Essential Biochemistry

Lecture Notes for Chapter 12

Metabolism and Bioenergetics

Essential BiochemistryThird Edition

Charlotte W. Pratt | Kathleen Cornely

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.

Overview of Metabolism

Breaking downmolecules

Building upmolecules

Free energy comes from hydrolysis of ATP

© 2014 John Wiley & Sons, Inc. All rights reserved.

Cells take up the products of digestion.

• Human diet consists of four types of biomolecules– Proteins– Nucleic acids– Polysaccharides– Fats (particularly triacylglycerols)

• Digestion reduces biomolecules to monomers– Amino acids– Nucleotides– Monosaccharides– Fatty acid


Starchy foods are hydrolyzed by amylases.

Bond broken

Amylasesare found in the salivary glands


Proteins are hydrolyzed by proteases.

Proteases are secreted in the stomach and pancreas.


Fatty acids are hydrolyzed by lipases.

Remember: Fatty acids are technically not

polymers.

Lipases are made in the

pancreas and secreted in the

small intestines.


Monomers are stored as polymers.Fatty acids are stored in the formof triacylglycerols (large globules)in adipocytes.


Some tissues use monosaccharides to produce glycogen.

Glycogen Structure

Electron Micrograph of a Liver Cell

GlycogenGranules

(pink)

Fat Globule(yellow)

Mitochondria(green)


Glycogen breakdown occurs via phosphorolysis.


Proteins are degraded by proteases or by the proteasome.

The inner chamber of the proteasome is

where proteolytic cleavage occurs.


Proteins being degraded in the proteasome are

tagged with a small protein called

ubiquitin.


Protein Degradation by the Proteasome


Some major metabolic pathways share a few common intermediates.


Some major metabolic pathways share a few common intermediates.

Glucose Catabolism


Many metabolic pathways include oxidation-reduction reactions.

• Catabolism of amino acids, monosaccharides, and fatty acids involves oxidizing carbon.

• Anabolism of amino acids, monosaccharides, and fatty acids involves reducing carbon.

Carbon in methane is most highly reduced.

Carbon in CO2is most highly

oxidized.


Carbons in fatty acids and carbohydrates are oxidized to CO2.

Fatty acids have many methylene

carbons that undergo

oxidation.

Carbohydrates have (CH2O) carbons that

undergo oxidation.


Some cofactors undergo oxidation-reduction.

• Recall definitions of oxidation and reduction.– Oxidation = loss of electrons– Reduction = gain of electrons

• Electrons can get passed from metabolites to enzyme cofactors such as NAD+ or NADP+.


Electrons are transferred from ubiquinone to ubiquinol in a

stepwise manner.


Cofactors are recycled through oxidative phosphorylation.


Overview of Metabolism

• Monomers are formed.• Intermediates with two or three

carbons are formed.• Carbons are fully oxidized to

CO2.

• Electron carriers gain electrons.• Electron carriers are recycled

via electron loss.• ATP and H2O are produced.


Humans do not synthesize some important biomolecules.


Humans do not synthesize vitamins.


Humans do not synthesize vitamins.


The free energy change depends on reactant concentrations.

Standard Free Energy

Change


Biochemical measurements for ΔG°' are valid under standard conditions.

What happens when the experimental conditions are not “standard”?© 2014 John Wiley & Sons, Inc. All rights reserved.

Actual free energy changes are related to ΔG°'.

Standard Free Energy

Change

Actual Free Energy

Change

Sometimes called the “mass action ratio”

Used to determinereaction spontaneity


Reaction Spontaneity

• When ΔG >>0:– Reaction is not spontaneous.– Reaction is unfavorable.

• When ΔG<<0:– Reaction is spontaneous.– Reaction is favorable.

• Unfavorable reactions are sometimes coupled with favorable reactions in metabolism.


Consider the following reactions.

A highly favorable reaction

A highly unfavorable reaction© 2014 John Wiley & Sons, Inc. All rights reserved.

ATP hydrolysis provides the energy for glucose phosphorylation.

The ΔG°' values for each reaction are added to give the ΔG°' value

for the coupled reaction.

The net reaction has a negative ΔG°’, which is favorable!


What’s so special about ATP?

• ATP hydrolysis drives many unfavorable reactions to completion.

• As a result, ATP acts as “energy currency”.


ATP is often involved in coupled processes.

Cleavage of phosphoanhydride

bonds yields energy to drive

unfavorable reactions.


Why does ATP hydrolysis release so much energy?

• ATP hydrolysis products are more stable than the reactants.

• A compound with a phosphoanhydride bond experiences less resonance stabilization than its products. Less Stable More Stable


Several different molecules can serve as energy currency within a cell.


Thioester hydrolysis also releases a large amount of free energy.

• Recall: Coenzyme A is a nucleotide derivative.• Thioesters have less resonance stability than oxygen

esters. – Thioester hydrolysis is more exergonic than oxygen

ester hydrolysis.

ΔG°’ = -31.5 kJmol-1


Regulation occurs at steps with the largest free energy changes.

Cells can regulate flux through a pathway by adjusting the rate of a reaction with a large free energy change.


Review of Metabolism

Breaking downmolecules

Building upmolecules

Oxidation Reduction

ATP

Protein, Fat, Glycogen, Nucleic acids

Pyruvate, Acetyl-CoA

電子釋出電子吸收

電子的貨幣

大分子

電子的媒介NADH

電子的媒介NADH, NADPH

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Essential Biochemistry