Chapter seven
Introduction to Metabolism
Introduction:
• Living organisms must work to stay alive, to grow and to
reproduce.
• All living organisms have the ability to produce energy and to
channel it into biological work.
• Living organisms carry out energy transductions, conversions of
one form of energy to another form.
• Organisms use the chemical energy in fuels (carbonhydrates,
lipids) to bring about the synthesis of complex macromolecules
from simple precursors.
• The field of biochemistry concerned with the transformation and
use of energy by living cells is called bioenergetics.
• The chemical reactions occurring in living beings (or biochemical
reactions) are associated with the liberation of energy as the
reacting system moves from a higher to a lower energy level.
• Metabolism (from Greek metabolē – a change) is a set of all
chemical reactions taking place in organism.
Metabolic pathways
• The fate of dietary components after digestion and absorption
constitutes metabolism—the metabolic pathways taken by individual
molecules, their interrelationships, and the mechanisms that regulate
the flow of metabolites through the pathways. Metabolic pathways
fall into three categories:
(1) Anabolic pathways are those involved in the synthesis of
compounds. Protein synthesis is such a pathway, as is the synthesis of
fuel reserves of triacylglycerol and glycogen. Anabolic pathways are
endergonic.
(2) Catabolic pathways are involved in the breakdown of larger
molecules, commonly involving oxidative reactions; they are exergonic,
producing reducing equivalents and, mainly via the respiratory chain,
ATP.
(3) Amphibolic pathways occur at the “crossroads” of metabolism,
acting as links between the anabolic and catabolic pathways, eg, the
citric acid cycle.
Catabolic pathways
• Catabolism can be divided into the four stages.
• Stage 1: Bulk food is hydrolyzed in the stomach and small intestine
to give small molecules.
• Stage 2: Fatty acids, monosaccharides, and amino acids are
degraded in cells to yield acetyl CoA.
• Stage 3: Acetyl CoA is oxidized in the citric acid cycle to give
CO2.
• Stage 4 The energy released in the citric acid cycle is used by the
electron transport chain to oxidatively phosphorylated ADP and
produce ATP.
 In the first catabolic stage, commonly called digestion, food is
broken down in the mouth, stomach, and small intestine by
hydrolysis of ester, acetal (glycoside), and amide (peptide) bonds to
yield fatty acids, simple sugars, and amino acids.
 These smaller molecules are then absorbed and further degraded in
the second stage of catabolism to yield acetyl groups attached by a
thioester bond to the large carrier molecule coenzyme A.
 The resultant compound, acetyl coenzyme A (acetyl CoA), is a key
substance in the metabolism of food molecules and in many other
biological pathways.
 As shown below, the acetyl group in acetyl CoA is linked to the
sulfur atom of phosphopantetheine, which is itself linked to
adenosine 3′,5′bisphosphate.
• Acetyl groups are oxidized inside cellular mitochondria in the
third stage of catabolism, the citric acid cycle, to yield CO2.
• Like most oxidations, this stage releases a large amount of
energy, which is used in the fourth stage, the electrontransport
chain,
to
accomplish
the
endergonic
phosphorylation of adenosine diphosphate (ADP) with
hydrogen phosphate ion (HOPO3-2, abbreviated Pi) to give
adenosine triphosphate (ATP).
• As the final result of food catabolism, ATP has been called the
“energy currency” of the cell.
• Catabolic reactions “buy” ATP by using the energy they release to
synthesize it from ADP plus hydrogen phosphate ion.
• Anabolic reactions then spend the ATP by transferring a phosphate
group to another molecule, thereby regenerating ADP.
• Energy production and use in living organisms thus revolves around
the ATP ↔ ADP interconversion.
• ADP and ATP are both phosphoric acid anhydrides, which contain
linkages analogous to the
linkage in carboxylic
acid anhydrides.
• Just as carboxylic acid anhydrides react with alcohols by breaking a
C-O bond and forming a carboxylic ester, ROCOR′, phosphoric acid
anhydrides react with alcohols by breaking a P-O bond and forming a
phosphate ester, ROPO3-2.
• The reaction is, in effect, a nucleophilic acyl substitution at
phosphorus.
• Note that phosphorylation reactions with ATP generally require the
presence of a divalent metal cation in the enzyme, usually Mg+2, to
form a Lewis acid–base complex with the phosphate oxygen atoms
and neutralize negative charge.
Nucleophilic substitution reaction of ATP
Bioenergetics
• Bioenergetics, or biochemical thermodynamics, is the study of the
energy changes accompanying biochemical reactions.
• Biological systems are essentially isothermic and use chemical
energy to power living processes.
• How an animal obtains suitable fuel from its food to provide this
energy is basic to the understanding of normal nutrition and
metabolism.
• Death from starvation occurs when available energy reserves are
depleted, and certain forms of malnutrition and associated with
energy imbalance (marasmus).
• Thyroid hormones control the rate of energy release (metabolic
rate), and disease results when they malfunction.
• Excess storage of surplus energy causes obesity.
Concept of free energy
• Free energy (∆G) is that portion of the total energy change in a
system that is available for doing work, i.e., the useful, also known
as the “energy present in the chemical bonds of the system”.
Endergonic and exergonic reactions:
• If ∆G is negative (the free energy of products is less than the
reactants in the system), the reaction proceeds spontaneously with
loss of free energy: i.e., it is exergonic.
• On the other hand, if ∆G is positive (the free energy of the products
is greater than the reactants in the system), the reaction proceeds
only if the free energy can be gained; i.e., it is endergonic.
Coupled reactions in metabolism
• Metabolism is essentially a linked series of chemical reactions that
begins with a particular molecule and converts it into some other
molecule or molecules in a carefully defined fashion.
• Metabolic
reactions
are
often
coupled
together
to
form metabolic pathways, where one substance is transformed,
through a series of reactions, into another one.
• A pathway must satisfy minimally two criteria:
(1) the individual reactions must be specific and
(2) the entire set of reactions that constitute the pathway must
be thermodynamically favored.
i.e, The free-energy change ∆G must be negative and energy must be
released for a reaction to be favorable and occur spontaneously.
• If ∆G is positive, the reaction is energetically unfavorable and the
process can’t occur spontaneously.
•
.
• For an energetically unfavorable reaction to occur, it must be
“coupled” to an energetically favorable reaction so that the overall
free-energy change for the two reactions together is favorable.
• Taking the two reactions together, they share, or are coupled through,
the common intermediate n, which is a product in the first reaction
and a reactant in the second.
• That is, the two reactions added together have a favorable ∆G<0,
and we say that the favorable reaction 2 “drives” the unfavorable
reaction 1. Because the two reactions are coupled through n, the
transformation of A to B becomes favorable.
• Phosphorylation reaction of glucose to yield glucose 6-phosphate
plus water, an important step in the breakdown of dietary
carbohydrates.
• The reaction of glucose with HOPO3-2 does not occur spontaneously
because it is energetically unfavorable, with ∆G°′ +13.8 kJ/mol.
(The standard free energy change for a biological reaction is denoted
∆G°′ and refers to a process in which reactants and products have a
concentration of 1.0 M in a solution with pH =7).
Problem 29.1
• One of the steps in fat metabolism is the reaction of glycerol (1,2,3propanetriol) with ATP to yield glycerol 1-phosphate. Write the
reaction, and draw the structure of glycerol 1-phosphate.
ATP Is the Universal Currency of Free Energy in
Biological Systems
• ATP is an energy-rich molecule because its triphosphate unit
contains two phosphoanhydride bonds. A large amount of free
energy is liberated when ATP is hydrolyzed to adenosine
diphosphate (ADP) and hydrogen phosphate (Pi) or when ATP is
hydrolyzed to adenosine monophosphate (AMP) and pyrophosphate
(PPi).