Chapter 10- gluconeogenisis Flashcards
What are the three primary pathways for anabolic carbohydrate metabolism?
Gluconeogenisis
Pentose phosphate pathway
Glycogen degredation and synthesis
What does glycolysis do?
Convert glucose to pyruvate
What is gluconeogenesis?
Synthesis of glucose from non-carbohydrate precursors
TF: Gluconeogenesis is a reversal of glycolysis
False
There were 3 irreversible reactions in glycolysis so we cannot reverse the reactions
What are the major precursors for gluconeogenesis?
Lactate
Glucogenic amino acids
Glycerol
Where are the major sites of gluconeogenisis?
liver and kidney
What is gluconeogenesis used to do?
Maintain blood glucose levels in order to provide glucose to the BRAIN and red blood cells
What kind of reactions are used in both glycolysis and gluconeogenesis?
The reversible reactions
TF: ATP is made in gluconeogenesis?
FALSE
no ATP is generated
Why is gluconeogenesis and glycolysis differentially regulated?
To prevent a futile cycle
SO anabolic and catabolic reactions do not happen at same time
What steps in glycolysis must be bypassed in gluconeogenesis?
Reactions 1,3 and 10
the irreversible steps
Where do the first gluconeogenic steps travel through
the mitochondria
After glycolysis where does pyruvate go?
Into the mitochondria
What cannot escape out of the membrane of mitochondria?
Oxaloacetate
Can be converted to PEP or malate to allow for transport to cytosol for gluconeogenesis
What is needed for gluconeogenesis to occur?
Increased cytosolic levels of NADH
What does pyruvate carboxylase do and what is its prosthetic group?
Converts pyruvate to oxaloacetate
Biotin is the prosthetic groups (carries activated CO2)
What does pyruvate carboxylase use to convert pyruvate to oxaloacetate?
ATP and HCO3-
Why is pyruvate converted to oxaloacetate?
To keep it from leaving the mitochondria
What does phosphoenolpytuvate carboxykinase do?
Coverts oxaloacetate to PEP
CO2 is removed/ phosphate is added
Oxaloacetate is decarboxylated and phosphorylated
What is the phosphoryl donor for Phosphoenolpyruvate carboxykinase?
GTP
How is Oxaloacetate moved outside of the mitochondria?
It is reduced to malate which exits the mitochondria into the cytosol
Remember oxaloacetate cannot cross mitochondrial membrane
How is Oxaloacetate moved outside of the mitochondria?
It is reduced to malate which exits the mitochondria into the cytosol
Remember oxaloacetate cannot cross mitochondrial membrane
When would oxaloacetate be utilized?
In the Kreb’s cycle
Gluconeogenesis but needs to be converted to PEP to go to cytosol
What needs to happen for Glyceraldehyde 3 P production?
NADH equivalents need to move from inner mitochondrial matrix to the cytosol
How is NADH produced for gluconeogenesis?
Malate is oxidized back to oxaloacetate by malate dehydrogenase and then NADH is produced in the cytosol
Where is lactic acid produced from anaerobic metabolism?
In muscle cells and from cells lacking a mitochondria
TF: When lactate is the precursor for gluconeogenesis and pyruvate is the precursor, both use the same PEP carboxykinase from oxaloacetate
FALSE
Each pathway uses a different PEP carboxykinase (mitochondrial for lactate pathway and cytosolic for pyruvate pathway)
What does the cori cycle do?
Provides glucose to muscle cells during exercise
Converts lactate to glucose
Where is lactate produced by anaerobic glycolysis?
In muscle cells
Where is lactate converted back into glucose?
Liver by gluconeogenesis
What is produced in gluconeogenesis?
NADH
What does gluconeogenesis use?
4 ATP and 2GTP
What does anaerobic glycolysis produce?
2 ATP and NAD+ for glycolysis
How is glycerol generated?
From the hydrolysis of triacylglycerols in adipose tissue (storage form of fat)
How is glycerol transported to the liver for gluconeogenesis?
By the blood from the adipocytes
Adipocytes lack glycerol kinase
What does glycerol kinase do and where does the energy come from?
Adds a phosphate group to glycerol to make glycerol phosphate and uses ATP as the phosphate source and energy source
Kinase = phosphate
How is glycerol phosphate oxidized into dihydroxyacetone phosphate?
Glycerol phosphate dehydrogenase oxidizes glycerol phosphate and reduces NAD+ to NADH and H+
What reactions in gluconeogenesis use the same enzymes as glycolysis?
Step 3-8
Why is an enzyme other than phosphofructokinase 1 needed in gluconeogenesis?
PFK-1 is a committed step in glycolysis and is highly regulated
What does frucose-1,6-bisphosphatase do?
Dephosphorylates Carbon 1 of Fructose 1,6 - bisphosphate to make fructose -6- phosphate
Uses water to create a hydroxyl group in place of a phosphate
Hydrolysis/does not generate ATP
How is this step regulated in gluconeogenesis?
By an allosteric enzyme
Inhibited by AMP (poor energy state)
Activated by high levels of ATP (high energy state)
What does phosphohexose isomerase do?
Converts fructose 6-p to glucose 6-p (furanose to a pyranose)
What is the final step of gluconeogenesis?
Conversion of glucose 6 phosphate to glucose
Why is hexokinase kept in a separate cellular compartment from glucose 6 phosphotase?
To prevent a futile cycle (hexokinase adds a phosphate group to glucose while glucose 6 phosphotase takes off a phosphate group from glucose 6 p
Where is glucose 6P dephosphorylated to free glucose?
In the smooth ER of the liver and kidney cells
NONE IN MUSCLE CELLS
What can export free glucose to the blood?
GLUT 2
Why is gluconeogenesis expensive?
Costs 4 ATP, 2 GTP and 2NADH
Why is gluconeogenesis necessary even though it is so expensive?
To supply glucose to Brain, nervous system, and red blood cells that can use glucose to make ATP
What does gluconeogenesis allow for when glycogen stores are depleted?
Generation of glucose during fasting and starvation, vigorous exercise (cori cycle brings lactate from muscles), can generate glucose from AAs, glycerol, and lactate
How are gluconeogenesis and glycolysis reciprocally regulated?
Regulated so that within a cell one pathway is inactive while the other is active
When will glycolysis predominate over gluconeogenesis?
When glucose is abundant
When will gluconeogenesis be highly active?
When glucose is low
Where are glycolysis and gluconeogenesis reciprocally regulated?
The interconversion of fructose 1,6-bisphosphate and fructose 6 phosphate
Interconversion of PEP and pyruvate
Where does the pentose phosphate pathway occur?
In the cytoplasm
What is the initial substrate for PPP?
Glucose 6P
What are the main products of the PPP?
2 NADPH and ribose 5 phosphate
What is NADPH used for?
It is an electron donor
Reductive biosynthesis of fatty acids and steroids
Repairs oxidative damage
What is Ribose 5 phosphate and what is it used for?
Biosynthetic precursor of nucleotides and is used for DNA and RNA synthesis
Used for synthesis of coenzymes and ATP
What kind of pathways use NADP+ instead of NAD+?
Anabolic (building up) pathways use NADP+ while catabolic pathways use NAD+
What kind of synthesis is NADPH used for?
Fatty acid
Cholesterol
Neurotransmitter
Nucleotide
How is NADPH used for detoxification?
TO neutralize reactive oxygen species
Reduction of glutathione
How does NADP+ differ from NAD+?
It has a phosphorylated ribose
What are the two phases of PPP?`
Oxidative (steps 1-3) that produces NADPH and Ribulose 5 phosphate
Nonoxidative (remaining reactions) Converts sugars into sugar phosphates and is reversible
When would PPP be used?
If increased NADPH is required
If nucleotide pools need to be replenished
If ATP levels are low
What enzyme is used in the regulating step of the oxidative phase of PPP?
Glucose 6 phosphate dehydrogenase
What enzyme in the oxidative phase of PPP is used to release carbon from glucose as CO2?
6Phosphogluconate dehydrogenase
What is ribulose 5 phosphate used for?
DNA/RNA biosynthesis
Where is NADPH needed for fatty acid biosynthesis?
Liver
Lactating mammary glands
Adipose tissue
Where is NADPH needed for the biosynthesis of steroid hormones?
Testes, ovaries, placenta
What does the nonoxidative phase of PPP do?
Regenerates glucose 6 p from ribose 5 p
Where does the nonoxidative phase of PPP occur?
in all cells synthesizing nuclotides
How much ATP is used in the nonoxidative phase of PPP?
None
What can the intermediates of nonoxidative phase of PPP do?
Feed into glycolysis
Make ribose 5 phosphate
When will glucose 6 P be pushed into the PPP?
When NADP+ levels are high
What allosterically activates Glucose 6 phosphate dehydrogenase in PPP?
NADP+
How is PPP down regulated?
When NADPH levels are high NADPH and NADP+ compete for binding with G6PD which causes lower enzyme activity
What is a reactive oxygen species ROS that is a byproduct of aerobic metabolism and from drugs and environmental toxins?
H2O2
What is glutathione reductase dependent upon?
NADPH (it needs to be oxidized in order for Glutathione to be reduces on the cysteine residue
What does glutathione peroxidase do?
Oxidizes glutathione and neutralizes H2O2 into 2 H2O
What happens in G6P dehydrogenase deficiency?
NADPH production is diminished
Glutathione levels are deplete
THis inhibits H2O2 detoxification and results in higher levels of ROS
What does G6P dehydrogenase deficiency lead to?
Oxidative damage to lipids, proteins and DNA
Lysis of RBC (jaundice)
What do monooxygenases do?
Incorporate one atom from O2 into a substrate to create a hydroxyl group
What does cytochrome P450 monooxygenase do in the inner mitochondrial membrane?
Synthesizes steroid hormones in steroidogenic tissues and in bile acid synthesis in liver
What is cytochrome P450 monooxygenase system used for in the smooth ER?
Detoxification
