Gluconeogenesis Flashcards
Which THREE enzymes (and steps) of glycolysis are bypassed in gluconeogenesis?
And why?
- Step 1: hexokinase
- Step 3:
phosphofructokinase - Step 10: pyruvate kinase
These three steps are the key driving force reactions of glycolysis, and cannot be easily reversed like some of the others.
Define:
Gluconeogenesis
The anabolic pathway that synthesises glucose from certain non-carbohydrate but carbon-based metabolites.
Where does gluconeogenesis mostly occur?
- Liver (~90%)
- Kidneys (~10%)
List:
FOUR key substrate categories of gluconeogenesis in animals.
- Lactate
- Amino acids (barring Lys & Leu)
- Glycerol
- TCA cycle intermediates
Fatty acids do NOT directly contribute to gluconeogenesis, but even-numbered FAs yield acetyl-CoA which can feed into fatty acid oxidation, and the glycerol from a triacylglyceride may be converted to DHAP.
What does FODMAP stand for?
- Fermentable
- Oligosaccharides
- Disaccharides
- Monosaccharides
- And
- Polyols
How do plants and fungi differ from animals in regards to fatty acids and gluconeogenesis?
They can utilise FAs in the glyoxylate cycle (shunt), which bypasses the CO2 generating steps of the TCA cycle.
In plants, glyoxysomes are the sites for this.
This essentially ‘short-circuits’ the catabolic network and shunts it back to an anabolic one.
Why DON’T you have to bypass some steps of glycolysis (i.e. NOT 1, 3, & 10) during gluconeogenesis?
These steps are close to equillibrium, and so do NOT have a highly negative ΔG / are not highly exergonic like steps 1, 3, & 10.
In other words they are readily reversible.
How many total reactions does it take to bypass steps 1, 3, & 10 of glycolysis during the gluconeogenesis pathway?
4 reactions
(These are bypasses IA, IB, II, & III)
In order to make gluconeogenesis exergonic overall, what is the overall ‘cost’?
- 4ATP
- 2GTP
- 2NADH
Identify:
The enzyme, substrate, end product, and any other important byproducts/reactants of Bypass IA during gluconeogenesis.
- Pyruvate decarboxylase
- ATP and bicarbonate are utilised to convert pyruvate into oxaloacetate.
This gives a 4C non-phosphorylated product.
Biotin (vitamin B7) is a cofactor.
Identify:
The enzyme, substrate, end product, and any other important byproducts/reactants of Bypass IB during gluconeogenesis.
- Phosphoenolpyruvate carboxykinase (PEP carboxykinase)
- Oxaloacetate is converted to phosphoenolpyruvate (PEP).
- This is coupled with GTP hydrolysis.
This generates CO2 as a byproduct.
Identify:
The enzyme, substrate, end product, and any other important byproducts/reactants of Bypass II during gluconeogenesis.
- Fructose-1,6-bisphosphatase
- Hydrolysis of phosphate ester link in fructose-1,6-bisphosphate to produce fructose-6-phosphate.
Note: NO ATP is produced though.
Reciprocal regulation compared to phosphofructokinase.
Identify:
The enzyme, substrate, end product, and any other important byproducts/reactants of Bypass III during gluconeogenesis.
- Glucose-6-phosphatase
- Dephosphorylation of glucose-6-phosphate to form glucose.
This occurs in the ER lumen and then allows it to be transported out of the cell.
G-6-phosphatase is found only in the liver and kidneys.
What is an allosteric activator of pyruvate carboxylase?
Acetyl-CoA
This is the oppposite of pyruvate kinase, which is in turn allosterically inhibited by acteyl-CoA.
What is a general rule for allosteric regulation of glycolysis and gluconeogenesis?
Molecules that activate one, tend to inhibit the other.
As they are essentially opposite processes of each other.
Where is pyruvate carboxylase located and why?
In the mitochondria, as this is where pyruvate is transported at the end of glycolysis.
What are the THREE main potential fates of pyruvate once it has entered the mitochondria after glycolysis?
- Converted to acetyl-CoA for the TCA cycle OR fatty acid synthesis.
- Converted to oxaloacetate for gluconeogenesis.
What must happen to the oxaloacetate produced in the mitochondria in order for gluconeogenesis to occur?
It must be reduced to malate, transported to the cytoplasm, and then converted back to oxaloacetate.
Why is oxaloacetate transported to the cytoplasm during gluconeogenesis?
Many of the enzymes used in this pathway are the same as glycolysis, and so are located in the cytoplasm.
Which step of gluconeogenesis burns ATP?
Step 4 (or 7 of glycolysis)
This is the opposite reaction of the one during glycolysis, which generates and ATP via phosphoglycerate kinase.
Which step of gluconeogenesis consumes/oxidises NADH?
Step 5 (or 6 of glycolysis).
This is done to reduce the substrate.
What are TWO allosteric inhibitors of fructose-1,6-bisphosphatase?
(Hint: from bypass II of gluconeogenesis).
- AMP
- Fructose-2,6-bisphosphate (strong inhibitor)
Both of these indicate low energy and build up of glycolytic substrates.
Where is glucose-6-phosphatase located?
In the ER lumen of liver and kidney cells.
It is the enzyme that catalyses the final important bypass step of gluconeogenesis
