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Flashcards in Metabolism 2 Deck (44)
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1

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)

 

2

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

 

3

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)

 

4

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

 

5

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

6

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.

 

7

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

 

8

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

 

9

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)

 

10

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

 

11

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

 

12

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

 

 

13

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

14

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

 

15

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

 

16

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

 

17

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

 

18

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

 

19

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

20

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___

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

21

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

 

22

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

 

23

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

 

24

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.

 

25

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

 

26

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

 

27

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

 

28

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

 

29

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!

30

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