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Lecture notes of 7 pages for the course Metabolic Pathways at QMUL

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  • March 5, 2021
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  • 2020/2021
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Glycolysis
Learning objectives:

1. Describe in general glycolysis
2. Describe and explain in detail the regulation of glycolysis (i.e. irreversible steps)
3. Identify reactions producing ATP, NADH, FADH 2

Why is glucose so important?

 Only fuel that the brain uses under non-starvation condition
- Under starvation conditions, ketone bodies are used
 Only fuel RBC use at all
 There are many other carbohydrates, so why glucose?
- Can speculate that glucose is formed from formaldehyde under prebiotic (occurring before emergence of
life) conditions so first fuel source for primitive (early stage of evolution) biochemical systems?
- Low tendency (relative to other monosaccharides) to non-enzymatically glycosylate proteins (due to liking in
a ring instead of open chain)




Glycolysis

 Anaerobic (no oxygen) metabolism of glucose (provides energy for short, intense exercise)
 The glycolytic pathway describes the oxidation of glucose to pyruvate with the generation of ATP and NADH
 also called embden-meyerholf pathway
 glycolysis is a universal pathway, which means present in all organisms from yeast to mammals
 in eukaryotes, glycolysis takes place in the cytosol
 in the prescence of O2, pyruvate is further oxidised to CO2
 in the absence of O2 , pyruvate is fermentated to lactate or ethanol

 net reaction:




LO1. DESCRIBE GLYCOLYSIS IN GENERAL

 step 1 : is investment stage
- 2 mols of ATP are consumed for each mol of glucose
- Glucose is converted to fructose-1,6-bisphosphate
- Glucose is trapped inside the cell and at the same time converted to an unstable form that can be readily
cleaved into 3-C units
 Step 2: rearrangement
- Fructose-1,6-bisphosphate is cleaved into two 3-C units of glyceraldehyde-3-phosphate
 Step 3: is the harvesting stage

, - 4 mols of ATP and 2 mols of NADH are gained from each initial mol of glucose
- This ATP is a result of substrate-level phosphorylation
- Glyceraldehyde-3-phosphate is oxidised to pyruvate

LO2. DESCRIBE & EXPLAIN IN DETAIL THE REGULATION OF GLYCOLYSIS (I.E. IRREVERSILBLE STEPS IN GLYCOLYSIS)

LO3. IDENTIFY REACTIONS PRODUCING ATP, NADH, FADH2

Glycolysis- stage 1 trapped & destabilised

 Reaction 1
- Phosphorylation of glucose to glucose-6 phosphate
- Requires energy so coupled to hydrolysis of ATP to ADP + Pi
- Enzymes: hexokinase (via induced fit)
Has a low Km for glucose thus once glucose enters it gets phosphorylated
This step is irreversible
So glucose gets trapped inside cell
glucose transporters transport only free glucose, not phosphorylated glucose




Stage 1 reaction 2

 Isomerisation of glucose-6-phosphate to fructose 6-phosphate
 aldose sugar is converted into the keto isoform
 Enzyme: phosphoglucose isomerase
 Reversible reaction
 fructose-6-phosphate is quickly consumed and forward reaction is favoured.




Stage 1 reaction 3

 Another kinase reaction
 Phosphorylation of the hydroxyl group on C1 forming fructose-1,6-bisphosphate
 Enzyme: phosphofructokinase
 This allosteric enzyme regulates the pace of glycolysis
 Reaction is coupled to the hydrolysis of an ATP to ADP and Pi
 second irreversible reaction

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