Day 39 Flashcards
Why is CAC amphibolic?
It is responsible for breakdown of pyruvate (catabolic) but its intermediates also play roles in key synthetic pathways (anabolic)
Cataplerotic
reactions that “drain” the CAC’s intermediates
Anaplerotic
reactions that supply the CAC’s intermediates
Cataplerotic Reactions for CAC
- Gluconeogenesis- forming glucose requires oxaloacetate (transported as malate or aspartate to cytosol)
- Fatty Acid and Cholesterol Biosynthesis-requires citrate in the cytosol to be converted to acetyl-CoA
- Porphyrin Biosynthesis-begins with succinyl-CoA in mitochondira
- Amino Acid Biosynthesis- can utilize oxaloacetate and alpha-ketoglutarate
Anaplerotic Reaction for CAC
- Intermediates need to be kept at constant levels to ensure progression of the cycle when needed
- Pyruvate Carboxylase- (from gluconeogenesis) can synthesize oxaloacetate from pyruvate (activated by acetyl CoA because if there is a lot of it that means the cycle is backed up and in need of intermediates)
- Pyruvate can accept an amino group from glutamate to form alanine and alpha-ketoglutarate
The Glyoxylate Cycle
- Only in plants, bacteria, and fungi and it’s enzymes mediate the net conversion of acetyl-CoA to oxaloacetate and takes place in the mitocondria and glyoxysome (specialized peroxisome in plants)
- Very similar except carbon is NOT lost as CO2 and goes directly to oxaloacetate
The Glyoxylate Cycle Steps
1) Glyoxysomal oxaloacetate is condensed with acetyl-CoA to form citrate (citrate synthesis)
2) Citrate is isomerized to isocitrate (aconitase)
3) Isocitrate is cleaved into succinate and glyoxylate (isocitrate lyase)
4) Glyoxylate is condensed with acetyl-CoA to form malate (malate synthase)
5) Malate is oxidized to oxaloacetate (malate dehydrogenase)
6) Succinate produced in glyoxysome can be transported into the mitocondira where is can enter the CAC and get converted into malate
7) Malate can be converted to oxaloacetate in mitochondira, continuing the CAC or…..
8) Malate can be transported into the cytosol where it is converted into oxaloacetate as a precursor to gluconeogenesis
- –*—only in plants
The Glyoxylate Cycle Overview
- Very similar except carbon is NOT lost as CO2 and goes directly to oxaloacetate…..net conversion of two acetyl-CoA to oxaloacteate instead of four CO2’s.
- 2AceCoA + 2NAD+ + FAD — oxaloacetate + 2CoA + 2 NADH + FADH2 + 2H+
In Plants
- only plants have isocitrate lyase and malate synthase
- this allows seeds to convert stored triacylglycerols into glucose and provides 4-carbon units to the CAC to be used with acetyl-CoA derived from fatty acid metabolism
- mammals don’t do this so we can’t convert fats to carbs and we instead fully oxidize acetate to CO2
- human pathogens tuberculosis and c. albicans use this to survive in hosts