Glycolysis Flashcards
Why is there so many steps in glycolysis?
- chemistry easier in small steps
- efficient energy conversion
- versatility
- allows control
Which enzyme catalyses the conversion of glucose to glucose-6-phosphate?
- Hexokinase in most cells
- Glucokinase in LIVER, brain, gut, pancreas (no product inhibition)
Note: glucose-6-phosphate is negatively charged so can’t cross back out of membrane
How is the production of G-6-P regulated?
-Product inhibition
Which enzyme catalyses the conversion of Fructose-6-Phosphate to Fructose-1-6-bisphosphate? How is this enzyme regulated?
-Phosphofructokinase
- inhibited by high ATP:AMP ratio in muscle
- stimulated by high insulin:glucagon ratio in liver
- conversion requires ATP
- ADP is byproduct
When and how is Dihydroxyacetone Phosphate produced?
- side product of conversion of Fructose-1-6-Bisphosphate to Glyceraldehye-3-phosphate
- DHAP can be used for triglyceride production (glycerol backbone) or it can move back into glycolysis (converted into Glyceraldehyde-3-Phosphate)
- Enzyme Glycerol-3-Phosphate Dehydrogenase used in conversion to or from triglyceride (NAD+/NADH are cofactors)
How is phosphoenolpyruvate converted into pyruvate? (enzyme)
- removal of Pi
- ADP converted into ATP
- Pyruvate Kinase stimulated by high insulin:glucagon ratio
How does NADH concentration affect rate of glycolysis?
- NADH is high energy signal
- High concentration of NADH causes product inhibition of step 6 (conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate)
Summarise the key points of glycolysis
Occurs in all tissues (cytosolic)
Functions:
- Oxidise glucose
- Synthesis of 4 mol ATP from 2 molADP
- Produces C6 and C3 intermediates
Features:
-Oxidative
-Exergonic
-C6 becomes two C3
-With one additional enzyme glycolysis is the only pathway that can operate anaerobically
Irreversible
Describe fructose metabolism and its relation to glycolysis
Sucrose = Fructose + Glucose
Metabolism occurs in the liver (soluble enzymes)
1) Fructose converted to Fructose-1-P (ATP converted to ADP, Fructokinase)
2) Fructose-1-P converted to 2-Glyceraldehyde-3-Phosphate, which enters glycolysis (Aldolase)
Describe the production of lactate
- produced from glucose and alanine via pyruvate
- 40-50g synthesis per 24 hours
- increase with strenuous exercise
- Pyruvate reduced to Lactate by enzyme Lactate Dehydrogenase
- NADH required
Describe how galactose is metabolised and how it links to glycolysis
-Metabolism in liver (soluble enzymes)
3 steps:
1) Galactose is converted into Galactose-1-P (ATP converted to ADP, Galactokinase enzyme used)
2) Galactose-1-P is converted into Glucose-1-P (Galactose-1-P uridyl transferase enzyme used)
3) Glucose-1-Phosphate converted into Glucose-6-Phosphate via phospoglucomutase
Describe the clinical condition of Galactosaemia
- Absence of enzymes metabolising galactose, 2 kinds:
- Galactokinase deficiency causing galactose to accumulate (rare)
- Transferase deficiency causing galactose and galactose-1-Phosphate in liver (common)
How does galactosaemia link to cataracts?
in eye:
- Galactose –> Galactitol (via Aldose Reductase)
- NADPH converted to NADP+ in process.
- NADPH in lens of eye is depleted and causes cataracts to form. This is because NADPH is involved in maintenance of free sulphydryl groups on proteins. When it is depleted, inappropriate bonds form. Loss of structural and functional integrity of some proteins that depend on free -SH groups.
Describe how enzymes in glycolysis are allosterically regulated
Step 1- High levels of G-6-P inhibit hexokinase, signalling that the cell no longer needs glucose for energy.
Step 3- In muscle cells, phosphofructokinase is inhibited by high ATP:AMP ratio. In liver it is stimulated by high insulin:glucagon ratio.
Step 10- Pyruvate Kinase is stimulated by high insulin:glucagon ratio. This is dephosphorylation
What is the difference between fructosuria and fructose intolerance?
Fructosuria: fructokinase enzyme missing and fructose released in urine
Fructose intolerance: aldolase missing, fructose-1-P accumulates in liver causing liver damage
Describe the clinical relevance of elevations in plasma lactate
- Blood concentrations normally constant
- lactic acidosis can arise when plasma lactate persistently elevated
What are the products of glycolysis?
- 4ATP (2 ATP initially invested)
- 2NADH (converted from NAD+)
How does cancer affect glycolysis?
Rate of glycolysis up to 200x greater in cancer
How is NAD+ regenerated?
Lactate dehydrogenase
ADH + H+ + pyruvate is converted to NAD+ + lactate in a reversible reaction via Lactate dehydrogenase.
In low oxygen conditions, pyruvate turns into lactate rather than going onto krebs cycle and oxidative phosphorylation.
How is lactic acidosis defined?
- above 5 mM
- above renal threshold
- blood pH lowered
critical marker
What is the pentose phosphate pathway?
Starts from Glucose-6-phosphate
• Important source of NADPH required for: • Reducing power for biosynthesis • Maintenance of GSH levels • Detoxification reactions
• Produces C5-sugar ribose required
for synthesis of :
- Nucleotides,
- DNA & RNA.
- No ATP synthesised. CO2 produced
• Rate limiting enzyme is:
Glucose 6-phosphate dehydrogenase
How is pyruvate dehydrogenase regulated?
High energy signals- ATP etc inhibit
Low energy signals- ADP, insulin etc stimulatory
Describe the clinical condition of Glucose-6-Phosphate Dehydrogenase Deficiency
- point mutation in X-linked gene coding for the enzyme
- common inherited defect
- In red blood cells, inappropriate disulphide bonds form (lack of NADPH) and as a result proteins become aggregated and insoluble heinz bodies form, ultimately resulting in haemolysis
