Ground Rules of Metabolism

Chapter 6

Hsueh-Fen Juan

Oct. 2, 2012

Impacts, Issues:A Toast to Alcohol Dehydrogenase

In the liver, alcohol dehydrogenase helps break down toxic alcohols, but at the expense of liver function and energy metabolism

Video: Alcohol, enzymes, and your liver

6.1 Energy and the World of Life

Assembly of the molecules of life starts with energy input into living cells

Energy Disperses

First law of thermodynamics• Energy is neither created nor destroyed, but can

be transferred from one form to another

Second law of thermodynamics• Entropy (a measure of dispersal of energy in a

system) increases spontaneously• The entropy of two atoms decreases when a

bond forms between them (endergonic reaction)• 熵要仔細看課本

Motion: A Form Of Energy

Entropy

One Way Flow of Energy

The total amount of energy available in the universe to do work, called free energy, is always decreasing• Each time energy is transferred, some energy

escapes as heat (not useful for doing work)• Free energy 和總能量以熵及相關

On Earth, energy flows from the sun, through producers, then consumers• Living things need a constant input of energy

Energy Conversion

Only about 10% of the energy in food goes toward building body mass, most is lost in energy conversions

Fig. 6-5, p. 95

energy input, mainly from sunlight

ENERGY IN

Sunlight energy reaches environments on Earth. Producers of nearly all ecosystems secure some and convert it to stored forms of energy. They and all other organisms convert stored energy to forms that can drive cellular work.

PRODUCERS plants and other self-

feeding organisms

nutrient cycling

ENERGY OUTCONSUMERS

animals, most fungi, many protists, bacteria

With each conversion, there is a one-way flow of a bit of energy back to the environment. Nutrients cycle between producers and consumers.

energy output, mainly heat

Energy Flow

6.2 Energy in the Molecules of Life

All cells store and retrieve energy in chemical bonds of the molecules of life

Free energy• The amount of energy in a molecule that is

available to do work

Energy In, Energy Out

Reaction• A chemical change that occurs when atoms, ions,

or molecules interact

Reactant• Atoms, ions, or molecules that enter a reaction

Product• Atoms, ions, or molecules remaining at the end of

a reaction

Chemical Reactions

Reactions Require or Release Energy

We can predict whether a reaction requires or releases energy by comparing the bond energies of reactants with those of products

Endergonic (“energy in”)• Reactions that require a net input of energy

Exergonic (“energy out”)• Reactions that end with a net release of energy

Endergonic and Exergonic Reactions

Why the World Doesn’t Go Up in Flames

Activation energy• The minimum amount of energy needed to get a

reaction started• Some reactions require a lot of activation energy,

others do not

Activation Energy

ATP – The Cell’s Energy Currency

ATP (adenosine triphosphate)• A nucleotide with three phosphate groups • Transfers a phosphate group and energy to other

molecules

Phosphorylation• A phosphate-group transfer• ADP binds phosphate in an endergonic reaction

to replenish ATP (ATP/ADP cycle)

Fig. 6-9a, p. 97

Fig. 6-9b, p. 97

Fig. 6-9c, p. 97

Animation: Mitochondrial chemiosmosis

6.1-6.2 Key Concepts:Energy Flow in the World of Life

Energy tends to disperse spontaneously; each time energy is transferred, some of it disperses

Organisms maintain their organization only by continuously harvesting energy

ATP couples reactions that release usable energy with reactions that require energy

6.3 How Enzymes Make Substances React

Enzyme• A catalyst that makes a specific reaction occur

much faster than it would on its own• Enzymes are not consumed or changed by

participating in a reaction• Most are proteins, some are RNA

Substrate• The specific reactant acted upon by an enzyme

How Enzymes Work

Enzymes lower the activation energy required to bring on the transition state, when substrate bonds break and reactions run spontaneously

Active sites• Locations on the enzyme molecule where

substrates bind and reactions proceed• Complementary in shape, size, polarity and

charge to the substrate

Active Site of an Enzyme

Fig. 6-10b, p. 98

Fig. 6-10c, p. 98

Activation Energy

Animation: Activation energy

Animation: Enzymes and activation energy

Mechanisms of Enzyme-Mediated Reactions

Binding at enzyme active sites may bring on the transition state by four mechanisms1. Helping substrates get together (拉近距離 )

2. Orienting substrates in positions that favor reaction (有效碰撞 )

3. Inducing a fit between enzyme and substrate (induced-fit model)

4. Shutting out water molecules (隔絕水分子 )

Effects of Temperature, pH, and Salinity

Raising the temperature boosts reaction rates by increasing a substrate’s energy• But very high temperatures denature enzymes

Each enzyme has an optimum pH range• In humans, most enzymes work at ph 6 to 8

Salt levels affect the hydrogen bonds that hold enzymes in their three-dimensional shape

Enzymes and Temperature

Enzymes and pH

Help from Cofactors

Cofactors• Atoms or molecules (other than proteins) that

are necessary for enzyme function• Example: Iron atoms in catalase• 常固定在酶的內部 (或為結構中心 )、反應後不變

Coenzymes• Organic cofactors such as vitamins• May become modified during a reaction• 細胞質內自由飄移，反應後結構常被改變

Catalase and Cofactors

Catalase is an antioxidant that neutralizes free radicals (atoms or molecules with unpaired electrons that attack biological molecules)

自由基很不好，因為容易搶別人電子讓人氧化，隨著年紀增加，體內自由基含量也會增加。抗氧化劑(通常是酶 )藉由中心金屬吸引自由基的未成對電子以「解毒」 (注意！僅吸引，未進行氧化還原 )

Catalase works by holding a substrate molecule close to one of its iron atoms (cofactors)• Iron pulls on the substrate’s electrons, bringing on

the transition state

6.3 Key Concepts:How Enzymes Work

On their own, reactions proceed too slowly to sustain life

Enzymes tremendously increase the rate of metabolic reactions

Environmental factors such as temperature, salt, and pH influence enzyme function

6.4 Metabolism – Organized, Enzyme-Mediated Reactions

ATP, enzymes, and other molecules interact in organized pathways of metabolism (activities by which cells acquire and use energy)

Types of Metabolic Pathways

A metabolic pathway is any series of enzyme-mediated reactions by which a cell builds, rearranges, or breaks down an organic substance• Anabolic pathways build molecules• Catabolic pathways break apart molecules• Cyclic pathways regenerate a molecule from the

first step (例子：光合作用暗反應的卡爾文循環 )

Controls Over Metabolism

Concentrations of reactants or products can make reactions proceed forward or backward

Feedback mechanisms can adjust enzyme production, or activate or inhibit enzymes

Regulatory molecules can bind to an allosteric site to activate or inhibit enzymes (結構變異區 )• Feedback inhibition

Allosteric Control

Animation: Allosteric activation

Animation: Allosteric inhibition

Feedback Inhibition

Animation: Feedback inhibition

Redox Reactions

Oxidation-reduction reactions (paired reactions)• A molecule that gives up electrons is oxidized• A molecule that accepts electrons is reduced• Coenzymes can accept molecules in redox

reactions (also called electron transfers) (電子轉移者、電子攜帶者… etc.) (NADH, FADH2之類 )

ATP Synthesis

細胞不能承受一次放能太多，要讓放能過程拆解成一個個小步驟，而這些小步驟幾乎都是氧化還原反應

Coenzymes deliver electrons to electron transfer chains for ATP synthesis

Electron transfer chain• A series of redox reactions in membrane-

bound enzymes or molecules (特別注意強調固定在膜上的 ) that release energy in small, controlled steps

Uncontrolled and Controlled Reactions

Overview: Energy Pathways

6.4 Key Concepts:The Nature of Metabolism

Metabolic pathways are energy-driven sequences of enzyme-mediated reactions

They concentrate, convert, or dispose of materials in cells

Controls over enzymes that govern key steps in metabolic pathways can shift cell activities fast

6.5 Night Lights

Bioluminescence is visible evidence of metabolism

Bioluminescence• Light emitted from metabolic reactions in living

organisms

Enzymes of Bioluminescence

Bioluminescent organisms emit light when enzymes (luciferases) convert chemical bond energy in luciferins to light energy

luciferin + ATP → luciferin-ADP + Pi

luciferin-ADP + O2 → oxyluciferin + AMP + CO2 + light

Bioluminescence: Fireflies

A Research Connection

Researchers can transfer genes for bioluminescence from one species to another• Example: bacteria with jellyfish genes

6.5 Key Concepts:Metabolism Everywhere

Knowledge about metabolism, including how enzymes work, can help you interpret some natural phenomena

Key Players in Metabolic Reactions