Gluconeogenesis Flashcards
Gluconeogenesis means to make glucose from
Non-carbohydrate precursors
What are the precursors to gluconeogenesis
Pyruvate, lactate, propionate, glycerol, amino acids (18/20)
Where can gluconeogenesis occur
Liver
Kidney
Small intestine
GNG in kidney would be when
Increase during long term starvation
Recall which steps in glycolysis should we pay attention to
1st : glucose —hexokinase/glucokinase—>glucose 6 phosphate
3rd: fructose 6 phosphate —phophofructokinase1—>fructose 1, 6 bisphosphate
10th: Phophoenolpyruvate (PEP)—pyruvate kinase—>pyruvate
How many net ATPs do we make in glycolysis
2
1st barrier in GNG is
PYRUVATE!! —pyruvate carboxylase—> OXA —PEP carboxykinase—> PEP!!
Pyruvate to OXA characteristics
Uses 1 ATP
Biotin is its cofactor
Activated by acetyl CoA
Pyruvate carboxylase enzyme
OXA to PEP characteristics
It can either be OXA to PEP using 1 GTP
Or
OXA to Malate to OXA to PEP using 1 ATP
What can cross the membrane and is made from pyruvate and why is that significant
PEP and Malate
Significant because pyruvate wants to get out of the mito to do GNG in the cytosol
The malate shuttle during GNG shuttles _____ so there is energy to make glucose
NADH
When comparing glycolysis and GNG, specifically looking at PEP and pyruvate what is a key difference
Glycolysis utilizes 1 enzyme, pyruvate kinase
It takes 2 molecules of PEP and makes 2 molecules of pyruvate: making 2 ATP
GNG utilizes 2 enzymes, pyruvate carboxylase and PEP carboxykinase
It uses 4 ATP when taking pyruvate and making PEP
Compare glycolysis and GNG PEP/pyruvate ATP
Glycolysis makes 2 ATP
GNG uses 4 ATP
The 2nd and 3rd barriers of GNG are
Fructose 1,6 —fructose 1,6 bisphosphatase—> Fructose 6 phosphate
Glucose 6 phosphate —-glucose 6 phosphatase—>glucose
Location of glycolysis vs GNG
Glycolysis = cytoplasm
GNG = cytoplasm and mitochondria
Energy of glycolysis vs GNG
Glycolysis = 2 ATP generated
GNG = 6 ATP consumed
GNG is very
Energy consuming
Pyruvate and lactate structural comparison
They have the same structure except lactate is reduced
Pyruvate to lactate enzyme is ___
Lactate dehydrogenase
Pyruvate to lactate is a ____ reaction that uses _____ for energy/or to make energy
Reversible
NADH<—>NAD+
Lactate to pyruvate is driven by
NADH concentration
Structural difference between alanine and pyruvate
Alanine has an amino group
Alanine to pyruvate is a ____ reaction
Reversible
Alanine + ______ <—> pyruvate + _____
α - ketoglutarate
Glutamate
Cori cycle aka
Glucose - lactate cycle
ATP generation and consumption of cori cycle
6 ATP used in liver for GNG
2 ATP were created in RBC
Key point of glucose alanine cycle
Brings carbon to liver for GNG
ASLO
Brings ammonia for urea synthesis
AA that can be used in GNG are called
Gluconeogenic
AA that cannot be used in GNG are called
Ketogenic
What are the AA that cannot be used in GNG
Lysine and Leucine; they are ketogenic AA
Which AA are gluconeogenic and ketogenic
Phenylalanine
Tyrptophan
Phenylalanine
And
Isoleucine
Think “TP,PI, TP, PI” IV chant
What is more important than the process of GNG
The REGULATION of GNG
Where is the carbon backbone of GNG from
The 5 precursors
Pussys Like Good Pounding And Ass
Pussy’s=pyruvate
Like=lactate
Good=glycerol
Pounding=propionate
And Ass=amino acids
Where does energy come from in GNG
Break down fatty acids
this makes acetyl CoA
Hormones like ______ communicate everything needed for GNG
Insulin and glucagon
Our liver glycogen storage lasts for
Less than a day
GNG will start before _____ are depleted
Glycogen stores
____ is important in regulating GNG
Pyruvate
Pyruvate can either be turned into ____ or _____
Acetyl CoA
OAA
To up regulate GNG what should pyruvate turn into
OAA
When regulating pyruvate and your end goal is to make PEP what are the paths to get there
1.Pyruvate to OAA to PEP
2.pyruvate to OAA to Malate to OAA to PEP
- Pyruvate to OAA to ASP to OAA to PEP
When you have enough NADH in the cytosol what process will GNG follow
pyruvate to OAA straight to PEP allll in the mitochondria
If you have low NADH in the cytosol what path will GNG follow
Pyruvate to OAA to malate (shuttle out of mito to cytosol) to OAA to PEP
_____ is inactive without Acetyl CoA
Pyruvate carboxylase
When you see ATP or CO2 you know ____ is used as well
Biotin
High ATP _____ fructose 1,6 bisphosphatase 1 and they ______ phosphofructokinase 1
Activate
Inactivate
Because if there is high ATP we do not need glycolysis to happen
High _____ and similarly high ______, increase phophofructokinase 1 and this drives glycolysis forward
AMP
Fructose 2,6 bisphosphate
How do insulin and glucagon manipulate cells for glycolysis and GNG
It utilizes fructose 2,6 bisphosphate
fructose 2,6 bisphosphate is like an
On/off switch for glycolysis
When fructose 2,6 bisphosphate is high that means ___
It favors glycolysis
It is “on”
Activate PFK1
And INACTIVATE fructose 1,6 bisphosphatase 1
When fructose 2,6 bisphosphate is low that means ___
It favors gluconeogenesis
It is “off”
No glycolysis
Activate fructose 1,6 bisphosphatase 1
INACTIVATE PFK1
Which step of GNG is the rate limiting step
Fructose1,6bisphosphate to fructose 6 phosphate
What kind of FA are used to be turned into glucose
Odd chain
odd chain FA path
Odd chain FA to propionate to OAA to PEP to glucose
Where does the carbon backbone come from in GNG
Pyruvate, lactate, glycerol, propionate, AA
Where does the energy come from to help GNG continue forward
Fatty acid catabolism (which makes Acetly CoA) supports GNG
What are the big regulators of GNG and what are they classified as
Insulin and glucagon
