METABOLISM OVERVIEW
METABOLISM
• The sum of all reactions occurring in an organism, includes:
• catabolism, which are the reactions involved in the
breakdown of biomolecules.
• anabolism, which are the reactions involved in the
synthesis of biomolecules.
• A metabolic pathway is a sequence
of reactions used to produce one
product or accomplish one process.
CATABOLISM OF FOOD
• The catabolism of food is a three stage process.
• Stage I: Large, complex molecules are digested into
simpler ones, using hydrolysis reactions.
CATABOLISM OF FOOD (continued)
• Stage II: Small molecules are broken down into simpler units,
usually two carbon portion of acetyl CoA.
• Stage III: The “common catabolic pathway” extracts energy to
produce ATP.
CATABOLISM OF FOOD (continued)
CARBOHYDRATE CATABOLISM
CARBOHYDRATE METABOLISM (DIGESTION)
• The main reaction of carbohydrate digestion to
monosaccharides is hydrolysis:
Glucose Metabolism Overview
Glycogen
Glycogenesis
High glucose present, β
cells in pancreas
realease insulin
Ribose
RNA
Polysaccharide
Energy Storage
Glycogenolysis
Muscles need energy or
fear, anger conditions or
absence of glucose
Glucose
Gluconeogensis
During starvation 
breakdown of proteins
from muscle cells
Glycolysis
10 step process
Pyruvate
Energy
GLYCOLYSIS
• Glucose (C6) is catabolically oxidized through a many step
process to pyruvate (C3).
• In addition to the two molecules of pyruvate, two molecules
of ATP, two molecules of NADH, four molecules of H+, and
two molecules of H2O are produced.
• Glycolysis occurs in the cellular cytoplasm.
• Net reaction for glycolysis:
GLYCOLYSIS
(continued)
GLYCOLYSIS
(continued)
GLYCOLYSIS – REGULATION (continued)
THE FATES OF PYRUVATE (continued)
PYRUVATE OXIDATION TO ACETYL CoA
• Pyruvate oxidation to acetyl CoA occurs in the mitochondria.
• Most of the acetyl CoA will be completely oxidized to CO2 in
the citric acid cycle.
• Some acetyl CoA will serve as starting material for fatty acid
biosynthesis.
• NAD+ is regenerated when NADH transfers its electrons to
O2 in the electron transport chain.
PYRUVATE REDUCTION TO LACTATE
• Pyruvate reduction to lactate occurs in cells after strenuous
or long-term muscle activity because the cellular supply of
oxygen is not adequate for the reoxidation of NADH to NAD+.
• Under anaerobic conditions, animals and some
microorganism can obtain limited energy through lactate
fermentation.
PYRUVATE REDUCTION TO ETHANOL
• Under anaerobic conditions, some microorganisms can
obtain limited energy through glycolysis and the two step
conversion of pyruvate to ethanol.
• Overall equation:
• Step-wise equations:
LIPID CATABOLISM
LIPID METABOLISM – BLOOD LIPIDS
• During digestion, lipids are
hydrolyzed to glycerol, fatty
acids, and monoglycerides.
• For transport in the lymph
and blood, the cells of the
small intestines produce
lipoprotein aggregates called
chylomicrons.
BLOOD LIPID CLASSIFICATION
• Lipids are less dense than proteins.
• The classification of blood lipids is based on density.
• The higher the lipid concentration of a lipoprotein aggregate,
the lower the density.
VLDL = very low density lipoprotein
LDL = low density lipoprotein
HDL = high density lipoprotein
SCHEMATIC MODEL OF LDL
GLYCEROL METABOLISM
• Glycerol can be converted to dihydroxyacetone phosphate,
an intermediate of glycolysis.
• Glycerol can be converted to pyruvate and contribute to
cellular energy production.
• Pyruvate can be converted to glucose through
gluconeogenesis.
FATTY ACID OXIDATION
Activation Step:
• Before fatty acids can be catabolized, they must be activated
by conversion to fatty acyl CoA.
• The conversion to fatty acyl CoA is catalyzed by acyl CoA
synthetase.
FATTY ACID OXIDATION (continued)
FATTY ACID OXIDATION (continued)
O
O
CH3(CH2)14-C-CH2-C-S-CoA
FATTY ACID OXIDATION (continued)
• Stearic acid:
• makes eight passes through -oxidation sequence.
• produces nine molecules of acetyl CoA.
• produces eight molecules FADH2.
• produces eight molecules of NADH.
FATTY ACID OXIDATION (continued)
• In the last spiral, the four-carbon chain of butyryl CoA
passed through the -oxidation sequence, and produces:
• one molecule FADH2,
• one molecule NADH,
• and two molecules of acetyl CoA.
KEY NUMBERS FOR ATP CALCULATIONS
• Determine the number of acetyl CoA molecules:
number of fatty acid carbons
acetyl CoA 
2
• Determine the number of trips through the fatty acid spiral
(one less than the number of acetyl CoA molecules):
• Multipliers:
• every acetyl CoA = 10 ATP molecules
• every NADH = 2.5 ATP molecules
• every FADH2 = 1.5 ATP molecules
KEY NUMBERS FOR ATP CALCULATIONS
(continued)
• Example for 10-carbon fatty acid (five acetyl CoA molecules,
four trips through fatty acid spiral):
(5 acetyl CoA) × 10
(4 NADH + H+) × 2.5
(4 FADH2) × 1.5
Activation step
Total ATP
= 50 ATP
= 10 ATP
= 6 ATP
= −2 ATP
= 64 ATP
ENERGY FROM FATTY ACIDS (continued)
• The amount of energy produced from stearic acid (C18):
KEY COMPONENTS IN
CATABOLISM
ATP – THE PRIMARY ENERGY CARRIER
(continued)
• ATP hydrolysis releases a great amount of free energy:
• ATP is a high-energy compound (liberates a great amount
of free energy on hydrolysis).
ATP – THE PRIMARY ENERGY CARRIER
(continued)
ATP-ADP CYCLE
• Supplies cellular energy
ATP FORMATION
• ATP formation occurs on the inner membrane of
mitochondria (cellular organelle where reactions of the
common catabolic pathway occur).
IMPORTANT COENZYMES – COENZYME A
• Coenzyme A is a central compound in metabolism, it is part
of acetyl CoA.
• It is derived from the B vitamin pantothenic acid.
• It contains a reactive sulfhydryl group (CoA-SH).
• It forms a thioester bond with an acetyl group or other acyl
groups.
• Acetyl CoA is the primary fuel for citric acid cycle.
IMPORTANT COENZYMES – NAD+
• Nicotinamide
adenine
dinucleotide (NAD+)
is a derivative of
ADP and the vitamin
nicotinamide.
NAD+
• NAD+ acts as an electron acceptor.
NAD+ (continued)
• NAD+ is important in the oxidation of many biomolecules.
IMPORTANT COENZYMES – FAD
• Flavin adenine
dinucleotide (FAD) is
derived from ADP
and the vitamin
riboflavin.
FAD
• FAD acts as an electron acceptor.
FAD (continued)
• FAD is often involved in the oxidation of –CH2–CH2– to
–CH=CH– bonds.
CITRIC ACID CYCLE
(KREBS CYCLE)
THE CITRIC ACID CYCLE
• The citric acid cycle:
• has other names, including:
• the tricarboxylic acid cycle.
• the Krebs cycle.
• is the principle process for generating the reduced
coenzymes NADH and FADH2.
• is the source of intermediates for biosynthesis.
• occurs within the matrix of the mitochondrion.
• includes eight reactions.
THE CITRIC ACID CYCLE (continued)
• Pyruvate oxidized to acetyl CoA can enter the citric acid
cycle where it will be further oxidized to two molecules of
CO2, producing one molecule of GTP and the reduced forms
of three molecules of NAD+ (NADH) and one molecule of
FAD (FADH2) which can then enter the electron transport
chain to produce ATP.
• The overall reaction is:
THE CITRIC ACID CYCLE (continued)
THE CITRIC ACID CYCLE (continued)
THE CITRIC ACID CYCLE (continued)
CITRIC ACID CYCLE – REGULATION
(continued)
•The rate of citric acid cycle is reduced
when cellular ATP levels are high.
•The rate of citric acid cycle is increased
when ATP supplies are low and ADP levels
are high.
THE ELECTRON TRANSPORT CHAIN
• NADH and FADH2 are produced by the citric acid cycle.
• They enter the electron transport chain where they can be
used to supply hydrogen ions and electrons to reduce
oxygen to water.
• Net equation:
4H+ + 4e− + O2 → 2H2O
• The electron transport chain occurs in a series of reactions.
THE ELECTRON TRANSPORT CHAIN
(continued)
• The electron transport chain is found in the inner
membrane of the mitochondria and involves iron-containing
enzymes (cytochromes).
THE ELECTRON TRANSPORT CHAIN
(continued)
• As electrons are
transported along the
electron transport
chain, a significant
amount of free energy
is released (52.6
kcal/mol).
• Some free energy is
conserved in oxidative
phosphorylation
(production of ATP from
ADP and Pi).
OXIDATIVE PHOSPHORYLATION:
CHEMIOSMOTIC HYPOTHESIS
• The chemiosmotic hypothesis states that the electron
transport chain pumps H+ across the inner mitochondrial
membrane, H+ then flows back across the membrane,
causing the formation of ATP by F1-ATPase.
• Oxidative phosphorylation conserves approximately 34%
of the energy released from the electron transport chain for
each mole of NADH.
• Oxidative phosphorylation conserves approximately 25%
of the energy released from the electron transport chain for
each mole of FADH2.
OXIDATIVE PHOSPHORYLATION:
CHEMIOSMOTIC HYPOTHESIS
OXIDATIVE PHOSPHORYLATION FROM
ELECTRON TRANSPORT
• The conversion of NADH to NAD+ generates 2.5 ATP from
ADP during oxidative phosphorylation.
• The conversion of FADH2 to FAD generates 1.5 ATP from
ADP during oxidative phosphorylation.
• The energy yield for the entire catabolic pathway (citric acid
cycle, electron transport chain, and oxidative
phosphorylation combined):