energy costs to go from pyruvate to glucose via irreversible reactions?
- 4 ATP
- 2 GTP
- 2 NADH/glucose synthesised
How is glycogen converted to glucose-6-phosphate?
How is fructose inputted into glycolysis?
- Enzyme fructokinase
- Converted into fructose-6-phosphate
- Or fructose in converted to fructose-1-phosphate at inputted into glyceraldehyde-3-phosphate
How is mannose inputted into glycolysis?
Hexokinase to mannose-6-phosphate then fructose-6-phosphate
How are lactose and sucrose inputted into glycolysis?
- Lactose to glucose by lactase
- Glucose to glucose-6-phosphate by hexokinase
- Sucrose to either glucose or fructose using sucrase
- Glucose and fructose inputted to glucose-6-phosphate and fructose-6-phosphate by hexokinase
How is galactose inputted into glycolysis?
- To glucose-1-phosphate by UDP-Galactose
- Enters the same pathway as glycogen
What happens to pyruvate under anaerobic conditions?
- Pyruvate to lactate
- Uses enzyme lactate dehydrogenase
- Reversible reaction
- Often more pyruvate than lactate - driven towards lactate formation
- Regenerates NAD+ from NADH and H+
Why is the regeneration of NAD+ in anaerobic metabolism significant?
- Need NAD+ to generate NADH in glycolysis
- Lots of NADH means a lower concentration of NAD+ - need to regenerate NAD+
What happens to lactate when formed?
- Can enter the Cori cycle in the liver
- Detoxifies lactate into pyruvate which can form glucose
- Short term 2 ATP generated
- Need to input 6 ATP to regenerate (net loss of 4 ATP)
What is lactate acidosis?
- High levels of lactate can build up above 5mM
- Can cause fatigue and stiffness in muscles
What happens to pyruvate in aerobic metabolism?
- Generates NADH + H+ through enzyme pyruvate dehydrogenase
- Coenzyme A is a carrier protein that forms acetyl-CoA and CO2
- NADH can be used to generate energy in the electron transport chain
