Supplemental Lecture (97/02/19 update) by Stephen T. Abedon (abedon.1@osu.edu)

1. Chapter title: Glycolysis in Detail
1. A list of vocabulary words is found toward the end of this document
2. Hexokinase
1. Glucose is brought into cells by group translocation or by cotransport.
2. It is then converted to glucose-6-phosphate via the action of the enzyme hexokinase in an irreversible reaction.
3. Note that this intermediate reaction is a glycolysis "priming" step and, in fact, is a consequence of the group translocation of glucose:

     H   H   H   OH  H   H    
     |   |   |   |   |   |    
HO - C - C - C - C - C - C = 0
     |   |   |   |   |        
     H   OH  OH  H   OH       

glucose

|            
| ADP     
|            
V            

     H   H   H   OH  H   H    
     |   |   |   |   |   |    
Pi - C - C - C - C - C - C = 0
     |   |   |   |   |        
     H   OH  OH  H   OH       

glucose-6-phosphate

3. Phosphoglucose isomerase
1. Glucose-6-phosphate is then reversibly converted, via an isomerization reaction, into fructose-6-phosphate:

     H   H   H   OH  H   H    
     |   |   |   |   |   |    
Pi - C - C - C - C - C - C = 0
     |   |   |   |   |        
     H   OH  OH  H   OH       

glucose-6-phosphate

/||                
 ||                
 ||  Phosphoglucose
 ||    Isomerase   
 ||                
 ||/               

     H   H   H   OH      H     
     |   |   |   |       |     
Pi - C - C - C - C - C - C - OH
     |   |   |   |   ||  |     
     H   OH  OH  H   O   H     

fructose-6-phosphate

4. Phosphofructokinase
1. Fructose-6-phosphate is then converted to fructose-1,6-diphosphate in the second "priming" step of glycolysis:

     H   H   H   OH      H     
     |   |   |   |       |     
Pi - C - C - C - C - C - C - OH
     |   |   |   |   ||  |     
     H   OH  OH  H   O   H     

fructose-6-phosphate

|                     
| ADP              
|                     
V                     

     H   H   H   OH      H     
     |   |   |   |       |     
Pi - C - C - C - C - C - C - Pi
     |   |   |   |   ||  |     
     H   OH  OH  H   O   H     

fructose-1,6-diphosphate

5. Aldolase
1. Fructose-1,6-diphosphate is then cleaved by aldolase into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

     H   H   H   OH      H     
     |   |   |   |       |     
Pi - C - C - C - C - C - C - Pi
     |   |   |   |   ||  |     
     H   OH  OH  H   O   H     

fructose-1,6-diphosphate

/||          
 ||          
 ||  Aldolase
 ||          
 ||/         

     H   H                        H   H     
     |   |                        |   |     
Pi - C - C - OH       +      Pi - C - C = O 
     |   |                        |   |     
     H   C = 0                    H   C - 0H
         |                            |     
         H                            H     

glyceraldehyde-3-phosphate & dihydroxyacetone phosphate

6. Triose phosphate isomerase
1. Dihydroxyacetone phosphate is converted into glyceraldehyde-3-phosphate in a reversible reaction which is driven forward by the utilization of glyceraldehyde-3-phosphate in subsequent steps of glycolysis:

     H   H     
     |   |     
Pi - C - C = O 
     |   |     
     H   C - 0H
         |     
         H     

dihydroxyacetone phosphate

/||                  
 ||                  
 ||  Triose Phosphate
 ||     Isomerase    
 ||                  
 ||/                 

     H   H     
     |   |     
Pi - C - C - OH
     |   |     
     H   C = 0 
         |     
         H     

glyceraldehyde-3-phosphate

7. Glyceraldehyde-3-phosphate dehydrogenase
1. Glyceraldehyde-3-phosphate is then further phosphorylated to 1,3-diphosphoglycerate. This phosphorylation is not done at the expense of an ATP, though it is done with the reduction of one NAD⁺.
2. Note that, unlike glyceraldehyde-3-phosphate, 1,3-diphosphoglycerate shares one high energy bond with a phosphate.

     H   H     
     |   |     
Pi - C - C - OH
     |   |     
     H   C = 0 
         |     
         H     

glyceraldehyde-3-phosphate

|                            
|+               
|                            
|  Glyceraldehyde-3-Phosphate
|        Dehydrogenase       
|                            
|-- NADH + H+               
|                            
V                            

     H   H     
     |   |     
Pi - C - C - OH
     |   |     
     H   C ~ Pi
         ||    
         O     

1,3-diphosphoglycerate

8. Phosphoglycerate kinase
1. This is the first substrate-level phosphorylation step of glycolysis. It results in the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate and produces one ATP.

     H   H     
     |   |     
Pi - C - C - OH
     |   |     
     H   C ~ Pi
         ||    
         O     

1,3-diphosphoglycerate

|                         
| ATP                  
|                         
V                         

     H   H     
     |   |     
Pi - C - C - OH
     |   |     
     H   C = 0 
         |     
         OH    

3-phosphoglycerate

9. Phosphoglyceromutase
1. 3-phosphoglycerate is slightly rearranged to form 2-phosphoglycerate:

     H   H     
     |   |     
Pi - C - C - OH
     |   |     
     H   C = 0 
         |     
         OH    

3-phosphoglycerate

/||                      
 ||                      
 ||  Phosphoglyceromutase
 ||                      
 ||/                     

     H   H     
     |   |     
H0 - C - C - Pi
     |   |     
     H   C = 0 
         |     
         OH    

2-phosphoglycerate

10. Enolase
1. A water molecule is then removed from 2-phosphoglycerate to form phosphoenolpyruvate which, you will note, shares one high energy bond with its phosphate.

     H   H     
     |   |     
H0 - C - C - Pi
     |   |     
     H   C = 0 
         |     
         OH    

2-phosphoglycerate2_phosphoglycerate

/||         
 ||         
 ||  Enolase
 ||         
 ||-- H2O  
 ||         
 ||/        

 H - C = C ~ Pi
     |   |     
     H   C = O 
         |     
         OH    

phosphoenolpyruvate

11. Pyruvate kinase
1. This is the second substrate-level phosphorylation step of glycolysis. It results in the conversion of phosphoenolpyruvate to pyruvate, the dephosphorylated compound which signals the end of the glycolysis reactions:

H - C = C ~ Pi
    |   |     
    H   C = O 
        |     
        OH    

phosphoenolpyruvate

|                       
| ATP                
|                       
V                       

    H        
    |        
H - C - C = O
    |   |    
    H   C = O
        |    
        OH   

pyruvate

12. Lactate dehydrogenase
1. The conversion of pyruvate to lactic acid and simultaneous regeneration of NAD⁺ constitutes lactic acid fermentation.

    H        
    |        
H - C - C = O
    |   |    
    H   C = O
        |    
        OH   

pyruvate

|                       
|+          
|                       
|  Lactate Dehydrogenase
| ("running in reverse")
|                       
|-- NAD+               
|                       
V                       

    H   H     
    |   |     
H - C - C - OH
    |   |     
    H   C = O 
        |     
        OH    

lactic acid

13. Vocabulary
1. Aldolase
2. Enolase
3. Glyceraldehyde-3-phosphate dehydrogenase
4. Hexokinase
5. Lactate dehydrogenase
6. Phosphofructokinase
7. Phosphoglucose isomerase
8. Phosphoglycerate kinase
9. Phosphoglyceromutase
10. Pyruvate kinase
11. Triose phosphate isomerase
14. Practice questions
1. No entry.
15. Practice question answers
1. No entry.
16. References
1. No entry.