Post on 01-Jan-2016
CHAPTER 17Gluconeogenesis
Gluconeogenesis
- The Liver and kidney can synthesize glucose from noncarbohydrate precursors such as lactate, alanine and glycerol
- Under fasting conditions, and when glycogen reserves are low,gluconeogenesis supplies almost all of the body’s glucose
2 Pyruvate + 2 NADH + 4 ATP + 2 GTP + 6 H2O + 2 H+
Glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi
Biosynthesis of glucose requires energy in the form of ATP equivalents and NADH
The placement of glycerol (from triglyceride breakdown) into glycolysis or gluconeogenesis.
DHAP can be usedfor glycolysis or gluconeogenesis
Figure 17.1: Comparison of Gluconeogenesis and Glycolysis
- NOT a complete reversal of glycolysis.
- Irreversible reactions in glycolysis cannot be utilized for gluconeogenesis
- Unique enzymatic reactions areneeded for the three irreversiblereactions of glycolysis:
hexokinasePFK-1pyruvate kinase
- All seven near equilibrium reactions of glycolysis proceed in reverse.
Figure 17.2: Carboxylation of pyruvate requires the coenzyme biotin- Bicarbonate (HOCO2
-) is first phosphorylated using ATP to make HOCO2-PO3
2-
- Biotin-enzyme + HOCO2-PO32- makes
CO2-biotin-enzyme + Pi
- CO2-biotin-enzyme + pyruvate makes biotin-enzyme + oxaloacetate
biotin
Figure 17.1: Comparison of Gluconeogenesis and glycolysis
- NOT a complete reversal of glycolysis.
- Irreversible reactions in glycolysis cannot be utilized for gluconeogenesis
- Unique enzymatic reactions areneeded for the three irreversiblereactions of glycolysis:
hexokinasePFK-1pyruvate kinase
- All seven near equilibrium reactions of glycolysis proceed in reverse.
Fructose 1,6-bisphosphatase (F1,6BPase)
- Catalyzes a metabolically irreversible reaction
- F1,6BPase is allosterically inhibited by AMP and fructose 2,6-bisphosphate (strong activator of PFK-1)
Glucose 6-phosphatase- Catalyzes a metabolically irreversible hydrolysis reaction
- In most cases, the biosynthesis ends with glucose 6-phosphate where it becomes the active substratefor pathways leading to glycogen, starch, and pentose sugar synthesis
- Glucose is an important end product when other tissue needan energy source for glycolysis. This takes place largely in the liver.
Figure 17.3: The conversion of pyruvateTo oxaloacetate.
- The conversion takes place in the mitochondrial matrix.
- Oxaloacetate is reduced to malate before transport into the cytoplasm.
- malate is then oxidized back to oxaloacetate.
GlucosePyruvate
Pyruvate translocase
Figure 17.5
Allosteric activators
Allosteric inhibitors
Allosteric activators
Allosteric inhibitors
Reciprocal regulation in the liver
Allosteric inhibitors
Allosteric inhibitorsAllosteric
activators
Allosteric activators
When glucose is abundant, glycolysis dominates
When glucose is scarce, gluconeogenesis will take over
Fructose 2,6-bisphosphate is produced by PFK-2
Recall that F-2,6-BP is a powerful activator of PFK (or PFK-1) in glycolysis
Phosphofructokinase 2 (PFK-2) synthesizes F-2,6,BP, BUT it also breaks down F-2,6-BPwhen glycolysis must be slowed. PFK-2 and FBPase2 (fructose 2,6-bisphophatase)are different enzyme activities found on the SAME protein molecule.
PFK2domain
FBPase2domain
Figure 17.7: synthesis and breakdown of fructose 2,6-bisphosphate
Insulin is secreted by the pancreas
Production of F-2,6-BPincreases
After times of Feasting
Figure 17.7: synthesis and breakdown of fructose 2,6-bisphosphate
Conc. of F-2,6-BPmust decreases
After times of Fasting
Glucagon is secreted by the pancreas
Lactate metabolism during high anaerobic activity- Glycolysis generates large amounts of lactate in active muscle
- Liver lactate dehydrogenase converts lactate to pyruvate(a substrate for gluconeogenesis)
- Glucose produced by the liver is delivered back to musclesvia the bloodstream
Figure 17.10The Cori Cycle
The interaction of glycolysis and gluconeogenesis
Assignment
Read Chapter 17Read Chapter 18