BMP: Glycolysis Flashcards
Where is the majority of ATP for the body synthesised and what substance is used?
- Glucose travels to the mitocondria and fuels ATP production
- What fuel source is used by the brain?
- How does the brain obtain this source?
- How much energy is required by the neurones?
- Glucose is the only fuel source used by the brain
- As neurons cannot store glucose, they rely on the blood stream to deliver a constant supply of glucose to the neurons
- Neurones require 2x more energy than oher cells of the body
Where is glucose stored and in what form?
- Liver and muscle store carbohydrate energy in the form of polysaccharide glycogen (long chains of glucose)
Where is the glycogen used from liver and muscle tissue?
- Liver stores glycogen for the whole body
- Muscle has no export mechanism for glucose so sotres glycogen for its own use
What happens when glucose blood levels are too low?
- Liver and muscle’s catabolise stored glycogen into glucose
- Liver releases glucose into the circulation
- muscle uses the glucose directly for energy
What is the most of the bodys energy stored as and why?
Stored as Triglycerides (fat) in speicalied adipocytes.
This is because carbohydrates have a high weight/volume ratio so only 2000 calories of energy of carbohydrates can be stored
Fat has a much lower W/V ratio (lighter)
Fat has a higher energy density (9 cal/g) than carbohydrates (4 cal/g)
When is fat and when is glucose used as energy
- Most tissues use fat as an energy source
- Liver glycogen provides a short term source of carbohydrate
-Carbohydrate stores offer low energy densities, so are most suitable
for short term emergencies
What are normal blood glucose levels?
Why is it important to maintain glucose levels?
- Around 5mM
- Essential for cerebral function
- Above 8 mM - vascular damage
- Below 3mM - Coma and confusion
what organ regulates glucose levels and how?
- Liver
- Helps maintain balance
- Removes glucose when levels too high, replenishes when too low
- Other tissues
- Have no glucose export mechanisms, so glycogen stores are for internal use only
Complete the table
Include names of processes
How is glucose transported?
- Via glucose specific active transporters
- Different isoforms for different tissues
- Glut-1 : BBB, placenta barriers, retinal
- Glut-2: Liver, muscle, pancreatic B cells
- Glut-3: Brain (neurons)
- Glut-4: Cardiac/ skeletal muscle, adipose
- Glut-5: Intestinal epithelium
What are metabolic pathways?
A series of consecutive enzymatic reactions that produce specific products
What are reactant, intermeidates and products referred to in metabolic pathways?
Metabolites
What 2 types of metabolic pathways/ types of metabolism are there?
- Catabolism (catabolic reactions)
- Anabolism (anabolic reactions)
What is catabolic reactions?
What type of reactions are these known as?
The degradation/oxidation of complex metabolites into simpler products
Exergonic reactions: Reactions which release energy. In this case by the synthesis of ATP from ADP or reduction of coenzymes e.g. NAPD to NAPDH
Give an example of catabolic reactions
- Lots of substances are catabolically broken down to produce ATP. ATP is used for almost every energy-requring reaction
- The cleavage of a phosphate group from ATP results in the coupling of energy to metabolic reactinos and a by product of ADP
What are major catabolic oxidation pathways of glucose?
Glycolysis, electron transport chain, Tricarboxylic acid cycle
Give the equation for the anabolic and catabolic reaction of ATP synthesis
- What is anabolic reactions and examples?
- What do these type of reactions need?
- Create new complex biomolecules that are not normally sufficent in food e.g. proteins and nucleic acids
- Building blocks, ATP, reducing power which comes from NADH or NADPH
- The oxidesed form (NAD+ and NADPH+) are used in anabolic reactinos e.g. lipid or nucleic acid synethesis
Describe the catabolic principles
- •Stage I – Oxidative metabolism of a large number of diverse substances (lipid/carbohydrate/protein) to precursor components
- •Stage II – Resultant biomolecules degraded to small number of common intermediates (pyruvate, acetyl co A)
- •Stage III – stage I & II products completely oxidised to CO2, resulting electrons transferred to NAD+ and intermediates for biosynthesis are generated
- •Stage IV – electron transport chain and oxidative phosphorylation yielding H2O and ATP
Complete the diagram
X, Y, Z
A, B, C, D, E, F
1, 2, 3
Over view of glycolysis:
- Where does it occur?
- How many steps are involved?
- What is produced and how?
- From the above question. What happens to the produced product?
- How is energy produced?
- Cytosol of the cell of prokaryotes or Eukaryotes
- 10 enzyme catalysed reaction steps
- A 6 carbon sugar (glucose) is catabolically oxidised to 3 carbon pyruvate.
- Pyruvate is an intermediate and can be converted to acetyl coenzyme A (CoA) to feeding into the TCA cycle)
- Directly via ATP and indirectly through reduction of NAD+ to NADH
What is the net reaction for glycolysis?
What is the first stage in glycolysis?
- Glucose is phosphorylated to Glucose-6-phosphate (G-6-P) by a hexokinase, specifically glucokinase.
- This utilises 1 ATP (i.e ATP to ADP)
- As there is a high negative free energy this reaction is irreversible and glucose is committed to metabolism
- G-6-P is trapped in the cell and can’t cross the membrane
What is step 2?
Glucose-6-P is converted to Fructose-6-P by phosphoglucose isomerase
What is the 3rd step?
- Phosphofructokinase in the rate limiting enzyme in glycolysis
- It catalyses the phosphorylation of F-6-P to Fructose-1,6-bisphosphate (F-1,6-bis P).
- The step utilises 1 ATP
- This step is considered the commited step of glycolysis and is thermodynamically irreversbile
Describe what happens during stage 4
There is cleavage of F-1,6-bis P by aldolase to 3 carbon products: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate
What happens in stage 5?
Triose phosphate isomerase converts a second molecule of DHAP to glyceraldehyde-3-phosphate
Only G-3-P can be used in glycolysis
Aldose or ketose?
G-3-P and DHAP?
- G-3-P aldose
- DHAP - Ketose
What is step 6?
- Catalyses 1st step of phase II
- Dehydrogenation and concomitant phosphorylation of G-3-P to 1,3 bis phosphoglyerate (1,3 BPG) by glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
- Yields NADH (NAD+ reduced to NADH)
- 1,3 BPG contains a high energy thioester bond
What is stage 7?
- Transfer of one phosphate group from 1,3 bis phosphoglycerate to ADP by Phosphoglycerate kinase yielding 1 ATP and 3-phosphoglycerate
- Hydrolysis of thioester bond drives this reaction
What happens in step 8?
- Phosphoglyceromutase catalyses isomerization of 3-phosphoglycerate to 2-phosphoglycaerate
What happens in stage 9?
Enolase catalyse the dehydration of 2-phosphoglycerate to phosphoenolpyruvate
What happens in step 10?
- Last step of glycolysis
- Pyruvate kinase transfers a phosphate group from phosphoenolpyruvate to ADP to produce pyruvate and a second molecule of ATP
- Hydrolysis of high energy PEP bond yields approx. 14 kcal/mol of energy
- free energy of PEP hydrolysis drives ATP synthesis
What is the difference between steps 1 and 2`
- Phase 1: steps 1-5 and energy consuming
- Phase 2: Steps 6-10 and energy generating
- Phase 2 happens 2 per glucose molecule
Discuss glycolysis and genetic disease
- •Genetic
- Rare due to the importance of this metabolic pathway
- Mutations resulting in inability of the cell to respire = death at early stage
- Rare due to the importance of this metabolic pathway
- Pyruvate kinase deficiency
- Chronic haemolytic anaemia
- •GAPDH
- Neurodegenerative disease?
Discuss cancer and glycolysis
- –GAPDH overexpressed in multiple human cancers
- –Malignant rapidly growing tumour cells have high glycolytic rates
- •~ 200 times faster
- –The “Warburg effect ”
- •increased glycolysis is a normal protective process of the body ?
- – Can be utilized to aid detection
- • imaging of malignancies with high aerobic glycolytic rates
- •Uptake of radiolabelled hexokinase substrate
- – 2-(18F)-2 deoxyglucose (FDG) in PET scanning
