An introduction to metabolism. Totality of an organisms chemical reactions.

An introduction to metabolism


Totality of an organisms chemical reactions


Totality of an organisms chemical reactions

The chemical factory

Key concepts• An organism’s metabolism transforms matter and

energy, according to the laws of thermodynamics• The free energy change of a reaction tells us

whether the reaction occurs spontaneously• ATP powers cellular work by coupling endergonic

and exergonic reactions• Enzymes speed up chemical reactions• Regulation of enzyme activity helps control

metabolism

Matter review• Something that has mass and occupies space• Matter consists of atoms that are bound together to form molecules• Atoms are never created or destroyed in biological systems (Conservation of matter) but molecules can be

• Definition: Energy is the ability to do work• First law of thermodynamics: Energy cannot be

created or destroyed but, it can be converted to other forms

• Forms

Energy review

Kinetic: energy in motion

Potential: stored energy



• Forms

Energy review

Chemical energy

Kinetic



• Forms

Energy review

Heat and light

Chemical energy



• Second law of thermodynamics: – Some energy becomes unusable with every energy

transfer – Another way to state this: every energy transfer

increases entropy (a measure of disorder and randomness)

– I.e. hot pan and cold sink

Energy review

What does this have to do with metabolism?

MetabolismMetabolism involves metabolic pathways

that change in matter and energy

Begin with a specific molecule which is then altered in a series of defined steps. Each step is catalyzed by an enzyme.

MetabolismMetabolism involves metabolic pathways

that change in matter and energy– Anabolic pathways build complicated

molecules from simple molecules. They consume energy!

– Catabolic pathways breakdown molecules. They release energy!

An organism’s metabolism transforms matter and energy,

according to the laws of thermodynamics

The free energy change of a reaction tells us whether the

reaction occurs spontaneously



The energy available to do work



This means that the reaction does not require energy…it doesn’t necessarily happen fast though.

Free energy change• Unstable systems have a high G, stable

systems have a low G

All systems will go to a more stable state…unless something prevents this from happening

Free energy change• Unstable systems have a high G, stable systems have a

low G

• Change in free energy of a system is symbolized by ∆G• ∆G=G final state - G initial state

• The ∆G is negative when the process involves a loss of free energy. This occurs spontaneously.

All systems will go to a more stable state…unless something prevents this from happening

Equilibrium is the maximum stability

Free energy change and chemical reactions

Exergonic reaction•Proceeds with a net release of energy•∆G is negative•Occurs spontaneously

Endergonic reaction•Absorb free energy•∆G is positive•Not spontaneous (requires energy)

Reactants

Energy

Fre

e e

ne

rgy

Products

Amount ofenergy

released(∆G < 0)

Progress of the reaction

(a) Exergonic reaction: energy released

Products

ReactantsEnergy

Fre

e e

ne

rgy

Amount ofenergy

required(∆G > 0)

(b) Endergonic reaction: energy required


ATP powers cellular work by coupling exergonic and endergonic reactions

Types of cellular work• Chemical work (pushing of endergonic reactions)• Transport work• Mechanical work

Types of cellular work• Chemical work (pushing of endergonic reactions)• Transport work• Mechanical work

Cells accomplish all of these things by energy coupling- using an exergonic reaction to drive an endergonic one

ATP is usually involved•Adenine triphosphate•Contains a ribose sugar, adenosine, and three phosphate groups•Bonds with phosphate groups can be broken to release energy (generates ADP + Pi)

How ATP performs chemical workTypically ATP aids in the

driving endergonic chemical reactions through phosphorylation– Transfers a

phosphate group to the reactant

– Reactant becomes unstable

– Reactant reacts forming a new product

Ammonia displacesthe phosphate group,forming glutamine.

PP

GluNH3

NH2

Glu i

GluADP+

PATP+

+

Glu

ATP phosphorylatesglutamic acid,making the aminoacid less stable.

GluNH3

NH2

Glu+

Glutamicacid

GlutamineAmmonia

∆G = +3.4 kcal/mol

+

1

How ATP performs transport and mechanical work

(b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzed

Membrane protein

P i

ADP+

P

Solute Solute transported

P i

Vesicle Cytoskeletal track

Motor protein Protein moved

(a) Transport work: ATP phosphorylates transport proteins

ATP

ATP

Regeneration of ATP

P iADP +

Energy fromcatabolism (exergonic,energy-releasingprocesses)

Energy for cellularwork (endergonic,energy-consumingprocesses)

ATP + H2O

ATP powers cellular work by coupling exergonic and endergonic reactions

Enzymes speed up metabolic reactions by lowering

energy barriers


energy barriers

A macromolecule, typically a protein, that speeds up a chemical reaction without being used up

Activation energy • All chemical reactions involve bond

formation and breaking

• Bonds need to be in an unstable (high free energy state) to change

• An initial investment in energy is required to destabilize bonds

• New bonds formed will be more stable (energy is released)

Activation energy


Products

Reactants

∆G < O

Transition state

Fre

e en

erg

y EA

DC

BA

D

D

C

C

B

B

A

A

Even in exergonic reactions, activation energy is a barrier

How do enzymes function?• Substrate binds to the

enzyme’s active site • Substrate specificity is

based on protein shape• While they are bound the

enzyme converts the reactant to the product

• After the product is created, the enzyme releases it and can catalyze another reaction

• Most metabolic reactions are reversible, the same enzyme can catalyze the reverse reaction

Substrates

Enzyme

Products

Enzyme-substratecomplex

2

How does this interaction speed up the rate of a chemical reaction?

• Enzymes orient reactants properly for the reaction to occur

• Enzymes can stretch the substrate (causing unstable bonds)

• Enzymes can create micro environments

• The active site can participate directly in the chemical reaction

Substrates

Enzyme

Products

Enzyme-substratecomplex

2

Remember, proteins are sensitive to environmental conditions

Ra

te o

f re

ac

tio

n

Optimal temperature forenzyme of thermophilic

(heat-tolerant) bacteria

Optimal temperature fortypical human enzyme

(a) Optimal temperature for two enzymes

(b) Optimal pH for two enzymes

Ra

te o

f re

ac

tio

n

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

Temperature (ºC)

pH543210 6 7 8 9 10

0 20 40 80 60 100

What other factors impact enzyme function?

Cofactors-non-protein helpers aid catalytic activity– If organic called a

coenzyme

i.e. Catalase, an antioxidant that neutralizes free radicals in the cell, contains an iron atom which aids in bringing the substrate to the transition state

What other factors impact enzyme function?

Inhibitors• Competitive inhibitors bind to the enzyme’s active site• Non-competitive inhibitors bind elsewhere on the

molecule, but change the shape of the active site • Can be reversible or irreversible (impacts can very)

(a) Normal binding (c) Noncompetitive inhibition(b) Competitive inhibition

Noncompetitive inhibitor

Active siteCompetitive inhibitor

Substrate

Enzyme


energy barriers

Regulation of enzyme activity helps control metabolism


• Allosteric

• Cooperativity

• Positive and negative feedbacks


Cells can regulate biochemical pathways by

• Making more or less of an enzyme• Regulating enzyme function

– Cooperativity• Substrate bind to the active site of one

subunit of a multi sub-unit enzyme

• Amplifies the catalytic response

– Allosteric regulation• similar to non-competitive inhibition

(molecules bind at an allosteric site to alter the shape of the active site)

• Can inhibit or stimulate enzyme function

Allosteric enyzmewith four subunits

Active site(one of four)

Regulatorysite (oneof four) Active form

ActivatorStabilized active form

Oscillation

Non-functionalactivesite

InhibitorInactive form Stabilized inactive

form

(a) Allosteric activators and inhibitors

Substrate

Inactive form Stabilized activeform


Feedback

regulation

Negativefeedback

Excess Dblocks a step

D

D D

A

B

C

Enzyme 1

Enzyme 2

Enzyme 3

D

(a) Negative feedback

W

Enzyme 4

XPositivefeedback

Enzyme 5

Y

+

Enzyme 6

Excess Zstimulates astep

ZZ

Z

Z

(b) Positive feedback

Key concepts• An organism’s metabolism transforms matter and energy,

according to the laws of thermodynamics• The free energy change of a reaction tells us whether the

reaction occurs spontaneously• ATP powers cellular work by coupling endergonic and

exergonic reactions• Enzymes speed up chemical reactions• Regulation of enzyme activity helps control metabolism

Concept map

Water

Hydrogen bonds

High specific heat

Cohesion

Water

Hydrogen bonds

High specific heat Cohesion

forms

give water special properties including

Concept map

Metabolism concept map

Metabolism

Metabolic pathway

Enzyme inhibitor

Enzymes

Cooperativity

Allosteric

Feedback

Chemical reaction

anabolic

Catabolic

Metabolic regulation

cell

Endergonic

Exergonic

ATP

An introduction to metabolism. Totality of an organisms chemical reactions.

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Transcript of An introduction to metabolism. Totality of an organisms chemical reactions.