Metabolism 2 Flashcards
Glycolysis (takes place in the ___)
- Also known as the ____-___ Pathway
- Glucose is an universal fuel for all cells
- __ ___ type is able to generate ___ from glycolysis
- Occurs by ___ and___ of glucose to pyruvate
- Dependent on the ___ of ___ in the blood
- Occurs in the___ and ___ of O2
- Provides ___ ___ (Ex – pyruvate converted to acetyl CoA for fatty acid synthesis)
Glycolysis (takes place in the cytosol)
Also known as the Embden-Meyerhof Pathway
Glucose is an universal fuel for all cells
Every cell type is able to generate ATP from glycolysis
Occurs by oxidation and cleavage of glucose to pyruvate
Dependent on the availability of glucose in the blood
Occurs in the presence and absen ce of O2
Provides biosynthetic precursors (Ex – pyruvate converted to acetyl CoA for fatty acid synthesis)
Main function of the glycolytic pathway
____ ____ ____ ___ ___ –> ____ ____ ____ ____ ___ ____
Pyruvate–> ___: Higher organisms
Pyruvate + O2 –> __ and ___
Pyruvate–>___: Yeast
Main function of the glycolytic pathway
Glucose + 2 ATP + 2 Pi + 4 ADP + 2 NAD+ à 2 pyruvate + 2 ADP + 4 ATP + 2 NADH + 2H+ + 2 H2O
Pyruvateà Lactate: Higher organisms
Pyruvate + O2à CO2 and H2O
PyruvateàEthanol: Yeast
Types of reactions which occur in glycolysis
Phosphoryl Transfer: ____ (Transfer of phosphoryl
group from ___)
Phosphoryl Shift: ____ (Shift of phosphoryl group
from ____ ____ a molecule)
Isomerization: ____ (___ converted to ___
or vice versa)
Dehydration:____ (___of ___)
Aldol Cleavage: ____ (Split of __ bond)
Types of reactions which occur in glycolysis
Phosphoryl Transfer: Kinase (Transfer of phosphoryl
group from ATP)
Phosphoryl Shift: Mutase (Shift of phosphoryl group
from oxygen within a molecule)
Isomerization: Isomerase (Ketose converted to aldose
or vice versa)
Dehydration: Dehydrogenase (Elimination of Water)
Aldol Cleavage: Aldolase (Split of C-C bond)
Stages of glycolysis
The first stage ___ glucose within the cell by ____ (phosphate has – charge) and the eventual conversion to _______
The second stage forms _ ____ from the 6-carbon fructose 1,6-bisphosphate
In the final stage ____ is formed from trioses
Stages of glycolysis
The first stage traps glucose within the cell by phosphorylation (phosphate has – charge) and the eventual conversion to fructose 1,6-bisphosphate
The second stage forms 2 trioses from the 6-carbon fructose 1,6-bisphosphate
In the final stage pyruvate is formed from trioses
Stage I (___ phase): ____ to ____ (Steps 1-3). Use___
Stage II (conversion of ___ to___): ____ to ____ (Steps 4-5)
Stage III (___ phase): ___ to ____ (Steps 6-8). Produce ____ and ___.
Stage I (preparatory phase): Glucose to F16BP (Steps 1-3). Use 2 ATP
Stage II (conversion of hexose to trioses): F16BP to 2 G3P (Steps 4-5)
Stage III (payoff phase): G3P to Pyruvate (Steps 6-8). Produce 4 ATP, 2 NADH
ATP produced by substrate level phosphorylation
Substrate level phosphorylation refers to the ____ of ___ to form ATP independent of ___ ___.
ATP produced by substrate level phosphorylation
Substrate level phosphorylation refers to the phosphorylation of ADP to form ATP independent of electron transport.
Net reaction of the glycolytic pathway
Glucose + 2 Pi + 2 ADP + 2 NAD+ à 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
Net reaction of the glycolytic pathway
Glucose + 2 Pi + 2 ADP + 2 NAD+ à 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
The metabolic fate of pyruvate
- Under aerobic conditions
- Pyruvate–>______
- Enzyme: ___ ____
- Under anaerobic conditions
- Pyruvate–>Ethanol + 2CO2
- Pyruvate +____–> ___ + ____
- Enxzyme: ____ _____
- Pool of NAD/NADH is always ___ in the body.
- We don’t syn extra NADH to compensate them being used
- You need ___ to go thru___
- This regenerates ___ from NADH to continue glycolysi
The metabolic fate of pyruvate
Under aerobic conditions
PyruvateàAcetyl CoA
Enzyme: Pyruvate Dehydrogenase
Under anaerobic conditions
PyruvateàEthanol + 2CO2
Pyruvate + NADHà Lactate + NAD+
Lactate Dehydrogenase
Pool of NAD/NADH is always constant in the body.
We don’t syn extra NADH to compensate them being used
You need NAD to go thru glycolysis.
This regenerates NAD+ from NADH to continue glycolysis
Rate limiting steps in the glycolytic pathway
Main rate limiting step is the irreversible reaction catalyzed by __________
- ____ inhibits PFK-1, while ___ reverses the inhibition (energy charge)
- ____ is an allosteric ____ (Product of CAC)
- _____ _____ PFK-1 activity
- ___ ____ PFK-1 – prevents lactate build up under anaerobic conditions (acidosis
Hexokinase (Called ____ in liver where it has ___ Km, induced by ___,)
- Most tissues it has ___ Km (high affinity) of glucose
- Only when you have super high glucose in blood will liver take it up. Liver wants make sure blood glucose levels stay constant and wants to ensure brain gets glucose
- Inhibited by ________ due to inhibition of PFK-1
Pyruvate kinase
- ___ by _____
- ___ by ___ (energy charge) and ___
- Alanine is aa derived from pyruvate
- ___ by ____ (via ___ __ ___ via ___ and ____)
Rate limiting steps in the glycolytic pathway
Main rate limiting step is the irreversible reaction catalyzed by Phosphofructokinase (PFK-1)
ATP inhibits PFK-1, while AMP reverses the inhibition (energy charge)
Citrate is an allosteric inhibitor (Product of CAC)
Fructose 2,6-bisphosphate stimulates PFK-1 activity
H+ inhibits PFK-1 – prevents lactate build up under anaerobic conditions (acidosis)
Hexokinase (Called Glucokinase in liver where it has high Km, induced by insulin,)
Most tissues it has low Km (high affinity) of glucose
Only when you have super high glucose in blood will liver take it up. Liver wants make sure blood glucose levels stay constant and wants to ensure brain gets glucose
Inhibited by Glucose 6-phosphate due to inhibition of PFK-1
Pyruvate kinase
Activated by Fructose 1,6-bisphosphate
Inhibited by ATP (energy charge) and alanine
Alanine is aa derived from pyruvate
Inhibited by phosphorylation (via protein kinase A via glucagon and epinephrine)
Fructose 2,6-bisphosphate regulates the activity of PFK-1
Fructose 2,6 Bisphosphate occurs only in the ____
____ Phosphofructokinase
Formed from _______ by ___
Converted back to _____ by _________
____enzyme
Side product—Not part of either pathway
Fructose 2,6-bisphosphate regulates the activity of PFK-1
Fructose 2,6 Bisphosphate occurs only in the liver.
Stimulates Phosphofructokinase
Formed from Fructose 6-phosphate by PFK-2
Converted back to Fructose 6-phosphate by Fructose 2,6-bisphosphatase
Bifunctional enzyme
Side product—Not part of either pathway
Formation of fructose 2,6-bisphosphate is controlled by ____
Phosphofructokinase-2 & Fructose 2,6-bisphosphatase (Bifunctional enzyme) reciprocally regulated by____ _____
After meal:
- High blood glucose (___high)
- ____ Phosphofructokinase-2 is ____
- ___ stimulated
Before meal:
- Low blood glucose (____ high)
- _____ Phosphofructokinase-2 —____ (wont produce F26BP)
- ______ stimulated
Formation of fructose 2,6-bisphosphate is controlled by phosphorylation
Phosphofructokinase-2 & Fructose 2,6-bisphosphatase (Bifunctional enzyme) reciprocally regulated by serine phosphorylation
After meal:
High blood glucose (Insulin high)
Dephosphorylated Phosphofructokinase-2 is active
Glycolysis stimulated
Before meal:
Low blood glucose (Glucagon high)
Phosphorylated Phosphofructokinase-2 —Inactive (wont produce F26BP)
Gluconeogenesis stimulated
Regulation in Liver
Goal: Provide glucose for the body
Allow liver to replenish blood glucose
High glucose ⇨ _ F 2,6 BP ⇨ _ Glycolysis
Starvation ⇨_ F 2,6 BP ⇨_Gluconeogenesis
Regulation in Liver
Goal: Provide glucose for the body
Allow liver to replenish blood glucose
High glucose ⇨ ↑ F 2,6 BP ⇨ ↑ Glycolysis
Starvation ⇨↓ F 2,6 BP ⇨↑Gluconeogenesis
Regulation of pyruvate kinase is Allosteric and Covalent
Phosphorylated: Less Active
Dephosphorylated: More active
+ F16BP
- Alanine, ATP
Regulation of pyruvate kinase is Allosteric and Covalent
Summary
The overall function of glycolysis is to convert glucose into 2 molecules of pyruvate.
A net ___ ATP’s are formed by glycolysis
Glycolytic intermediates are used as building blocks for other metabolic pathways
Glycolysis occurs in the cell’s ____
Under aerobic conditions, pyruvate is converted to ____
Regulation of glycolysis reflects ___ ____ and the level of ___ ___ available in the cell
The ____ reaction is the main regulatory point of glycolysis
Summary
The overall function of glycolysis is to convert glucose into 2 molecules of pyruvate.
A net of 2 ATP’s are formed by glycolysis
Glycolytic intermediates are used as building blocks for other metabolic pathways
Glycolysis occurs in the cell’s cytoplasm
Under aerobic conditions, pyruvate is converted to acetyl CoA
Regulation of glycolysis reflects energy charge and the level of metabolic intermediates available in the cell
The phosphofructokinase reaction is the main regulatory point of glycolysis
Citric Acid Cycle (CAC)
Occurs in the ___ of the ____
___ ___ pathway where oxidation of ___ ,___ and ____occurs
Provides reduced coenzymes ___ ____ ___ and ____ ___
Citric Acid Cycle (CAC)
Occurs in the matrix of the mitochondrion
Final common pathway where oxidation of fats, carbohydrates and amino acids occurs
Provides reduced coenzymes NADH, FADH2, GTP and biosynthetic precursors
Number of ATP generated by the CAC
- Pyruvate Dehydrogenase
- _ NADH: _ ATP
- CAC (one cycle)
- _ NADH: ___ ATP
- _ FADH2: __ ATP
- _ GTP: _ ATP
- Subtotal/glucose: __ ATP
- Glycolysis
- _ NADH: _ ATP
- Net: _ (or __) ATP
Number of ATP generated by the CAC
Pyruvate Dehydrogenase
1 NADH: 2.5 ATP
CAC (one cycle)
3 NADH: 7.5 ATP
1 FADH2: 1.5 ATP
1 GTP: 1 ATP
Subtotal/glucose: 25 ATP
Glycolysis
2 NADH: 5 ATP
Net: 30 (or 32) ATP
Interaction of intermediates of the CAC with other pathways
- a-ketoglutarate can be used in the ____ of ____
- Succinyl CoA is used in _____ (___) _____
- Oxaloacetate can be used in the ____ of ____
- When intermediates of CAC are used by other pathways, they must be____
- Known as____ reactions
*
Interaction of intermediates of the CAC with other pathways
a-ketoglutarate can be used in the biosynthesis of amino acids
Succinyl CoA is used in porphyrin (heme) biosynthesis
Oxaloacetate can be used in the biosynthesis of amino acids
When intermediates of CAC are used by other pathways, they must be replenished
Known as anaplerotic reactions
Pyruvate dehydrogenase complex
- ___ ____ component
- Cofactor: ___ ____
- Rxn: ___ ____ of____
- ____ ____ component
- Cofactor:___
- Rxn:___ of ____ ___ to ___
- ____ _____ component
- Cofactor: ___
- Rxn: ____ ____ ____
Pyruvate dehydrogenase complex
Pyruvate dehydrogenase component
Cofactor: Thiamine Pyrophosphate
Rxn: Oxidative Decarboxylation of Pyruvate
Dihydrolipoyl transacetylase component
Cofactor: Lipoamide
Rxn: Transfer of acetyl group to CoA
Dihidrolipoyl dehydrogenase component
Cofactor: FAD
Rxn: Regenerate oxidized lipoamide
Rate Limiting Steps
- ____–>_____
- Enzyme:____ _____
- Cofactor: ____ ____, ____ , ____
- ____–>_____
- Enzyme: _____
- Cofactor: ___
- ____–>_____
- Enzyme: ____ _____
- ____–>____
- Enzyme: ____ ____
- Cofactor: ___ ___, ____ , ___
Rate Limiting Steps
Pyruvateà Acetyl CoA
Enzyme: Pyruvate Dehydrogenase
Cofactor: Thiamine Pyrophosphate, Lipoamide, FAD
CitrateàIsocitrate
Enzyme: Aconitase
Cofactor: Fe-S
Isocitrateà Alpha Ketoglutarate
Enzyme: Isocitrate Dehydrogenase
Alpha KetoglutarateàSuccinyl CoA
Enzyme: AKG Dehydrogenase
Cofactor: Lipoic Acid, FAD, TPP
Rate limiting steps in the citric acid cycle
- Citrate synthase
- Inhibited by ___ and ____
- Isocitrate dehydrogenase
- Inhibited by___ and ___, while activated by ___ (energy charge)
- a-ketoglutarate dehydrogenase
- Inhibited by ___ and ____
- Pyruvate dehydrogenase
- ___ by ___ ___ ___ inactivates enzyme
- ____ and ____ stimulate kinase activity
- Inhibited by ___ and ___
- Dephosphorylation by _____
- Stimulated by ____
- Product inhibition by ____ and___
- ___ by ___ ___ ___ inactivates enzyme
Rate limiting steps in the citric acid cycle
Citrate synthase
Inhibited by citrate and ATP
Isocitrate dehydrogenase
Inhibited by NADH and ATP, while activated by ADP (energy charge)
a-ketoglutarate dehydrogenase
Inhibited by NADH and succinyl CoA
Pyruvate dehydrogenasePhosphorylation by Pyruvate dehydrogenase kinase inactivates enzyme
Acetyl CoA and NADH stimulate kinase activity
Inhibited by pyruvate and ADP
Dephosphorylation by Phosphatase
Stimulated by Ca2+
Product inhibition by acetyl CoA and NADH
Regulation of pyruvate dehydrogenase
Inhibited by products of reaction; ____ and ____
Also inhibited by ___
Interact allosterically with ____ and also Affect ____
Regulation of pyruvate dehydrogenase
Inhibited by products of reaction; Acetyl CoA; NADH
Also inhibited by ATP
Interact allosterically with PDH and also effect kinase
Control of Pyruvate Dehydrogenase
_____ Phosphorylation
___ ____ component ___ phosphorylated by specific kinase
Reversed by specific ___
Conditions which favor ____ energy charge promote phosphorylation and ____ of complex
Control of Pyruvate Dehydrogenase
Reversible Phosphorylation
Pyruvate dehydrogenase component E1 phosphorylated by specific kinase
Reversed by specific phosphatase
Conditions which favor increased energy charge promote phosphorylation and inactivation of complex
Summary
Pyruvate is converted to __ __ by the ___ __ __
The pyruvate dehydrogenase complex contains s___ ___ ___ and ___ and is the key step regulating the flow of C-2 units into the citric acid cycle
_____ condenses with ____ to form ___ as the first step of the actual cycle
One round of the citric acid cycle results in the formation of _ GTP, _NADH, _ FADH2, and _ ___
Anaplerotic reactions replenish cycle intermediates drawn off for the biosynthesis of other biomolecules such as amino acids
Summary
Pyruvate is converted to acetyl CoA by the pyruvate dehydrogenase complex
The pyruvate dehydrogenase complex contains several enzyme activities and cofactors and is the key step regulating the flow of C-2 units into the citric acid cycle
Acetyl CoA condenses with oxaloacetate to form citrate as the first step of the actual cycle
One round of the citric acid cycle results in the formation of 1 GTP, 3NADH, 1 FADH2, and 2 CO2
Anaplerotic reactions replenish cycle intermediates drawn off for the biosynthesis of other biomolecules such as amino acids
Purpose of the Pentose Phosphate Pathway
Also known as the ___ ___, ___ _____ pathway, or the _____ ____pathway
Involved in the generation of
- ____ for ___ _____ reactions such as__ ___ synthesis
- ___-__-___ for ___, ___ and ___ synthesis
- __ ___ intermediates for ___ and ____ pathways.
*
Purpose of the Pentose Phosphate Pathway
Also known as the pentose shunt, hexose monophosphate pathway, or the phosphogluconate oxidation pathway
Involved in the generation of
NADPH for reductive biosynthesis reactions such as fatty acid synthesis
Ribose-5-phosphate for DNA, RNA and nucleotide synthesis
Sugar phosphate intermediates for glycolytic and gluconeogenesis pathways.
PPP consists of two branches
____branch
___-__ -____ is converted to ___-__-____ with the formation of _ molecules of ____
____ ____ branch
____ the __-carbon sugar phosphates formed by the oxidative branch into ____ that can be used by ___ or ____
PPP consists of two branches
Oxidative branch
Glucose 6-phosphate is converted to ribulose 5-phosphate with the formation of 2 molecules of NADPH
Non-oxidative branch
Rearranges the 5-carbon sugar phosphates formed by the oxidative branch into intermediates that can be used by glycolysis or gluconeogenesis
Oxidative branch of PPP
Formation of____-_-____ from ___-_-____
Catalyzed by the enzyme_____________
Ribulose 5 P–> ____-__-___
Catalyzed by the enzyme __________
Oxidative branch of PPP
Formation of ribulose-5-phosphate from Glucose 6 Phosphate
Catalyzed by the enzyme glucose-6-phosphate dehydrogenase
Ribulose 5 P-à ribose-5-phosphate
Catalyzed by the enzyme phosphopentose isomerase
Non-oxidative branch
Excess_______ is converted to ___ ____ (_______ and ______)
Ribose 5 P: Go thru series of rxns. (Change from___ to ___ to ____)
Catalyzed by _____ and _____
Non-oxidative branch
Excess ribose-5-phosphate is converted to glycolytic intermediates glyceraldehyde-3-phosphate and fructose-6-phosphate
Ribose 5 P: Go thru series of rxns. (Change from ketose to aldose to ketose)
Catalyzed by transketolases and transaldolases
Regulation and tissue localization of PPP
Controlled by concentration of ____
____ NADP+ then you stimulate the pathway (want to make more NADPH)
Highest activity in the ___ ___ and lowest in the ___
Regulation and tissue localization of PPP
Controlled by concentration of NADP+
High NADP+ then you stimulate the pathway (want to make more NADPH)
Highest activity in the adipose tissue and lowest in the muscle
Abnormality in transaldolase leads to ____ of the ____
If you have defect in transaldolase, you get a build up of the____
Will convert back to _____ and that will get converted to ___
Ribitol is 5C alcohol. Has several ___ ___; ____!
Abnormality in transaldolase leads to cirrhosis of the liver
If you have defect in transaldolase, you get a build up of the produces
Will convert back to Ribose 5P and that will get converted to ribitol
Ribitol is 5C alcohol. Has several OH groups, toxic!
Disease caused by abnormality in glucose 6-phosphate dehydrogenase
___ ____ due to ___ or___ ____ and by oxidation of ____ leads to____of red blood cells.
Inability to reduce _____ due to the absence of _____________
Glutathione is involved in the ____ of______
Leads to____ of ____ and ____ to ___ ____ causing ___ of RBCs.
Defect in pathway: Can’t produce NADPH
Glutathione Reducatase: creates _____ from ____ form. That rxn requires ____
Reduced Glutathione will be used to ____ the H2O2 to H2O
If don’t have NADPH, oxidative stress will build up
Disease caused by abnormality in glucose 6-phosphate dehydrogenase
Oxidative stress due to infection or drug interactions and by oxidation of hemoglobin leads to hemolysis of red blood cells.
Inability to reduce glutathione due to the absence of glucose 6-phosphate dehydrogenase
Glutathione is involved in the detoxification of Reactive oxygen species (ROS)
Leads to crosslinking of hemoglobin and damage to cell membrane causing lysis of RBCs.
Defect in pathway: Can’t produce NADPH
Glutathione Reducatase: creates glutathione from oxidized form. That rxn requires NADPH
Reduced Glutathione will be used to neutralize the H2O2 to H2O
If don’t have NADPH, oxidative stress will build up
Summary
The PPP produces
- ____ for reductive biosynthetic reactions
- _______ for the synthesis of RNA, DNA, and nucleotide Coenzymes
- ___ ____ for glycolysis
The PPP is most active in adipose tissue and is controlled by the concentration of NADP+
Summary
The PPP produces
NADPH for reductive biosynthetic reactions
Ribose 5-phosphate for the synthesis of RNA, DNA, and nucleotide Coenzymes
Metabolic intermediates for glycolysis
The PPP is most active in adipose tissue and is controlled by the concentration of NADP+
Gluconeogenesis
Synthesis of ____ from ___-____ precursors such ___,____,____
Major function is to provide glucose to the___ and ____
____ a direct reversal of glycolysis
∆Gº’ would be ___ kcal/mol
Some of glycolysis enzymes are used
3 reactions “___”
Glucose is primary fuel source for ___,___
___ and ___ provide glucose
Gluconeogenesis
Synthesis of glucose from non-carbohydrate precursors such alanine, lactate and glycerol
Major function is to provide glucose to the brain and muscles
NOT a direct reversal of glycolysis
∆Gº’ would be +20 kcal/mol
Some of glycolysis enzymes are used
3 reactions “bypassed”
Glucose is primary fuel source for brain, muscle
Liver & kidney provide glucose
Gluconeogenesis takes place in the __ and ___
___–>____ takes place in liver only
Gluconeogenesis takes place in the liver and kidney
G6PàGlucose takes place in liver only
Non- Reversal Steps
(Lactateà)___–>___
(Some aaà)____–>___
___–>___
___–>___
Non- Reversal Steps
(Lactateà)PyruvateàOxaloacetate
(Some aaà)OxaloacetateàPEP
F16BPàF6P
G6PàGlucose
Gluconeogenesis is not a reversal of glycolysis
The bypass reactions make the synthesis of glucose ____ ____
Gluconeogenesis is not a reversal of glycolysis
The bypass reactions make the synthesis of glucose thermodynamically feasible
Oxaloacetic Acid
____ intermediate for ____ AND ____ intermediate for _____
___level determines the fate of Oxaloacetate
High [___] ð ________
Low [___] ð _____
Oxaloacetic Acid
Stoichiometric intermediate for gluconeogenesis AND catalytic intermediate for Citric acid cycle
ATP level determines the fate of Oxaloacetate
High [ATP] ð Gluconeogenesis
Low [ATP] ð Citric acid cycle
1st “Bypass reaction”: Reverse ___ → ____
_ reactions are required
- ___ + ___ + ___ + ___ → ____+____+____+____
- Enzyme: _____ _____
- ____ + ___ ⇌ _____ + ___ + ____
- Enzyme: ___ ______
- Pyruvate carboxylase—_____ enzyme containing____
- ____ ___ allosteric activator of pyruvate carboxylase
- Must bind for ____ of ___ to occur
- ____ [___ ___] signals need for OAA
*
- ____ ___ allosteric activator of pyruvate carboxylase
1st “Bypass reaction”: Reverse PEP → pyruvate
2 reactions are required
Pyruvate + CO2 + ATP + H2O → oxaloacetate + ADP + Pi + 2 H+
Enzyme: Pyruvate carboxylase
Oxaloacetate + GTP ⇌ phosphoenolpyruvate + GDP + CO2
Enzyme: PEP carboxykinase
Pyruvate carboxylase—mitochondrial enzyme containing biotinAcetyl CoA allosteric activator of pyruvate carboxylase
Must bind for carboxylation of biotin to occur
High [Acetyl CoA] signals need for OAA
Role of biotin in pyruvate carboxylase
Biotin basically ____ ____
That will react with ___ to give you ____
Need ___ for rxn to be ____
Role of biotin in pyruvate carboxylase
Biotin basically activates CO2
That will react with pyruvate to give you oxaloacetate
Need biotin for rxn to be favorable
Shuttling of oxaloacetate to the cytosol
All enzymes of gluconeogenesis are found in the ____, expect ___ ____ (found in ____)
Oxaloacetate is converted to ___ by ___-linked ___ ____
Once in the cytosol
- ___ is ____ to _____ by __-linked ___ _____
- Oxaloacetate is further _____ and ____ by ____ ____ to phosphoenolpyruvate
Shuttling of oxaloacetate to the cytosol
All enzymes of gluconeogenesis are found in the cytosol, expect pyruvate carboxylase (found in mitochondria)
Oxaloacetate is converted to malate by NADH-linked malate dehydrogenase
Once in the cytosol
Malate is reoxidized to oxaloacetate by NAD-linked malate dehydrogenase
Oxaloacetate is further decarboxylated and phosphorylated by phosphoenolpyruvate carboxykinase to phosphoenolpyruvate
2nd & 3rd “Bypass reactions” of Gluconeogenesis
- ______ + ___ –> _______ + ____
- Enzyme:____________
- _____ + ___–>____+___
- Enzyme: __________
- ___ ___
- In ___ of ___
*
2nd & 3rd “Bypass reactions” of Gluconeogenesis
Fructose 1, 6-bisphosphate + H2O àfructose 6-phosphate + Pi
Enzyme: Fructose 1,6-bisphosphatase
Glucose 6-phosphate + H2Oàglucose + Pi
Enzyme: Glucose 6-phosphatase
Liver ONLY
In lumen of ER
Liver
In lumen of ER
Rate limiting steps in gluconeogenesis
- Pyruvate carboxylase
- Activated by ____ and inhibited by ___
- Phosphoenolpyruvate carboxykinase
- Inhibited by ___
- Induced (level of transcription) by___ and ___ and repressed by ____
- Glucose 6-phosphatase
- Induced during____
*
- Induced during____
Rate limiting steps in gluconeogenesis
Pyruvate carboxylase
Activated by Acetyl CoA and inhibited by ADP
Phosphoenolpyruvate carboxykinase
Inhibited by ADP
Induced (level of transcription) by glucagon and epinephrine and repressed by insulin
Glucose 6-phosphatase
Induced during fasting
Lactate as precursor for gluconeogenesis – ___ cycle
Lactate is produced in ___ ___ ___ because
- ___ and ___ accumulates
- ____ is required for glycolysis to continue
- Lactate is transported to the ___ via___ and ___ to ___
Lactate produced in muscle cells via ___ ___
Lactate produced from ___ and ___
NAD/NADH is constant
Need to regenerate NAD for glycolysis to occur
BUT Lactate can be___ (you start to cramp) so it needs to transported to liver
Regenerate Pyruvate
Lactate as precursor for gluconeogenesis – Cori cycle
Lactate is produced in active skeletal muscles because
Pyruvate and NADH accumulates
NAD+ is required for glycolysis to continue
Lactate is transported to the liver via blood and reoxidized to pyruvate
Lactate produced in muscle cells via anaerobic respiration.
Lactate produced from NADH and pyruvate
NAD/NADH is constant
Need to regenerate NAD for glycolysis to occur
BUT Lactate can be toxic (you start to cramp) so it needs to transported to liver
Regenerate Pyruvate
Role of lactate dehydrogenase
In ___ ___ ____
- Converts ___ and ___ to ___ and ___ (___NADH/ NAD+ ratio)
- Lactate ___ to the ____ or used as ___ by ___ ___
In the liver
- Converts ___ to ___ (___ NADH/ NAD+ ratio)
- ___ converted to ____
Role of lactate dehydrogenase
In active skeletal muscles
Converts pyruvate and NADH to lactate and NAD+ (low NADH/ NAD+ ratio)
Lactate transported to the liver or used as fuel by resting muscles.
In the liver
Converts lactate to pyruvate (high NADH/ NAD+ ratio)
Pyruvate converted to glucose
Summary
Glucose production from non carbohydrate precursors ___ ,___ and ____
The pathway utilizes reverse reactions of glycolysis as well as bypass reaction unique to the pathway
Gluconeogenesis and_____ (preferred) are carefully regulated pathways that control ____ blood glucose levels during fed and fasting conditions.
Summary
Glucose production from non carbohydrate precursors lactate, glycerol and amino acids
The pathway utilizes reverse reactions of glycolysis as well as bypass reaction unique to the pathway
Gluconeogenesis and glycogenolysis (preferred) are carefully regulated pathways that control constant blood glucose levels during fed and fasting conditions.
