Gluconeogenesis Flashcards
Where does gluconeogenesis occur?
- occurs primarily in the liver (enzymes also in kidneys and intestinal epithelium)
- Muscles cannot participate in gluconeogenesis because they don’t have Glucose 6-phosphatase
What kind of FA can be used in gluconeogenesis?
*Even chain FA are not precursors to gluconeogenesis (acetyl CoA burned up into carbon dioxide) but odd-chain FA can because they end as propionyl CoA
What are the 3 irreversible reactions that must be bypassed for gluconeogenesis?
- Pyruvate to Phosphoenolpyruvate (PEP)
- Fructose 1,6-bisphosphate to Fructose 6-phosphate by Fructose 1,6 Bisphosphatase (dephosphorylates)
- Glucose 6-phosphate to glucose by glucose-6-phosphatase (occurs in the SER)
In pyruvate to phosphoenolpyruvate (PEP). Describe pyruvate to oxaloacetate.
- (pyruvate carboxylase)
- occurs in the MITOCHONDRIA
- requires ATP and CO2 and activated biotin (2 per glucose)
- allosterically stimulated by acetyl-CoA
- oxaloacetate can directly enter into the TCA cycle but in this case is transported to the cytosol via the malate
In pyruvate to phosphoenolpyruvate (PEP). Describe oxaloaetate to PEP.
CYTOSOL (PEP carboxykinase)
-1 GTP consumed (2 per glucose)
*PEP can be made in the mitochondria or cytosol depending on the NADH needs
-if coming from lactose then NADH already made in cytosol so PEP made in mito and then goes into cyto
-if coming from pyruvate then need to regenerate NADH so through malate intermediate
Describe Fructose 1,6-bisphosphate to Fructose 6-phosphate.
Fructose 1,6 Bisphosphatase (dephosphorylates)
-MOST REGULATED STEP IN GLUCONEOGENESIS
-Inhibited by Fructose-2,6-bisphosphate and AMP (signals an energy poor state in the cell)
-Activated by citrate and ATP
*Opposites of PFK-1
Describe regulation of Fructose Bisphosphatase-1.
Activated by cAMP cascade/glucagon and epinephrine
-Decreased levels of F26bisphosphate decrease the inhibition on FBP-1 so increases the rate of gluconeogenesis
Describe . Glucose 6-phosphate to glucose.
glucose-6-phosphatase (occurs in the SER)
-LIVER and the KIDNEYS are the only organs that release free glucose from G6P
- Energy Requiring Process
- Need 6 ATP equivalents and cytosolic NADH
What does lactate dehydrogenase do?
-Lactate to Pyruvate via lactate dehydrogenase (make NADH when going to pyruvate)
- Remember regenerating NAD+ for glycolysis is why lactate is made
- Alanine to Pyruvate via alanine aminotransferase
- AA of alanine is transferred to α-ketoglutarate to form glutamate
- coenzyme is pyridoxal phosphate (accepts and donates amino group)
Describe the cori cycle.
- reconversion of lactate to glucose by the liver
- glucose made in the liver through gluconeogenesis is converted via glycolysis in RBC and exercising muscle cells to lactate.
- Lactate then returns to the liver and is reconverted to glucose by gluconeogenesis
- makes 2 ATP in the muscle or RBC and costs 6 ATP in the liver
Describe ethanol and its role in gluconeogenesis.
- excess ethanol causes a massive increase of cytosol NADH in the liver
- this causes Pyruvate to favorable go to lactate (NADH goes to NAD+) and oxaloacetate to malate
- this causes intermediates of gluconeogenesis to be diverted to alternate pathways, resulting in decreased glucose synthesis
- this can lead to big problems when no food is eaten before drinking (lactic acidosis and coma from low blood sugar)
Describe glucagon and its role in gluconeogenesis.
- Alpha cells in the islets of Langerhans of the pancreas release glucagon during the fasting state (stimulated by decreased glucose levels)
- Increases blood glucose levels by
- stimulating the breakdown of liver glycogen (glycogenolysis)
- increasing gluconeogenesis in the liver
- in adipose tissue, glucagon activates adipose cell lipase, which degrades the stored TG into FA (serve as fuel)
- Epinephrine also serves to increase blood sugar
