Gluconeogenesis Flashcards
What precursors can be used for gluconeogenesis?
Lactate, pyruvate, glycerol, amino acids, etc.
Where does gluconeogenesis occur?
Primarily in liver
Why is gluconeogenesis essential?
Because brain and RBC’s require glucose and cannot synthesize it on their own
After a meal what is the source of blood glucose?
Digested food
After 2-3 hours fasting what is source of glucose?
Glycogenolysis
After prolonged fasting what is the source of glucose?
Gluconeogenesis
(393) During exercise what is the source of glucose?
(393) Glycogenolysis and gluconeogenesis
(395) What glycolytic enzymes does gluconeogenesis bypass
Glucokinase, PFK1, pyruvate kinase
What enzymes are used to bypass the glycolytic reactions?
Pyruvate carboxylase, PEPCK, F-1,6-bipshosphatase, G6Pase
What does pyruvate to oxaloacetate reaction require?
Pyruvate carboxylase, Biotin, active in both fed and fasting state
What activates pyruvate carboxylase?
Acetyl Coa (means TCA is backed up and we should synthesize glucose)
(399) What does PEPCK require to convert oxaloacetate into PEP?
GTP
The steps between PEP and G3P occurs where? And what is the reaction pathways for these steps?
Cytosol, reverse of glycolysis
What are three ways gluconeogenesis is regulated?
Amount of substrate, amount of enzyme, activity of enzyme
What activates pyruvate carboxylase?
Acetyl CoA
(403) What inhibits PDH?
Acetyl CoA
Describe regulation of the amount of pepck?
Glucagon /epinephrine signal adenylate cyclasecAMPPKAtranscription factors more PEPCK
What inhibits pyruvate kinase?
cAMP and PKA (opposite to PEPCK since this is a glycolytic vs. gluconeogenitic enzyme)
What activates F16Bpase?
low F-2,6 BP
(407) What is the energetic requirement for gluconeogenesis?
4 ATP, 2 GTP, and 2 NADH
(394) What cellular locations does gluconeogenesis occur?
Pyruvate carboxylase in mitochondria, PEPCK in between mitochondria and cytosol, rest is in cytosol except for G6Pase which is in ER
Glycolysis is to Glucokinase as gluconeogenesis is to ___________?
Glucose -6- Phosphatase
Glycolysis is to Phosphofructokinase as Gluconeogenesis is to _____________?
Fructose Bis-Phosphatase
Glysolysis is to Pyruvate kinase as gluconeogenesis is to ____________?
PEP Carboxykinase
Glysolysis is to Pyruvate dehydrogenase as gluconeogenesis is to ___________?
Pyruvate carboxylase
What is the pathway for synthesizing glucose from lactate, pyruvate, glycerol, amino acids?
gluconeogenesis
What is the only source of of glucose in the fasting state?
gluconeogenesis
Why is gluconeogenesis essential in the brain and RBCs?
They require glucose and cannot synthesize glucose on their own because fatty acids cannot cross blood brain barrier
Why can gluconeogenesis occur only in the liver and long starvation occur in the kidney?
only tissues that express G-6-Pase
After 2-3 hours of fasting, what allows for glucose?
glycogen is degraded to glucose via glycogenolysis
During exercise, glucose is supplied to the blood by what?
gluconeogenesis and glycogenesis
What is the relationship of glycogenolysis and gluconeogenesis after a meal?
glycogenolysis occurs quickly and gluconeogenesis occurs more gradually
What pathway is used to recycle carbons during glycolysis and in the Cori and Alanine cycles?
gluconeogenesis
What is the end product of RBC in glycolysis?
lactate
What are the 3 major carbon sources for gluconeogenesis?
lactate (pyruvate), amino acids (alanine), glycerol (adipocyte lipolysis)
What irreversible enzymes of glycolysis must be bypassed in order for gluconeogenesis to occur?
GK, PFK-1, pyruvate kinase
What are the 4 irreversible enzymes that bypass the same as glycolysis?
pyruvate carboxylase, PEPCK, FBPase-1, G6Pase
In relation to GK, PFK-1, and pyruvate kinase, when does gluconeogenesis occur? What is the result?
- low activity of each of the molecules
- minimizes glycolysis and low pyruvate dehydrogenase activity while saving pyruvate for gluconeogenesis
What are the key reactions or regulatory steps of gluconeogenesis?
- pyruvate to PEP
- F-1,6-bisphosphate to Fru-6-phosphate
- G-6-P to glucose
Describe the conversion to pyruvate to PEP via specific enzymes involved which occurs in the liver
- Pyruvate => OAA via PC (ATP requiring)
- OAA uses the malate/aspartate shuttle to cross inner Mt membrane
- OAA => decarboxylated by PEPCK (GTP requiring)
- Phosphoenolpyruvate => fru-1,6-bispho
Describe the conversion of Fru-1,6-biphos to Fru-6-phos
- Fructose 1,6 biphos => fru-6 phos via 1,6-biphosphatase
2. Fru-6-P converted to G-6-P
Describe conversion from G-6-P to glucose
- G-6-P produces FREE GLUCOSE via G-6-Pase
2. G-6-Pase involved in both gluconeogenesis and glycogenolysis
T/F Conversion from pyruvate to PEP occurs in the cytosol only
False, PC enzyme is located in the Mt so must occur there but PEPCK can be located in the Mt and cytosol
Where are the fatty acids oxidized and where are they released from? What molecules are they oxidized to?
Released from adipose tissue that travel to the liver where they under go Beta oxidation to acetyl CoA, NADH, ATP
What are the effects of Acetyl CoA in the first step of gluconeogenesis?
- activates PC
2. inhibits pyruvate dehydrogenase
Why must pyruvate dehydrogenase be inhibited?
Pyruvate would be used in the TCA cycle thus disrupting the generation of PEP
Describe the relationship of Fru-1,6-Bisphos, PFK-1
When F-2,6-P is low, PFK-1 is less active and F-1,6-biphos is more active
Describe the domains of PFK-2
kinase domain: F6-P => F-2,6-P
phosphatase domain: F-2,6-BP hydrolyzed to F-6-P
How is pyruvate kinase inactivated?
Glucagon via cAMP and PKA causes pyruvate kinase to be phosphorylated
The synthesis of F-2,6-P is controlled by what? Describe the relationships
insulin and glucagon
Increase glucagon and increase cAMP then PKA is activated => gluconeogenesis promoted
increase insulin => decrease cAMP => dephosphorylation of PFK2 => glycolysis promotion
T/F GK is inactive during gluconeogenesis, explain
True, high Km for glucose so since glucose concentrations are low then the GK is not needed
What supplies energy for gluconeogenesis?
Fatty acid oxidation
Oxidation of lactate
Describe the relationship of insulin in the liver, muscle, adipose
liver: insulin promotes storage of glucose as glycogen and prod. of TAG
Muscle: insulin stimulates transport of glucose into cell and glycogen synthesis
Adipose: insulin stimulates transport of glucose into adipose and TAG production
What is involved in the blood glucose levels in the fasting state?
change in insulin and glucagon levels, stimulation of glycogenolysis and gluconeogenesis
