Lecture 21: Gluconeogenesis Flashcards
Role of Liver as energy provider
-maintain blood glucose by glycogen breakdown and gluconeogenesis
-produce ketone bodies in ketogenesis
*Carbon sources of gluconeogenesis
-lactate
-amino acids
-glycerol
-fructose
Energy source of gluconeogenesis
ATP from FATTY acid OXIDATION
*Rate-limiting step of gluconeogenesis
-step catalyzed by pep carboxykinase
Gluconeogenesis
-liver producing glucose
-many enzymes reused except irreversible steps
Gluconeogenesis reaction
lactate to pyruvate to oxaloacetate (occurs in TCA cycle) to phosphoenolpyruvate
Oxaloacetate in gluconeogensis
-comes from TCA cycle
-transported from mitochondria via aspartate/malate shuttle
*Futile cycle regulation glycolysis vs gluconeogenesis
-G6Pase expressed ONLY in liver
-6-phosphofructokinase and pyruvate kinase regulated ALLOSTERICALLY
Glucose to pyruvate ATP
-YIELDs 7 ATP
Pyruvate to glucose ATP
-NEEDS 11 ATP
Glucokinase
-replaces hexokinase in the liver
-uses glucose only when there is a LOT
-futile system with G6Pase keeps blood sugar up
Activation of Gluconeogenesis
-inhibition of glycolysis
-fatty acid oxidation
-increase in citrate
Inhibition of glycolysis
ATP inhbits 6phosphofructokinase and pyruvate kinase
Fatty Acid oxidation
-supplies ATP for gluconeogenesis
-increase acetyl CoA that INactivates pyruvate DEHYDrogenase and ACTIVATES pyruvate CARBoxylase
Increase in citrate
-caused by increase in oxaloacetate and acetyl CoA
-negative allosteric regulator of 6phosphofuctokinase
CHART SLIDE 9
LIKE ACTUALLY LOOK
Alcohol and gluconeogenesis
-oxidation of ethanol by liver depletes NAD+
-excess NADH converts pyruvate to lactate
-gluconeogenesis by liver is suppressed
Problems of alcohol
-hypoglycemia
-lactic acidosis
-problem more severe when glycogen storage in liver is depleted (malnutrition/exercise)
Pentose Phosphate Pathway
-produces NADPH
-produces ribose-5-phosphate used for DNA synthesis
Pentose Pathway rate-limiting AND commintment step
-first step
G6P fate
-glycolysis
-glycogen synthesis
-PPP
-glucose production in liver
NADH sources
-glycolysis
-TCA
-fatty acid oxidation
NADH uses
-generation of ATP by oxidative phosphorylation
NADPH sources
-PPP
NADPH uses
-anabolic reactions
Ketone bodies
-water soluble products of lipid oxidation (acetyl CoA)
-produced by liver during fasting
-reduces need for gluconeogenesis
-reduces protein wasting
-used by brain and skeletal muscles as fuel
Ketone body synthesis
-mitochondria
-HMG-CoA synthase expressed at high levels during fasting
- 2 acetyl CoA (C2) –> acetoacetyl CoA
- Acetoacetyl CoA + acetyl CoA –HMGsynthase–> HMG-CoA (C6)
ratio of acetoacetic acid to B-hydroxybutyric acid
-dependent on ration of NAD+/NADH in liver mitochondria
ketoacidosis
-high concentration of ketone bodies
-leads to spontaneous production of acetone from acetoacetic acid
Using ketone bodies
-converted to acetyl CoA in mitochondria outside liver
-reducing equivalent in B-hydroxybutyric acid harvested as NADH
-acetyl CoA used as fuel in TCA cycle
B-hydroxybutyric acid to acetyl-CoA
-to acetoacetic acid first
-then to acetoacetyl CoA
= 2 acetyl CoA
Energy sources for physical activities
-fatty acid and ketone bodies are preferred to glucose when O2 is sufficient
Fatty Acid oxidation increases Citrate
-suppresses glycolysis
-similar to switching between glycolysis and gluconeogenesis
Slide 18
come on u got this king
Ketoacidosis
-mostly in type I diabetics
-low insulin promots lipolysis in adipose tissue
-production of lots of ketone bodies LOWERS blood pH
-medical emergency
When the blood glucose levels are low, which of the following reactions is suppressed in the liver?
-Conversion of fatty acids to acetyl CoA
-Conversion of pyruvate to acetyl CoA
-Conversion of pyruvate to oxaloacetate
-Conversion of oxaloacetate to phosphoenolpyruvate
-Conversion of lactate to pyruvate
Conversion of pyruvate to acetyl CoA
