Committed steps

Question 1

What are the committed steps in Glycolysis? How are they regulated?

Answer 1

1. Hexokinase -
   
   1. glucose —-> glucose 6-phosphate
   2. glucose 6-phosphate inhibits it
2. Phosphofructokinase -
   
   1. fructose 6-phosphate —-> Fructose-1,6-bisphosphate
   2. Inhibits:
      
      1. ATP
      2. Citrate (in liver)
      3. Low pH (in muscle)
   3. Activates:
      
      1. Fructose-2,6-bisphosphate
      2. AMP
3. Pyruvate Kinase
   
   1. Phosphoenolpyruvate ——> Pyruvate
   2. Inhibits:
      
      1. ATP
      2. Alanine
   3. Activates
      
      1. Fructose-1,6-bisphosphate

Question 2

What are the committed steps in Gluconeogenesis? How are they regulated?

Answer 2

1. Pyruvate carboxylase
   
   1. pyruvate —–> Oxaloacetate
   2. Inhibited by:
      
      1. ADP
   3. Activated by
      
      1. Acetyl CoA
2. Phosphoenolpyruvate carboxykinase
   
   1. Oxaloacetate ——> Phosphoenolpyruvate
   2. Inhibited by:
      
      1. ADP
3. Fructose-1,6-bisphosphatase
   
   1. Fructose-1,6-bisphosphate —–> Fructose 6-phosphate
   2. Inhibited by:
      
      1. Fructose-2,6-bisphosphate
      2. AMP
   3. Activated by:
      
      1. ATP
      2. Citrate

Question 3

What are the regulating steps in the citric acid cycle? What regulates them?

Answer 3

1. Pyruvate dehydrogenase complex:
   
   1. Pyruvate —-> Acetyl CoA
   2. Inhibits:
      
      1. NADH, ATP, Acetyl CoA
   3. Activates:
      
      1. ADP
   4. Pyruvate
2. Isocitrate dehydrogenase:
   
   1. Isocitrate —-> Alpha-ketoglutarate
   2. Inhibits:
      
      1. NADH, ATP
   3. Activates:
      
      1. ADP
3. Alpha-ketoglutarate dehydrogenase complex
   
   1. Alpha-ketoglutarate —–> Succinyl CoA
   2. Inhibits:
      
      1. NADH, ATP, Succinyl CoA

Question 4

What are the committed steps in glycogen synthesis and how are they regulated?

Answer 4

1. Glycogen Synthase
   
   1. Adds UDP-glucose residue to glycogen chain.
   2. Inhibited by:
      
      1. changing of A form to B form by glycogen synthase kinase.
   3. Activated by:
      
      1. PP1
      2. Insulin
      3. Changing of B form to A form

Question 5

What are the committed steps in the breakdown of glycogen and how are they regulated?

Answer 5

1. Glycogen phosphorylase
   
   1. Removes a glucose 1-phosphate residue from glycogen
   2. Inhbited by:
      
      1. glucose
      2. ATP
      3. A form changing back to B form.
   3. Activated by:
      
      1. glucose 6-phosphate
      2. Phosphorylation of B form to A form by phosphorylase kinase.
      3. Epinephrine
      4. Glucagon

Question 6

What are the committed steps in fatty acid breakdown and how are they regulated?

Question 7

What are the committed steps in fatty acid synthesis and how are they regulated?

Answer 7

1. Acetyl CoA carboxylase
   
   1. Acetyl CoA —–> Malonyl CoA
   2. Inhibited by:
      
      1. phosphorylation
      2. palmitoyl CoA
      3. Glucagon
      4. Epinephrine
   3. Activated by:
      
      1. dephosphorylation
      2. citrate
      3. Insulin

Question 8

What does HMG-CoA Reductase do and how is it regulated?

Answer 8

1. Catalyzes the comitted step of converting Acetyl CoA and acetoacetyl CoA to Mevalonate in the cholesterol syntheic pathway.
2. Regulation:
   
   1. Control of transcription
      
      1. Sterol regulatory element binding proteins (SREBPs) bind to Sterol regulatory element (SRE) on DNA
      2. Happens when cholesterol levels are low.
   2. Control of translation
      
      1. Non-sterol metabolites derived from Mevalonate inhibit translation of reductase mRNA
   3. Degredation of reductase by ubiquitination
      
      1. membrane domain of reductase senses signals from increasing concentration of sterols
      2. causes it to become polyubiquitinated and ejected from membrane
      3. it is then degraded by proteosome
   4. Phosphorylation in response to ATP levels
      
      1. Phosphorylation of reductase switches it off
      2. phosphorylated by an AMP-activated protein kinase
      3. Thus, cholesterol synthesis stops when ATP level is low.