Gluconeogenesis Flashcards
net equation for gluconeogenesis
2 pyruvates + 4 ATP + 2 GTP + 2 NADH —-> 1 glucose + 4 ADP + 2 GDP + 6 Pi+ 2 NAD+
location for gluconeogenesis
liver cells & renal cortex cells
why are renal medulla largely anaerobic? what fuel do they use?
they don’t get good blood supply (blood delivers O2). glucose. renal medulla cells are always making a lot of lactate
when does gluconeogenesis in the liver increase?
- the fasting state
2. in a high protein meal
why is it important that gluconeogenesis and glycolysis aren’t exact reversals of one another?
it gives the cell tremendous control to be a glucose user in the fed state (glycolysis) and a glucose producer in the fasting state (gluconeogenesis)
where is blood sugar coming from in the fed state?
your meal (mostly)
where is blood sugar coming from in the fasting state?
First, hepatic gycogenolysis (for about 1.5 days)
Not long after glycogenolysis begins contributing, so does gluconeogenesis
Gluconeogenesis becomes the sole provider until the person eats again (up to about 40 days)
name the enzyme that catalyzes the rxn from pyruvate to oxaloacetate
pyruvate carboxylase
what cells have pyruvate carboxylase
liver cells and adipocytes
catalytic cofactor for pyruvate carboxylase
biotin
location for the pyruvate carboxylase rxn
mitochondrial matrix
pyruvate carboxylase is allosterically activated by __________
acetyl coA (coming from glucose in the fed state and beta-oxidation of fatty acids in the fasting state)
liver cell’s favorite fuel
fatty acids (carried from adipocytes by albumin)
name the enzyme that catalyzes the rxn from oxaloacetate to PEP
Phosphoenolpyruvate carboxykinase (PEPCK)
why is the PEPCK rxn improtant
changes OAA into something that can get out of the mitochondrial matrix (PEP
high energy phosphate donor in the PEPCK rxn
GTP
location for the PEPCK rxn
cytosol
name the enzyme that turns PEP ——> 2-phosphoglycerate
enolase
name the enzyme that turns 2-phosphoglycerate ——> 3-phosphoglycerate
phosphoglyceromutase
name the enzyme that turns 3-phosphoglycerate ——> 1,3-bisphosphoglycerate
phsophoglycerate kinase
what enzyme catalyzes the rxn from 1,3 bisphosphoglycerate ——–> glyceraldehyde-3-phosphate?
what does it cost?
how many times does it happen?
glyceraldehyde-3-phosphate dehydrogenase
- costs NADH
- happens twice
name the fate of the two glyceraldehyde-3-phosphate molecules produced in gluconeogenesis
1 gets converted to DHAP (dihydroxyacetone phosphate) using triose phosphate isomerase
1 gets converted to fructose-1,6-phosphate using aldolase
what enzyme catalyzes the rxn from fructose-1,6-bisphosphate —-> fructose-6-phosphate?
fructose-1,6-bisphosphatase
- only happens once
- irreversible
- hydrolysis of a phosphoester bond
what enzyme catalyzes the rxn from fructose-6-phosphate —-> glucose-6-phosphate?
phosphoglucose isomerase
- change from a ketose to an aldose
what enzyme catalyzes rxn from glucose-6-phosphate —-> glucose?
glucose-6-phosphatase
- hydrolysis rxn
- allows liver cells to have exportable glucose
location for the glucose-6-phosphatase rxn
endoplasmic reticulum
how does oxaloacetate formed in the mitochondrial matrix get into the cytosol for continuation of gluconeogenesis?
- can change to malate via the malate dehydrogenase rxn (the major option)
- can change to aspartate via an amino transferase rxn
what’s the major rxn in the conversion of OAA into something that can go into the cytosol for gluconeogenesis? why?
malate dehydrogenase rxn
b/c the liver’s fave fuel is fatty acids, beta-oxidation of fatty acids in the fasting state produces a lot of NADH which pushes the malate dehydrogenase rxn further towards the direction where OAA (ketone) —> malate (secondary alcohol)
locations for the malate dehydrogenase rxns
mitochondrial matrix & cytosol
reducing agent for the malate dehydrogenase rxn
NADH
name the enzyme:
oxaloacetate + glutamate ——–> aspartate + alpha-KG
aspartate transaminase rxn (AST)
catalytic cofactor for transaminases?
pyridoxal phosphate (PLP), derived from vitamin B6 (pyroxin)
what does it mean if ALT or AST levels are too high in a pt’s tests?
sign of liver disease
non-carbohydrate precursors for the liver’s synthesis of glucose
alanines
glycerol
lactate
what enzyme catalyzes the rxn from lactate ——> pyruvate?
oxidizing agent?
reactants?
products?
lactate dehydrogenase rxn
oxidizing agent: NAD+
reactants: lactate + NAD+
products: pyruvate + NADH + H+
name the enzyme:
alanine + alpha-KG <—–> pyruvate + glutamate
alanine transaminase rxn
name the enzyme:
glycerol ——-> glycerol-3-phosphate
what does it require?
glycerol kinase
- requires ATP
what cells have glycerol kinase & why?
liver cells; to be able to use glycerol where other cells can’t (to make glucose)
name the enzyme:
glycerol-3-phosphate —-> dihydroxyacetone phosphate (DHAP)
what is required?
glycerol-3-phosphate dehydrogenase
- NAD+ required
name the enzyme:
pyruvate ——-> acetyl group of acetyl CoA
pyruvate dehydrogenase
- unfavorable for gluconeogenesis
inhibitors of the pyruvate dehydrogenase rxn
enzyme action: pyruvate —-> acetyl group of acetyl coA
acetyl CoA & NADH
- activate PDC-kinase which turns off PDC by catalyzing its phosphorylation
activator of pyruvate carboxylase rxn
enzyme action: pyruvate —-> OAA
acetyl CoA (comes from beta-oxidation of fatty acids from adipocytes carried by albumin)
inhibitors of the pyruvate kinase rxn
action: PEP —-> pyruvate
alanines
ATP
protein kinase A (catalyzes phosphorylation of pyruvate kinase)
what enzymes of gluconeogenesis are inducible?
PEPCK
fructose-1,6-bisphosphatase
glucose-6-phosphatase
what factors reciprocally control PFK-1 and fructose-1,6-bisphosphatase?
concentration of fructose-2,6-bisphosphate
- activator of PFK-1 for glycolysis (from fructose-6-phosphate —–> fructose-1,6-bisphosphate)
- inhibitor of fructose-1,6-bisphosphatase for gluconeogenesis (from fructose-1,6-bisphosphate —–> fructose-6-P)
how do glucagon signal lead to phosphorylation of pyruvate kinase?
- glucagon binds to glucagon receptor on outside of liver cell
- receptor changes shape
- heterotrimeric G-protein feels shape change
- alpha subunit drops a GDP and picks up a GTP
- shape change activates adenylate cyclase
- cAMP concentration increases and becomes second messenger
- activates protein kinase A
- catalyzes phosphorylation of pyruvate kinase
how do glucagon signals lead to increased PEPCK synthesis?
- glucagon binds to glucagon receptor on outside of liver cell
- receptor changes shape
- heterotrimeric G-protein feels shape change
- alpha-subunit drops GDP and picks up GTP
- shape change activates adenylate cyclase
- cAMP concentration increases, becomes second messenger
- activates protein kinase A
- protein kinase A catalyzes phosphorylation of CRE (cAMP response element) binding protein
- transcription factor changes shape
- increases transcription of gene which codes for PEPCK
how do glucocorticoid signals for cortisol stimulate PEPCK synthesis?
- cortisol binds to intracellular glucocorticoid receptor in the cytosol
- GR begins to dimerize
- GRs go into nucleus and bind to gene that code for PEPCK in the glucocorticoid response element (GRE)
- gene that codes for PEPCK gets transcribed more
why is gluconeogenesis dependent on beta-oxidation of fatty acids?
beta oxidation of fatty acids from adipocytes carried by albumin to liver cells produces:
- NADH
- FADH2
- Acetyl CoA
While fatty acids are not a source of carbons for gluconeogenesis, they’re still important because…
- liver cells need ATP (from acetyl Coa and from the electrons being sent to the ETC by the FAD2H and NADH)
- NADH inhibits pyruvate dehydrogenase rxn and converts OAA –> malate in the mito matrix
- acetyl CoA is worth ATP, inhibits pyruvate dehydrogenase, and activates pyruvate carboxylase
