gluconeogensis Flashcards
gluconeogensis occurs when blood glucose is low
starvation
not eating carbs
exercise
what hormone stimulates gluconeogensis
glucagon
what hormone inhibits gluconeogensis
insulin
what is used to make glucose
primarily AA
lactic acid
alanine
what happens prior to gluconeogensis
glycogen degradation
what are the main entry points to gluconeogensis
pyruvate
oxaloacetate
DHAP
what are the main non carb precursors
lactic acid
a keto acids from metabolism AA
glycerol
gluconeogensis pathway
pyruvate to glucose
what requires glucose
brain red blood cells testes medulla of kidney cornea of eye muscle (during high intensity exercise)
what requires the most BMR
the BRAIN
liver kidney and heart use the 60-700% of REE
glucose vs fatty acid oxidation in the brain
high O2 demand FA oxidation
superoxide
FA oxidation slow the glycolysis
lactate shuttle
where is the primary location of gluconeogensis
liver 90%
renal cortex
small intestine
how do you make gluconeogensis favorable
alternative enzymes (cytosol and mitochondria)
coupled RXNS
ATP
what are glycolysis irreversible reactions
hexokinase
phosphofructokinase
pyruvate kinase
how many reactions are reversible in glycolysis
7
First obstacle in glycolysis
phosphoenolpyruvate to pyruvate
By: pyruvate kinase (ADP to ATP)
happening in the mitochondria; Pyruvate to oxaloacetate by?
Pyruvate carboxylase
coenzyme: Biotin
(take away ATP)
where is pyruvate carboxylase present
in mitochondria of liver and kidney
also present in muscle but does not synthesize glucose (uses OAA produced as intermediate in krebs)
where is pyruvate sent
to mitochondria
whats the precursor for pyruvate carboxylase
pyruvate or alanine
what is pyruvate converted to
oxaloacetate
what is pyruvate carboxylase required enzyme
biotin
where does oxaloacetate need to get into
get into the cytosol through the malate shuttle
in the mitochondrial matrix; pyruvate is transferred to what and then that is transferred to what
pyruvate to oxaloacetate(pyruvate carboxylase) to malate (malate dehydrogenase)
in the cytosol; malate is transferred to what then to what
malate to oxaloacetate (malate dehydrogenase) to phosphoenolpyruvate (PEP carboxylase)
when is acetyl CoA produced
during FA oxidation
what does acetyl CoA stimulate
pyruvate carboxylase
what does elevated Acetyl CoA in the mitochondria signal
a need for more OAA in the cell
PEP carboxylase is dependent on what
MG+
if lactate was the precursor the reaction happens where
in the mitochondria aand PEP will be transported to the cytosol
what are two high energy compounds required to overcome the 1st obstacle
ATP-1st
GTP-2nd
what does the malate shuttle do
pyruvate or alanine precursor
provides reducing power in the cytosol for later reactions
NADH
what pathway makes glucose
gluconeogensis
lactate as a precursor
anerobic glycolysis
erythrocyte glycolysis
does lactate need a malate shuttle to go to pyruvate
no; this also happens in the cytosol and yields NADH
what is still sent to the mitochondria
pyruvate to make
pyruvate carboxylase
PEP carboxylase occur in mitochondira
PEP then transported to cytosol
what is not a substrate for gluconeogensis
leucine
what is not a irreversible step of glycolysis
phosphoglyecerate kinase
the 2nd obstacle to overcome; Fructose 1-6 bisphosphate to Fructose 6 phosphate by what
fructose 1-6 bisphosphatase and is MG+ dependent
the third obstacle to overcome; glucose to glucose 6 phosphate by
glucokinase (ATP to ADP)
glucose 6 phosphate to glucose by
glucose 6 phosphatase
MG+ dependent
releases a free P
what does not release glucose
muscle because it does not have G6P
what can release glucose
the liver because it has G6P
enzymes for glycolysis and gluconeogensis:
Glucokinase>G^P
Phosphofructokinase>Fructose 16 Bisphosphatase
Pyruvate kinase> PEP carboxylase or pyruvate carboxylase
what is gluconeogensis
it is energetically expensive
for each glucose formed from pyruvate there are
6 high energy phosphate groups:
4 ATP
2 GTP
2 NADH
what are the gluconeogenic substrates
glyerol- backbone TG
lactic acid- waste product glycolysis
a-ketoacids(more to come)
derived from glycogenic AA
pyruvate OAA a ketoglutarate
can enter into the TCA forming OAA
OAA is the direct recursor to PEP
a ketoacids
what does glycerol form the backbone for
TG
hydrolysis of TG in adipose
transported in blood to the liver
what can glycerol also be converted to
glucose
what is not a major source of glucose
glycerol
glycerol to glycerol phosphate by:
glycerol kinase
glycerol phosphate to DHAP by:
Glycerol phosphate dehydrogenase
glycolysis stimulators
glucose insulin AMP ADP NAD+ F 2 6 BP
glycolysis inhibitors
ATP NADH Glucagon Pyruvate Lactate Alanine Citrate
gluconeogenis stimulators
glucagon
Acetyl CoA
Citrate
gluconeogensis inhibitors
glucose
inulin
AMP ADP
F 2 6 BP
muscle conditions during exercise
exercise lowers ATP
muscle active pathways during exercise
glycogen breakdown Glut 4 translocation Glycolysis TAG breakdown Beta oxidation AA oxidation Krebs
liver conditions during exercise
Glucagon
High ATP
Liver active pathways during exercise
Glycogen breakdown
Gluconeogensis
Urea cycle
What is the lactic acid cycle also called
Cori cycle
What is the lactic acid cycle
Exercise: anaerobic glycolysis produces lactate
Where is lactate released from
Working muscle
And also RBC
Where is lactate transported to
The liver to become glucose
Where does the glucose return to
Returns to the muscle
Muscle glycogen to
Glucose 6P
Glucose 6P to
Krebs or lactate
Lactate to where
The liver to turn to pyruvate
Pyruvate to what
Glucose then back to the muscle
What lowers blood glucose
Exercise
What’s secreted in response to low blood glucose
Glucagon
What’s lactate released by
Muscle
Where is lactate transported to
The liver
What is stimulated by glucagon
GNG (liver)
What is lactate to pyruvate enzyme
Lactate dehydrogenase
Where is glucose released into
The blood
Where does glucose return to
The muscle
Lactate to glucose is what
GNG
What are most AA classified as
Glucogenic
A ketoacids are
Carbon skeletons of AA
What’s the primary source of glucose from GNG at rest and during fasting
A ketoacids
What is sit kited by starvation or low carbs intake
The conversion of AA into glucose
What is a AA turned into before it becomes glucose
A ketoacids
Where do a ketoacids come from
AA break down
What are the essential glucogenic AA
Think MAV H PITT Methionine Arginine Valine Histidine Phenylalanine Isoleucine Tryptophan Threonine
What happens to a ketoacids depends upon what
Energy charge
Hormones glucagon insulin
Glucose concentration
Tissue liver versus muscle
What are amino groups transferred from
Glutamate to pyruvate
Where is alanine transported to
The liver
What is alanine converted back to
Pyruvate for GNG
Where is glucose transported back to
Muscle
Alanine is a BLANK and converted to pyruvate which is a BLANK
AA
A ketoacids
Insulin inhibits what
GNG
Glucagon stimulates what
GNG LIVER
Insulin does what
B cells of the pancreas
Lowers blood sugar
Stimulate glucose utilizing pathways
Glucagon does what
A cells of the pancreas
Elevated blood sugar
Stimulates pathways that do it need glucose
What does F26BP Stimulate
Glycolysis
PFK in the liver
What does F26BP inhibit
GNG
F16BP
What decreases F26BP
Glucagon
Muscle contracts and uses ATP
Low energy charge
Lowers blood glucose
Exercise sequence part 1
Low energy charge
Stimulates glycogen breakdown Stimulate glycolysis (more lactic acid, more alanine) Stimulate krebs Stimulate glucose entry into muscle
Secrete glucagon
Exercise sequence part 2
Secrete glucagon
Stimulate glycogen breakdown in the liver
Stimulates GNG in the liver (uses lactic acid and alanine in the liver)
Inhibits glycogen synthesis in the liver
Slows down glycolysis in the liver
