gluconeogenesis and ketogenesis Flashcards
role of the liver as an energy provider
- maintains blood glucose levels through glycogen breakdown and gluconeogenesis
-produces ketone bodies through ketogenesis
the liver produces glucose through gluconeogensis through
carbon sources: lactate, amino acids, glycerol, fructose
energy source: ATP from fatty acid oxidation
many enzymes for glycolysis are also used for gluconeogenesis except for _______
irreversible steps
______ is a TCA intermediate; the TCA pool is used to make glucose
oxaloacetate
the step catalyzed by _________ is the rate-limiting step for gluconeogenesis
phophoenolypyruvate (PEP) carboxykinase
the transport of oxaloacetate from mitochondria occurs through ____ or ______
aspartate or malate shuttle
3 irreversible steps
-gluconeogenesis needs different enzymes at the steps corresponding to the 3 irreversible steps of glycolysis
-the pairs of glycolytic and gluconeogenic enzymes make futile cycles; require tight regulation
-glucose 6 phosphate is expressed only in the liver
-6 phosphofructo 1 kinase and pyruvate kinase are regulated allosterically
comparison of glycolysis and gluconeogenesis
-conversion of glucose to pyruvate yields 7 ATP equivalent
-synthesis of glucose from pyruvate requires 11 ATP equivalent
glucokinase
-liver cells have glucokinase instead of hexokinase for glycolysis
-glucokinase utilizes glucose only when the concentration is high
-futile cycle formed by glucokinase and glucose 6 phoshayase keeps the cellular glucose concentration high
activation of gluconeogenesis is largely accomplished in large part by
-inhibition of glycolysis
-ATP inhibits 6 phosphofructo 1 kinase and pyruvate kinase
_____ occurs hand in hand with gluconeogenesis, promoting glucose synthesis
-fatty acid oxidation
-supplying ATP –> used in gluconeogenesis
-increases acteyl CoA –> inactivation of pyruvate dehyrogenase and activation of pyruvate carboxylase
increase in oxaloactate and acetyl CoA results in increase in ____
-citrate, which is a negative allosteric regulator of 6 phosphate 1 kinase
alcohol and gluconeogenesis
-oxidation of ethanol by the liver depletes NAD+ in the cytosol
-excess NADH converts pyruvate to lactate
-gluconeogenesis by the liver is suppressed
-may cause hypoglycemia and alcohol induced lactic acidosis
-problem is more severe when glycogen storage in the liver is depleted under malnutrition or strenuous exercise
pentose phosphate pathway
-produces NADPH, the major reducing equivalent for biosynthesis
-produces ribose 5 phosphate, which is used for DNA and RNA synthesis
-first step is the rate-limiting step and the commitment step for pentose phosphate pathway
glucose 6 phosphate has many fates in the cells
-glycolysis
-glycogen synthesis
-pentose phosphate pathway
-glucose production (only in liver)
NADH
source: glycolysis, TCA cycle, fatty acid oxidation
uses: generation of ATP by oxidative phosphorylation
NADPH
source: pentose phosphate pathway
uses: reducing cofactor in anabolic reactions
ketone bodies
-water soluble products from lipid oxidation (acetyl CoA)
-produced mostly by the liver during prolonged fasting or ketogenic diet
-concentration can be > 3mM in blood
-ketogenesis reduces the need for gluconeogenesis (reducing protein waste)
-utilized by many tissues as a fuel
synthesis of ketone bodies
-occurs in the mitochondria
-HMG CoA synthase is expressed at high level in the mitochondria during prolonged fasting
ratio of acetoacetic acid to B-hydroxybutyric acid is dependent on the ratio of ___________ in liver mitochondia
NAD+/NADH
the spontaneous production of ____ from acetoacetic acid is significant only when the concentration of ketone bodies is high
acetone
utilization of ketone bodies
-converted to acetyl CoA in the mitochondria of nonhepatic tissues
-reducing equivalent in B-hydroxybutyric acid is harvested as NADH
-Acetyl CoA is used as fuel in the TCA cycle
______ is more versatile energy source than fatty acids
glucose
glucose can be used to generate ATP through ______ in case of insufficient O2 supply
anaerobic fermentation
when O2 is sufficient
fatty acids and ketone bodies are preferred to glucose
active fatty acid oxidation increases citrate which ______ glycolysis
suppresses
the regulation mechanism is analogous to the switching between ____ and _____ in the liver
glycolysis and gluconeogenesis
ketoacidosis
-occurs mostly in type 1 diabetic patients
-low insulin levels promote lipolysis in the adipose tissues
-the production of an excess amount of ketone bodies drops the pH level of the blood
-medical emergency
