Metabolism
• Total of all chemical changes that occur in
body. Includes:
– Anabolism: energy-requiring process where small
molecules joined to form larger molecules
• E.g. Glucose + Glucose
– Catabolism: energy-releasing process where
large molecules broken down to smaller
• Energy in carbohydrates, lipids, proteins is
used to produce ATP through oxidation-
reduction reactions
Metabolic Pathways
• The enzymatic reactions of
metabolism form a network of
interconnected chemical reactions,
or pathways.
• The molecules of the pathway are
called intermediates because the
products of one reaction become the
substrates of the next.
• Enzymes control the flow of energy
through a pathway.
Intermediary Metabolism
Oxidation-Reduction Reactions
• Oxidation occurs via the loss of hydrogen or the
gain of oxygen
• Whenever one substance is oxidized, another
substance is reduced
• Oxidized substances lose energy
• Reduced substances gain energy
• Coenzymes act as hydrogen (or electron)
acceptors
• Two important coenzymes are nicotinamide
adenine dinucleotide (NAD+) and flavin adenine
dinucleotide (FAD)
Stages of Metabolism
• Energy-containing nutrients are
processed in three major stages:
1. Digestion – breakdown of
food; nutrients are transported to
tissues
2. Anabolism and formation of
catabolic intermediates where
nutrients are:
• Built into lipids, proteins,
and glycogen or
• Broken down by catabolic
pathways to pyruvic acid and
acetyl CoA.
3. Oxidative breakdown –
nutrients are catabolized to carbon
dioxide, water, and ATP
Figure 24.3
Carbohydrate Metabolism
• Since all carbohydrates are transformed into glucose,
it is essentially glucose metabolism
• Oxidation of glucose is shown by the overall reaction:
C6H12O6 + 6O2 6H2O + 6CO2 + 36 ATP + heat
• Glucose is catabolized in three pathways
– Glycolysis
– Krebs cycle
– The electron transport chain and oxidative
phosphorylation
Carbohydrate Catabolism
Figure 24.5
Glycolysis
• A three-phase pathway in which:
– Glucose is oxidized into pyruvic acid (PA)
• It loses 2 pairs of hydrogens
– NAD+ is reduced to NADH + H+
• It accepts 2 pairs of hydrogens lost by glucose
– ATP is synthesized by substrate-level
phosphorylation
• Pyruvic acid: end-product of glycolysis
– Moves on to the Krebs cycle in an aerobic
pathway (i.e. sufficient oxygen available to cell)
– Is reduced to lactic acid in an anaerobic
environment (insufficient O2 available to cell)
– pyruvic acid lactic aicd
Glycolysis
Figure 24.6
Glycolysis: Phase 1 and 2
• Phase 1: Sugar activation
– Two ATP molecules activate glucose into
fructose-1,6-diphosphate
• The 1 and 6 indicate which carbon atom to
which they are attached.
• Phase 2: Sugar cleavage (splitting)
– Fructose-1,6-bisphosphate (6 C‟s) is split
into two 3-carbon compounds:
• Glyceraldehyde 3-phosphate (GAP)
Glycolysis: Phase 3
• Phase 3: Oxidation and ATP formation
– The 3-carbon sugars are oxidized (reducing
NAD+); i.e., 2 H‟s + NAD NADH2
– Inorganic phosphate groups (Pi) are attached
to each oxidized fragment
– The terminal phosphates are cleaved and
captured by ADP to form four ATP molecules
– The final products are:
• Two pyruvic acid molecules
• Two NADH + H+ molecules (reduced NAD+)
• A net gain of two ATP molecules
Figure 3-41
Glycolysis: A
net gain of 2
molecules of
ATP and 4
atoms
of hydrogen.
Krebs Cycle: Preparatory Step
• Occurs in the mitochondrial matrix and is fueled by
pyruvic acid and fatty acids
• Pyruvic acid from glycolysis is converted to acetyl
coenzyme A (A-CoA) in three main steps:
– Decarboxylation
• 1 carbon is removed from pyruvic acid; 3C 2C molecule
• The lost carbon forms carbon dioxide; exhaled
– Oxidation
• 2 Hydrogen atoms are removed from pyruvic acid („oxidation‟)
and picked up by NAD
• NAD+ is reduced to NADH + H+ (see next slide)
– Formation of acetyl CoA – the resulting acetic acid is combined
with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA
(ACoA)
Figure 3-43
Each transition of pyruvate
to acetyl coenzyme A yields
one NADH and one CO2.
The acetyl coenzyme A
then enters the Krebs cycle.
Krebs Cycle
• An eight-step cycle in which each acetic acid is
decarboxylated and oxidized, generating:
– Three molecules of NADH + H+ (ox/red)
– One molecule of FADH2 (ox/red)
– Two molecules of CO2 (decarboxylation)
– One molecule of ATP (substrate level
phosphorylation
• For each molecule of glucose entering glycolysis,
two molecules of acetyl CoA enter the Krebs
cycle
– Remember, 1 6 C Glucose 2-2 carbon
acetyl coenzyme A (A-CoA)
Krebs Cycle
Figure 24.7
Electron Transport Chain
• Food (glucose) is oxidized and the released hydrogens:
– Are transported by coenzymes NADH and FADH2
– Enter a chain of proteins bound to metal atoms
(cofactors)
– Combine with molecular oxygen to form water
– Release energy
• The energy released is harnessed to attach inorganic
phosphate groups (Pi) to ADP, making ATP by oxidative
phosphorylation
– “phosphorylation” - to add phosphate to a substance
» ADP + P ATP
Mechanism of Oxidative Phosphorylation
• The hydrogens delivered to the chain are split into protons
(H+) and electrons
– The protons are pumped across the inner mitochondrial
membrane to the intermembrane space
– This creates a pH and concentration gradient (of H+)
– The electrons are shuttled from one acceptor to the next
• Electrons are delivered to oxygen, forming oxygen ions
• Oxygen ions attract H+ that were pumped into the
intermembrane space to form water
• H+ that were pumped to the intermembrane space:
– Diffuse down their gradients back to the matrix via ATP
synthase (from greater to lesser concentration)
– Release energy to make ATP
Electron-Transport Chain
ATP Synthase
• The enzyme
consists of three
parts: a rotor, a
knob, and a rod
• Current created
by H+ causes the
rotor and rod to
rotate
• This rotation
activates catalytic
sites in the knob
where ADP and Pi
are combined to
make ATP
Anaerobic Respiration
• Breakdown of glucose
in absence of oxygen
– Produces 2 molecules
of lactic acid and 2
molecules of ATP
• Phases
– Glycolysis
– Lactic acid formation
Lipid Metabolism
• Most products of fat metabolism are transported in
lymph as chylomicrons
• Lipids in chylomicrons are hydrolyzed by plasma
enzymes and absorbed by cells
• Only neutral fats are routinely oxidized for energy
• Catabolism of fats involves two separate pathways
– Glycerol pathway
– Fatty acids pathway
Lipolysis
via
b-oxidation
Lipid Synthesis
Protein Metabolism
• Non-essential amino acids can be formed by
transamination, transfer of an amine group
to keto acid. Can also be eaten.
• If used for energy, amino acids undergo
oxidative deamination. Ammonia and keto
acids are produced as by-products of
oxidative deamination. Ammonia is
converted to urea and excreted.
• Amino acids are not stored in the body
Protein Catabolism
Interconversion of Nutrient
Molecules
• Glycogenesis
– Excess glucose used to form glycogen
• Lipogenesis
– When glycogen stores filled, glucose and amino acids used
to synthesize lipids
• Glycogenolysis
– Breakdown of glycogen to glucose
• Gluconeogenesis
– Formation of glucose from amino acids and glycerol
Interconversion of Nutrient
Molecules
Summary: Carbohydrate
Metabolic Reactions
Table 24.2.1
Summary: Lipid and Protein
Metabolic Reactions
Table 24.2.2