Metabolism 2 Flashcards
(44 cards)
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.
