Gluconeogenesis Flashcards
What purpose does gluconeogenesis serve?
Converts pyruvate and related 3 & 4 carbon compounds to glucose when supplies are low.
T or F: Fatty acids can be used to synthesize glucose
F
What makes a compound glucogenic?
Net synthesis. Conservation of all carbons in a metabolic pathway.
What cellular compartments are involved in gluconeogenesis?
Mitochondrial
Cytosolic
ER (lumenal side)
What is the overall reaction of gluconeogenesis?
2 pyruvate + 4ATP + 2GTP + NADH + 6water —-> Glucose + 4ADP + 2GDP + 6Pi + 2(NAD+) + 2(H+)
Gluconeogenesis is basically the reversal of glycolysis with three major exceptions. What are those?
The three control steps in glycolysis are bypassed:
- Pyruvate kinase bypassed by Pyruvate carboxylase & PEPCK
- PFK-1 bypassed by Fructose-1,6-bisphosphatase
- Hexokinase bypassed by Glucose-6-phosphatase
What are the 4 unique reactions of gluconeogenesis?
Pyruvate carboxylase
PEPCK (phosphoenolpyruvate carboxykinase)
Fructose-1,6-bisphosphatase
Glucose-6-phosphatase
What role does biotin play in pyruvate carboxylase?
Pyruvate carboxylase converts pyruvate to oxaloacetate during gluconeogenesis where biotin, a common CO2 carrier, acts as a prosthetic group.
Pyruvate carboxylase activity requires what?
AcCoA which comes from pyruvate
How is OAA (oxaloacetate) moved into the cytosol during gluconeogenesis?
Malate dehydrogenase
Describe the rolls of the two malate dehydrogenase isozymes.
Mitochondrial malate dehydrogenase uses NADH to reduce OAA to malate so it can be transported into the cytosol, then cytosolic malate dehydrogenase reoxidizes malate to get OAA and NADH.
What is another pathway to move OAA into the cytosol besides malate dehydrogenase?
Aspartate aminotransferase which is utilized in the urea cycle.
Note: It does not transfer NADH into cytosol.
Describe the rolls of the two PEPCK isozymes?
The main differences are what has to be transported out.
Mitochondrial PEPCK decarboxylates oxaloacetate to PEP directly in mitochondria, then PEP is transported out.
Cytosolic PEPCK decarboxylates OAA to facilitate PEP formation. Transport of NADH to cytosol important for other reactions.
What is the phosphoryl requirement for PEPCK?
GTP
Which enzyme involved in gluconeogenesis reverses the hexokinase reaction from glycolysis?
Glucose-6-phosphatase
PEPCK, Fructose-1,6-bisphosphatase and glucose-6-phosphatase all require what cofactor for activation?
Mg2+
What makes a compound glucogenic?
Conservation of all carbons through the TCA cycle.
Anything AFTER the a-ketogluterate dehydrogenase reaction is glucogenic.
Why is regulating glycolysis and gluconeogenesis so important?
To avoid futile cycles
How does substrate availability affect regulation of gluconeogenesis and glycolysis?
AcCoA and pyruvate are needed to initiate/inactivate these metabolic processes.
How does glucagon affect enzymatic activity?
Glucagon has a positive effect on gluconeogenic enzymes because it is a starved state hormone. This means it would have a negative effect on PFK-1 & pyruvate kinase.
How does insulin affect enzymatic activity?
Insulin has a positive effect on PFK-1 & pyruvate kinase while having a negative effect on PEPCK because insulin is a “fed state” hormone.
How is fructose-1,6-bisphosphatase allosterically regulated?
Positive effectors: Citrate
Negative effectors: AMP, F2,6-bisphosphate (stimulates glycolysis, but inhibits gluconeogenesis)
Phosphorylation of fructose-6-phosphate is catalyzed by
PFK-2 and Fructose-2,6-bisphosphatase.
The balance of PFK-2 and F26-bisphosphatase activities determine concentration of F26-bisphosphate, all regulated by glucagon & insulin.
What are the positive and negative effectors of pyruvate carboxylase?
Positive: AcCoA (apart of pyruvate)
Negative: ADP
Provide three sources of the carbons needed to make glucose.
3 carbon compounds: Lactate, pyruvate, glycerol
What is the primary difference between cytosolic and mitochondrial forms of PEPCK?
Mitochondrial PEPCK is utilized when lactate is the precursor for glucose synthesis & cytosolic PEPCK is utilized when pyruvate is the precursor for glucose synthesis.
