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Flashcards in Metabolism 1 Deck (36):
1

Metabolism is

A highly integrated network of chemical reactions from which___ and ____ ____ are derived.

___ and____  pathways.

Essentially the same in ___ ___ and ____

Metabolism is

A highly integrated network of chemical reactions from which energy and biological precursors are derived.

Coupled and interconnected pathways.

Essentially the same in bacteria, plants, and animals.

 

2

Catabolism is the ____ pathways to salvage ___ and ___ from ____ such as nucleotides, proteins, lipids and polysaccharides.  The process ____ energy. (___gonic reaction)

 

Anabolism is the____ of _____ such as nucleotides, proteins, lipids and polysaccharides from ___ ____ molecules.  This process ____energy. (___gonic reaction)

 

Catabolism is the degradation pathways to salvage components and energy from biomolecules such as nucleotides, proteins, lipids and polysaccharides.  The process generates energy. (Exergonic reaction)

 

Anabolism is the biosynthesis of biomolecules such as nucleotides, proteins, lipids and polysaccharides from simple precursor molecules.  This process requires energy. (Endergonic reaction)

 

3

Four Principles of Metabolic Pathways

Metabolic pathways are_____

Every metabolic pathway has a ___ ____

Other reactions are ___ ____

All metabolic pathways are ____

Metabolic pathways in eukaryotes occur in specific ___ ____

 

Four Principles of Metabolic Pathways

Metabolic pathways are irreversible.

Every metabolic pathway has a committed step.

Other reactions are near equilibrium

All metabolic pathways are regulated.

Metabolic pathways in eukaryotes occur in specific cellular locations.

 

4

Bioenergetic Concepts

Standard biological free energy change DG°’

Free energy change under a ____ set of conditions

pH = ___ for biological reactions

Directly related to _____of ___ and ____

 

Bioenergetic Concepts

Standard biological free energy change DG°’

Free energy change under a standard set of conditions

pH = 7.0 for biological reactions

Directly related to concentration of reactants & products

 

5

Adenosine Triphosphate—ATP

___ high energy bonds (______ bonds)

Currency of free energy for the cell

DG° =  ____ kcal/mol Hydolyze ATP and you release 7.3 kcal/mol

 

Adenosine Triphosphate—ATP

2 high energy bonds (phosphoanhydride bonds)

Currency of free energy for the cell

DG° =  -7.3 kcal/mol Hydolyze ATP and you release 7.3 kcal/mol

 

6

“High energy bonds” is a misleading term

DGo for phosphoryl transfer potential for ATP:

Difference in free energies between the reactants and products due to

  • ___ ___
    • Electron Cloud can move around
    • In _____ (part of ATP) you have less resonance structures
    • Single phosphate group (______) has more resonance structuresà more stable
  • ___ ___
    • Phosphate groups have high amount of – charges
    • These – charges will_____ each other so molecule is ___
    • Prefers to be in less negative state than a more negative state. It likes to be cleaved.  In that process, E is expelled
  • ____ due to ____
    • Phosphate groups are highly ___ compared to ____ form
  • These 3 factors contribute to the -7.3 kcal/mol

“High energy bonds” is a misleading term

DGo for phosphoryl transfer potential for ATP:

Difference in free energies between the reactants and products due to

Resonance stabilization

Electron Cloud can move around

In pyrophosphate (part of ATP) you have less resonance structures

Single phosphate group (orthophosphate) has more resonance structuresà more stable

Electrostatic repulsion

Phosphate groups have high amount of – charges

These – charges will repel each other so molecule is unstable

Prefers to be in less negative state than a more negative state. It likes to be cleaved.  In that process, E is expelled

Stabilization due to solvation

Phosphate groups are highly soluble compared to pyrophosphate form

These 3 factors contribute to the -7.3 kcal/mol

7

Central role of ATP

Hydrolysis of ATP produces ___ ____ that is ____ to a molecule involved in an ____ process (It is activated)

Phosphorylation is the process of ATP _____ _____to a molecule

Results in a ____ ____that can complete the intended reaction

Phosphate is ____ when second substrate binds

 

Central role of ATP

Hydrolysis of ATP produces inorganic phosphate that is attached to a molecule involved in an endergonic process (It is activated)

Phosphorylation is the process of ATP transferring phosphate to a molecule

Results in a phosphorylated intermediate that can complete the intended reaction

Phosphate is released when second substrate binds

 

8

Energy Charge

Measure of relative amounts of ___ ___ ____ in cell

Much of metabolism controlled by energy charge

If all ATP: energy charge = __

If all AMP: energy charge = __

Most cells: energy charge = __-__

Catabolic reactions are favored when the energy charge is __, while anabolic reactions are favored when the energy charge is ___

 

Energy Charge

Measure of relative amounts of ATP, ADP, AMP in cell

Much of metabolism controlled by energy charge

If all ATP: energy charge = 1.0

If all AMP: energy charge = 0

Most cells: energy charge = 0.8-0.95

Catabolic reactions are favored when the energy charge is low, while anabolic reactions are favored when the energy charge is high

 

9

Summary

Metabolism is an ___ and ____ network of reactions from which energy and biological precursors are derived.

Near equilibrium reactions are freely ___, where as reactions that function far from equilibrium server as ___ points and make metabolic pathways ___

Exergonic reactions are coupled to endergonic reactions to make them more favorable.

The ___ ___ of a cell determines the fate of catabolic and anabolic reactions.

 

 

Summary

Metabolism is an integrated and interconnected network of reactions from which energy and biological precursors are derived.

Near equilibrium reactions are freely reversible, where as reactions that function far from equilibrium server as regulatory points and make metabolic pathways irreversible.

Exergonic reactions are coupled to endergonic reactions to make them more favorable.

The energy charge of a cell determines the fate of catabolic and anabolic reactions.

 

 

10

Pathways directly involved in ATP synthesis

_______
______
_______

 

Pathways directly involved in ATP synthesis

Oxidative phosphorylation

Glycolysis

Citric acid cycle

 

11

The Mitochondrion

Site of ___ ____

____ membrane

Most of chemistry takes place in ___ ___

Folded into___

Contains proteins of___

All dependent on ___ ___ ___        

High [H+] in ____

Low [H+] in ___

The Mitochondrion

Site of oxidative phosphorylation

Double membrane

Most of chemistry takes place in inner membrane

Folded into cristae

Contains proteins of ETC   

All dependent on proton motive force           

High [H+] in intermembrane space

Low [H+] in matrix

12

Components of the respiratory chain

  • 4 Enzyme complexes (____ in the membrane-->____ protein))
    • I: ____-_ ______ (I) (____ _____ complex)
    • II: ____-_ _____ (II) (____ _____)
    • III: ___ ____ (III) (____ _-_complex)
    • IV: ____ ______ (IV)
    • Only complexes _ _ _ pump protons
  • 2 ___ carriers
    • _ (__________)
    • ____ _

Components of the respiratory chain

4 Enzyme complexes (Fixed in the membraneàtransmembrane protein))

NADH-Q Reductase (I) (NADH dehydrogenase complex)

Succinate-Q Reductase (II) (Succinate dehydrogenase)

Cytochrome Reductase (III) (Cytochrome b-c complex)

Cytochrome Oxidase (IV)

Only complexes I, III, IV pump protons

2 Mobile carriers

Q (Ubiquinone)

Cytochrome c

 

13

Electron carriers involved in oxidative phosphorylation

_____________
______________

*Connect other metabolic pathways to oxidative phosphorylation

 

Electron carriers involved in oxidative phosphorylation

NAD++ 2H++2e-→ NADH+H+

FAD+ 2H++2e-→ FADH2

*Connect other metabolic pathways to oxidative phosphorylation

 

14

Sources of Reduced Coenzymes

Breakdown of ___ ___ and ___

____

Sources of Reduced Coenzymes

Breakdown of

Carbs

Fats

Proteins

CAC

15

Oxidative Phosphorylation

___ ___ and ___ ____ are separate processes that are ____

Two parts to oxidative phosphorylation

Tramsfer of electrons

Synthesis of ATP

à If one shuts down, so will the other. They __ __ __ coupled

 

Oxidative Phosphorylation

Electron transport and ATP synthesis are separate processes that are coupled.

Two parts to oxidative phosphorylation

Tramsfer of electrons

Synthesis of ATP

à If one shuts down, so will the other. They have to be coupled

 

16

Flow of electrons through the chain

NADH will transfer electrons to _______

Electrons move thru _____-->_____-> _____-->_____

Cytochrome oxidase will transfer the electrons to __ forming water.

In order for electrons to move down this way

The electric potentials should become more positive

Electrons are negatively charged and drawn twd more positive potential

If you look carefully, it drops in the middle

_________ drives that electron

The Gibbs Free Energy should become more negative

Used to __ ___ from __ to the __

 

 

Flow of electrons through the chain

NADH will transfer electrons to NADH dehydrogenase

Electrons move thru Ubiquinoneàb-c complexà cytochrome C à cytochrome oxidase

Cytochrome oxidase will transfer the electrons to O2 forming water.

In order for electrons to move down this wayThe electric potentials should become more positive

Electrons are negatively charged and drawn twd more positive potential

If you look carefully, it drops in the middle

High Gibbs free Energy drives that electron

The Gibbs Free Energy should become more negative

Used to pump protons from matrix to the intermembrane space

 

 

17

Electron transfer and proton flow

Pump Protons from ___ to ____

Build a proton gradient

High [H+] in _______--> ____ Gradient

High amount of __ ____ on one side compared to other-->_______

Total: _____ gradient

 

 

 

Electron transfer and proton flow

Pump Protons from MatrixàIntermembrane Space

Build a proton gradient

High [H+] in Intermembrane Spaceà Concentration Gradient

High amount of + charge on one side compared to otheràelectrical gradient

Total: Electrochemical gradient

 

 

 

18

Other complexes transfer electrons to ___ without ___ ___

___ ____

  • ___ transfers its electrons thru here

___ __ ___ ______ (____)

 

Other complexes transfer electrons to CoQ without translocating protons

Succinate dehydrogenase

FAD transfers its electrons thru here

Glycerol 3-phosphate dehydrogenase (shuttle)

 

19

Specific Inhibitors Block at Specific Sites

___ ___ Blocks I

____ Blocks 3

____ Blocks 4

They used inhibitors to determine ___ of the ____

 

 

 

 

 

 

Specific Inhibitors Block at Specific Sites

Amytal rotenoneà Blocks I

Antimycin Aà Blocks 3

CN- COà Blocks 4

They used inhibitors to determine fcn of the complexes

 

 

 

 

 

 

20

Proton Motive Force (gradient) can drive a variety of processes

 

Proton Motive Force (gradient) can drive a variety of processes

ATP synthesis

Heat production

NADPH synthesis

Flagellar Rotation in Bacteria

Active Transport

Electron potential

21

Chemiosmotic Hypothesis

Proposed by Peter Mitchell

___ ___ ___ drives synthesis of ATP

Evidence includes artificial ___ ___ and ____ experiments

He made a ___ vesicle and incorporated bacteriorhodopsin (a protein that responds to light). 

Flash light on it and it actively transports___ from the ___ into the__. Create a gradient.

He also incorporated an ___

When he added ADP and Pi he was able to create ___

Chemiosmotic Hypothesis

Proposed by Peter Mitchell

Proton motive force drives synthesis of ATP

Evidence includes artificial pH gradients and reconstitution experiments

He made a lipid vesicle and incorporated bacteriorhodopsin (a protein that responds to light). 

Flash light on it and it actively transports protons from the media into the vesicle. Create a gradient.

He also incorporated an ATPase

When he added ADP and Pi he was able to create ATP.

22

ATP Synthase (ATPase)

___ enzyme

  • __ Subunit
    • Contains____ site for ATP synthesis
    • Spherical ___
    • 5 different subunits (a-e)
  • __ Subunit
    • Contains ___ ____
    • Transmembrane
    • 4 subunits
  • ___ ____
    • Regulates __ __ & __ __
    • ___ between F1 & F0
  • ____ ____ ____ ____ (OSCP)

Located in ___ ___ ____

Active site facing ____

____ catalyzes ATP ↔ ADP + Pi

Membrane sector forms __ ____

___ ____ regulates H+ transfer

 

ATP Synthase (ATPase)

Multisubunit enzyme

F1 Subunit

Contains catalytic site for ATP synthesis

Spherical headpiece

5 different subunits (a-e)

F0 Subunit

Contains proton channel

Transmembrane

4 subunits

F1 Inhibitor

Regulates proton flow & ATP synthesis

Stalk between F1 & F0

Oligomycin-sensitivity-conferring protein (OSCP)

Located in inner mitochondrial Membrane

Active site facing matrix

Head catalyzes ATP ↔ ADP + Pi

Membrane sector forms H+ pore

Connecting region regulates H+ transfer

 

23

Binding Change Mechanism for ATP Synthase

Mechanism proposed by Paul Boyer & John Walker

__ catalytic sites cycle through _ conformational states

As substrate binds, it takes 3 conformational states

___ ____ drives interconversion of forms of binding sites in enzyme allowing synthesis and release of __
 

Different conformation at 3 catalytic sites

___: allows ADP and Pi to enter

___: allows ADP + Pi to interact

___ produces ATP

Conformation changes due to___ ____

Requires influx of ____ protons to get one ATP

 

 

Binding Change Mechanism for ATP Synthase

Mechanism proposed by Paul Boyer & John Walker

3 catalytic sites cycle through 3 conformational states

As substrate binds, it takes 3 conformational states

Proton gradient drives interconversion of forms of binding sites in enzyme allowing synthesis and release of ATP
 

Different conformation at 3 catalytic sites

Open: allows ADP and Pi to enter

Loose: allows ADP + Pi to interact

Tight: produces ATP

Conformation changes due to proton influx

Requires influx of three protons to get one ATP

 

 

24

Yield of ATP produced during oxidative phosphorylation

NADH à  O2               __ ATP

FADH2 à O2               __ ATP

For each Glucose    ____ ATP

Efficiency of Ox/Phos compared to “burning” glucose = ___%

Ox/Phos more efficient by 32%

 

Yield of ATP produced during oxidative phosphorylation

NADH à  O2               2.5 ATP

FADH2 à O2               1.5 ATP

For each Glucose      30 (32) ATP

Efficiency of Ox/Phos compared to “burning” glucose = 32% àOx/Phos more efficient by 32%

 

25

Respiratory Control

Electrons are transferred to O2 only if________________

Acceptor Control:  ___must be available for oxidative phosphorylation to proceed

Availability of substrates – ___ ___and ____

 

Respiratory Control

Electrons are transferred to O2 only if ADP is phosphorylated to ATP

Acceptor Control:  ADP must be available for oxidative phosphorylation to proceed

Availability of substrates – NADH, phosphate and O2

 

26

Remember that glycolysis takes place in the cytoplasm,

Aerobic oxidation of cytosolic NADH

NADH CANNOT___ ___ ____

We have shuttles

 

_______ shuttle

__directional

Mostly in ___ ___

First identified in ___ ___ ___

 

___ ____ shuttle

__directional

Mostly in ___ and ___

 

 

Remember that glycolysis takes place in the cytoplasm,

Aerobic oxidation of cytosolic NADH

NADH CANNOT cross mitochondrial membranes

We have shuttles

Glycerol 3-phosphate shuttle

Unidirectional

Mostly in skeletal muscle

First identified in Insect flight muscle

Malate-Aspartate shuttle

Bidirectional

Mostly in liver and heart

 

 

27

Glycerol 3-phosphate Shuttle (___ energy)

NADH from glycolysis will reduce __ to __
G3P can freely move thru outer membrane into intermembrane space.

IMS space has glycerol 3 phosphate dehydrogenase

            It has __ that will be reduced to ___

and that will enter ETC

Glycerol 3-phosphate Shuttle (“Costs” energy)

NADH from glycolysis will reduce DHA to G3P.
G3P can freely move thru outer membrane into intermembrane space.

IMS space has glycerol 3 phosphate dehydrogenase

            It has FAD that will be reduced to FADH2

and that will enter ETC

28

Malate-Aspartate Shuttle (_ energy cost)

Takes __ and converts it to ___

___--> ___

Malate ___ ____ equivalents into mitochondria

Malate ___ to oxaloacetate, _____ ____ to ____

 

Malate-Aspartate Shuttle (No energy cost)

Takes Malate and converts it to Aspartate.

Oxaloacetateà Malate

Malate carries reducing equivalents into mitochondria

Malate oxidized to oxaloacetate, NAD reduced to NADH

 

29

Transport across inner & outer mitochondrial membranes

  • Inner membrane
    • ____ number of molecules can cross membrane
      • This is because otherwise you can’t establish____ ____
    • ___ _____ gradient drives transport
    • Specific____
      • For the molecules that must move across like ___ and___
  • Outer membrane has larger __ ____ ____(_____=____ ____ ___ ___)

Transport across inner & outer mitochondrial membranes

Inner membraneLimited number of molecules can cross membrane

This is because otherwise you can’t establish electrochemical gradient

Electrical potential gradient drives transport

Specific translocases

For the molecules that must move across like ADP and Pi

Outer membrane has larger less specific pores (VDAC=voltage-dependent anion channels)

 

30

Transport of ATP, ADP and Pi across the inner membrane

  • ATP ____ to move ATP from ___ to ____

 

Inhibitors

______: Blocks ATP Translocase

_____: Bloccks ATP Synthase proton channel

 

 

 

 

Transport of ATP, ADP and Pi across the inner membrane

ATP translocases to move ATP from mitochondrion to cytoplasm

 

Inhibitors

Atractyloside: Blocks ATP Translocase

Oligomycin: Bloccks ATP Synthase proton channel

 

 

 

 

31

Uncouplers of Oxidative Phosphorylation

Breakdown ___ ____ from ___ ____

Make the ___ ___ more ____

Uncouplers are __ ____ molecules which can ___ the inner mitochondrial membrane

Stimulate the ___ of substrates in the ___ of ____ ____

___ the ___ ____by ___ ____ across the inner membrane

Energy release during electron transport is generated as ___

 

Uncouplers of Oxidative Phosphorylation

Breakdown Electron Transport from ATP synthesis

Make the inner membrane more permeable

Uncouplers are lipid soluble molecules which can cross the inner mitochondrial membrane

Stimulate the oxidation of substrates in the absence of ATP synthesis

Disrupt the proton gradient by transporting protons across the inner membrane

Energy release during electron transport is generated as heat

 

32

Uncoupling of oxidative phosphorylation generates heat

  • Maintain __ ___
    • Who? ___ ,____ and ____
  • ___ adipose tissue which abundant in ____
  • Uncoupling protein (UCP); _____
    • Channel-_____ membrane to ____
    • Regulated by __ __ (______)
  • Babies and hibernating animals have brown fat.
  • The mitochondria have protein called thermogenin which is activated when its cold thru sym NS. This allow thermogenin to be incorporated into inner membrane. It has a channel and it disrupts the proton gradient. Now you synthesize heat instead of ATP. 

Uncoupling of oxidative phosphorylation generates heat

Maintain body temperature

Hibernating animals, newborns, animals adapted to cold

Brown adipose tissue which abundant in mitochondria

Uncoupling protein (UCP); thermogenin

Channel-permeabilizes membrane to protons

Regulated by fatty acids (norepinephrine)

Babies and hibernating animals have brown fat.

The mitochondria have protein called thermogenin which is activated when its cold thru sym NS. This allow thermogenin to be incorporated into inner membrane. It has a channel and it disrupts the proton gradient. Now you synthesize heat instead of ATP. 

33

Mitochondrial Diseases

Mitochondrial DNA codes for __ ___  (~__%) of the subunits of ___ ____complexes and ATP synthase

Phenotypic effects of mutations reflect ____of tissue to ___ ___

___ ___ ___ most sensitive

Also effects on ___ ___, ____ , ___ ,___

___, ____

Wide variety of symptoms

 

Mitochondrial Diseases

Mitochondrial DNA codes for only some  (~20%) of the subunits of respiratory chain complexes and ATP synthase

Phenotypic effects of mutations reflect reliance of tissue to oxidative phosphorylation

Central nervous system most sensitive

Also effects on skeletal muscle, heart muscle, kidney, liver

Aging, cancer

Wide variety of symptoms

 

34

Leber's hereditary optic neuropathy (LHON)

Causes ___ ____ ____ and ___ ____

Mutations in subunits of ___ ____

Often exhibit ___ ___ ___

Leber's hereditary optic neuropathy (LHON)

Causes loss of vision and cardiac dysrhythmia

Mutations in subunits of NADH dehydrogenase

Often exhibit swollen optic nerve

35

Potential Oxidative Damage

One electron ___ of O2 yields _____anion

Potentially ___ ___; ____ oxygen species

(ROS); _____ damage

Protective Mechanism

 

Degenerative diseases  - _____ _____ ______

From mutations in protective enzymes

 

Electrons can move out of the chain.

Radicals can break down proteins, fats

ROS: Reactive Oxygen Species

ROS dependent aging: As you get older you build up more free radicals and that’s why most of proteins in bodies getting damaged and that increases aging

Potential Oxidative Damage

One electron reduction of O2 yields superoxide anion

Potentially destructive radical; reactive oxygen species

 (ROS); oxidative damage

Protective Mechanism

 

Degenerative diseases  - Parkinson’s, Alzheimer’s and Huntington's

From mutations in protective enzymes

 

Electrons can move out of the chain.

Radicals can break down proteins, fats

ROS: Reactive Oxygen Species

ROS dependent aging: As you get older you build up more free radicals and that’s why most of proteins in bodies getting damaged and that increases aging

36

Summary

Oxidative phosphorylation occurs in _____

Electron transfer through respiratory chain results in___ ____

Proton gradient used to ___ ____

Oxidative phosphorylation ____ by need for ATP

 

Summary

Oxidative phosphorylation occurs in mitochondria

Electron transfer through respiratory chain results in proton gradient

Proton gradient used to synthesize ATP

Oxidative phosphorylation regulated by need for ATP