process through which living systems acquire and utilize the free energy they need to carry out their various functions

METABOLISM

etymologymeta: change, transformation

the process by which food is transformed to provide energy

Energyintake

Energyexpenditure

Energy balance

(food intake) (SMR, activities, exercise)

SMR: Standard Metabolic Rate; metabolic rate of an organism not digesting foodat thermoneutrality under resting and stress free conditions.

Metabolic rate: rate of all metabolic reactions (Biochemistry-311)

Negative energy balance

Energyintake Energy

expenditure(food intake)

(SMR, activities, exercise)

anorexia, cachexia, death

Positive energy balance

Energyintake

Energy

expenditure

(food intake)(SMR, activities, exercise)

weight gain, obesity, type 2 diabetes, death

metabolic pathways: series of consecutive enzymatic reactions that produce specific products.

metabolites: reactants, intermediates and products of metabolic pathways

R I I I P

METABOLIC PATHWAYS IN A CELL ROAD MAP

REGULATION, DIRECTIONALITY

METABOLISM = CATABOLISM+ANABOLISM

catabolism (degradation): nutrients and cell constituents are broken down to salvage their components and/or to generate free energy anabolism (biosynthesis): biomolecules are synthesized from simpler components

yin and yang is used to describe how seemingly disjunct or opposing forces are interconnected and interdependent in the natural world giving rise to each other in turn

OVERVIEW OF CATABOLISM

TRANSFORMATION

5 PRINCIPLES OF METABOLIC PATHWAYS

1. metabolic pathways are irreversible2. catabolic and anabolic pathways must differ3. every metabolic pathway has a first committed step4. all metabolic pathways are regulated5. metabolic pathways in eukaryotic cells occur in specific cellular locations

1. METABOLIC PATHWAYS ARE IRREVERSIBLE

A highly exergonic reaction is irreversible. If an exergonic reactionis part of a multistep metabolic pathway, it confers directionality tothe pathway, i.e. it makes the entire pathway irreversible.

R I I I P

2. CATABOLIC AND ANABOLIC PATHWAYS MUST DIFFER

1 2

A

XY

If 2 metabolites are metabolically interconvertible, the pathway fromthe first to the second must be different from the pathway from the second to the first.

3. EVERY METABOLIC PATHWAY HAS A FIRST COMMITTED STEP

Even if metabolic pathways are irreversible, most of the reactions Function close to equilibrium. Early in each pathway there is an Irreversible reaction that commits the intermediate it producesto continue down the pathway.

4. ALL METABOLIC PATHWAYS ARE REGULATED

Metabolic pathways are regulated by laws of supply and demand.

To exert control on the flux of metabolites through a metabolic pathway,it is necessary to regulate its rate-limiting step.

5. METABOLIC PATHWAYS IN EUKARYOTIC CELLS OCCUR IN SPECIFIC CELLULAR LOCATIONS

EXPERIMENTAL APPROACHES TO THE STUDY OF METABOLISM(P.559)

a metabolic pathway can be understood at several levels

1.in terms of the sequence reactions by which a specific nutrient is converted to end products, and the energetics of these conversions2.in terms of the mechanisms by which each intermediate is converted to its successor. Such analysis requires the isolation and characterization of the specific enzymes that catalyze each reaction3.in terms of the control mechanisms that regulate the flow of metabolites through the pathway. An exquisitely complex network of regulatory processes renders metabolic pathways remarkably sensitive to the needs of the organism; the output of a pathway is generally only as great as required.

THERMODYNAMICS OF LIFE

ΔG = ΔGo + RT ln [C] [D][A] [B]

GIBBS FREE ENERGYINDICATOR OF SPONTANEITY

ΔGo

1) indicates the nature of the reaction (compare reactions where all substrates and products are at unit concentrations)2) it is a crude indication of the likelihood of a reaction being physiologically reversible

ΔG

true indication of the direction of a reaction and the likelihood ofits reversibility in vivoΔG = 0 reactions at equilibriumΔG > 0 endergonic, i.e. not spontaneous must be driven by input of free energyΔG < 0 exergonic, i.e. spontaneous processes that can be utilized to do work

THERMODYNAMICS OF LIFEP.574-579

Equilibrium thermodynamics: apply to reversible processes in closed systems. Any isolated system inevitably reaches equilibrium (ΔG=0).

Open systems may remain in a nonequilibrium state as long as they are able to acquire free energy from their surroundings in the form of reactants, heat or work.Open systems rely on the principles of nonequilibrium thermodynamics.

Living organisms are open systems and can never be at equilibrium.Living organisms at equilibrium=death

3 reasons why living organisms must maintain a nonequilibrium state1) only nonequilibrium process can perform useful work2) a process at equilibrium cannot be directed3) living organisms require a constant influx of free energy to be active

LIVING ORGANISMS AND THE STEADY STATE

Living systems are, for the most part, characterized by being in a steady state, meaning that all flows in the system are constant.

The steady state of an open system is its state of maximum thermodynamicefficiency, i.e. it produces the maximum amount of useful work for a given energy expenditure under the prevailing conditions (Ilya Prigogine).

Perturbations from the steady state lead to changes in flows to counteractthese perturbations in order to return to the steady state.

THERMODYNAMICS OF METABOLIC PATHWAYS

Many enzymatic reactions in metabolic pathways function close to equilibrium.

The net rate of these reactions is controlled by changing the concentrationof the substrates and products.

Flux through metabolic pathways is controlled by regulating enzymes thatfunction far from equilibrium (changes in the activity of enzymes).