Figure 23-1 The processes of catabolism and Figure 23-2 A schematic representation of a
Biochemical Metabolism
Chapter 23
Outline
23.1 Metabolism
23.2 Metabolism and cell structure
23.3 Important nucleotide-containing compounds in metabolic
pathwaysy
23.4 Important carboxylate ions in metabolic pathways
23.5 High energy phosphate compounds
23.6 An overview of biochemical energy production
23.7 The citric acid cycle
23.8 The electron transport chain
23.9 Oxidative phosphorgylation
23.10 ATP production for the common metabolic pathways
23.11 Non-ETC oxygen-consuming reactions
23.12 B-vitamins and the common metabolic pathways
23.1 Metabolism
Metabolism
 Sum total of all chemical reactions in a living
organism
 Source of energy for the functioning of the
human body
 Also needed for many of the cellular processes
such as protein synthesis, DNA replication, RNA
transcription, and membrane transport
Subtypes of Metabolic Reactions
 Catabolism: All metabolic reactions in which
large biochemical molecules are broken down
to smaller ones
 Usually energy is released in these reactions
 Example: Oxidation of glucose
 Anabolism: All metabolic reactions in which
small biochemical molecules are joined to form
larger ones
 Usually require energy
 Example: synthesis of proteins
anabolism
Metabolic Pathway
 Series of consecutive biochemical reactions
used to convert a starting material into an end
product
 There are two types of metabolic pathways:
 Linear
 Cyclic
 Major pathways for all forms of life are similar
23.2 Metabolism and cell structure
 Knowledge of the cell structure is essential for
understanding metabolism
 Prokaryotic cell:
 No nucleus and found only in bacteria
 Presence of a single circular DNA molecule near
the center of the cell called nucleoid
 Eukaryotic cell: Cell where the DNA is found in
a membrane-enclosed nucleus
 About 1000 times larger than bacterial cells
eukaryotic cell
A). A schematic representation of a mitochondrion,
showing key features of its internal structure.
Eukaryotic Cell Organelles and Their
Function
 Plasma membrane – Cellular boundary
 Cytoplasm: Water-based material of a
eukaryotic cell
 Mitochondrion: generates most of the energy
needed for a cell
 Lysosome: Contains hydrolytic enzymes
needed for cell rebuilding, repair, and
degradation
 Ribosome – Site for protein synthesis
 Nucleus- Site where DNA is found
Mitochondrion
 An organelle that is responsible for the
generation of most of the energy for a cell
 Outer membrane- Permeable to small
molecules
 50% lipid and 50% protein
 Inner membrane – Highly impermeable to most
substances
 20% lipid and 80% protein
 Folded to increase surface area
 Synthesis of ATP occurs here
  A phosphoryl group is derived from a Role of Other Nucleotide
23.3 Important nucleotide- phosphate ion when it becomes part of another
Triphosphates in Metabolism
containing compounds in molecule
 Uridine triphosphate (UTP)- involved in
metabolic pathway carbohydrate metabolism
 Guanosine triphosphate (GTP)- involved in
 The net energy produced in these reactions is protein and carbohydrate metabolism
Adenosine Phosphates (ATP, ADP, used for cellular reactions  Cytidine triphosphate (CTP)- involved in lipid
and AMP) metabolism

 Adenosine phosphates of interest: Flavin Adenine Dinucleotide (FAD)

 Adenosine monophosphate (AMP) – One  Coenzyme required in numerous metabolic
phosphate group redox reactions
 Structural component of RNA - Flavin subunit is the active form which
 Adenosine diphosposphate (ADP) Two gains H atoms when FAD is converted to
phosphate groups FADH2
 Key component of metabolic - Ribitol is a reduced form of the sugar
pathways ribose
 Adenosine triphosphate (ATP)- Three Nicotinamide Adenine Dinucleotide
phosphate groups (NAD)
 Key component of metabolic
pathways  Has coenzyme functions in metabolic
redox
 NAD+ is the oxidized form of NAD
 NADH is reduced form
 Typical cellular reaction in which NAD+
serves as the oxidizing agent is the
oxidation of a secondary alcohol to give a
ketone
 In cellular reactions, ATP functions as both a
source of a phosphate group and a source of
energy
 Example: Conversion of glucose to glucose-6-
phosphate

 FAD is the oxidized form

 FADH2 is the reduced form
 In enzyme reactions, FAD goes back and forth
from oxidized to reduced form
 Typical cellular reaction in which FAD serves as
oxidizing involves conversion of an alkane to
an alkene

Classification of Metabolic
Intermediate Compounds
 Metabolic intermediate compounds can be
classified into three groups based on their
functions
Coenzyme A
 Derivative of vitamin B panthothenic acid
 Active form of coenzyme A is the sulfhydryl
group (-SH group) in the ethanethiol subunit
of the coenzyme
 Acetyl-CoA- Formed when acetyl group
bonds to CoA-SH via a thioester bond
Coenzyme A Subunit Structures
23.4 Important carboxylate
ions in metabolic pathways
Carboxylate Ions (metabolic acids)
 Polyfunctional acids formed
intermediates of metabolic reactions
 There are 5 such acids that serve as
substrates for enzymes in metabolic
reactions:
- 3 succinic acid derivatives (C4 diacid)
 Fumarate, oxaloacetate,
malate
- 2 glutaric acid derivatives (C5 diacid)
 A-ketoglutarate and citrate
23.5 High energy phosphate
compounds
 Several phosphate-containing compounds
found in metabolic pathways are known as
high-energy compounds
 High-energy compounds: Have greater free
energy of hydrolysis than a typical
compound
- They contain at least one reactive bond
called strained bond
 Energy to break these bonds is less
than a normal bond
 More negative the free energy of
hydrolysis, greater the bond strain
 Typically the free-energy release is greater
than 6.0 kcal/mole (indicative of bond strain)
 Strained bonds are represented by the sign ~
(squiggle)
as
and
23.6 An overview of
biochemical energy
production
 Energy needed to run the human body is
obtained from food via a multistep process
involving several different catabolic
pathways
 There are four general stages in the
biochemical energy production process:
- Stage 1: Digestion
- Stage 2: Acetyl group formation
- Stage 3: Citric acid cycle
- Stage 4: Electron transport chain and
oxidative phosphorylation
 Each stage also involves numerous reactions
Stage 1: Digestion
 begins in the mouth (saliva contains starch-
digesting enzymes), continues in the
stomach (gastric juices), and is completed in
the small intestine
- Results in small molecules that can cross
intestinal membrane into the blood
stream
 End products which are absorbed and
transported to blood cells:
-glucose and monosaccharides from
carbohydrates
-Amino acids from proteins
-Fatty acids and glycerol from fats and oils
Stage 2: Acetyl group formation
 The small molecules from stage 1 are further
oxidized
 End product of these oxidations is acetyl CoA
and reduced coenzyme NADH
 This stage involves numerous reactions
which occur both in the cytosol as well as the
mitochondria of the cells
Stage 3: Citric acid cycle Reactions of the Citric Acid Cycle Step 4

 Takes place inside the mitochondria
 Acetyl group is oxidized to produce CO2 and
energy
 Some energy produced in this stage is lost in
the form of heat
-Most energy is trapped in reduced
coenzymes NADH and FADH2
 The carbon dioxide we exhale comes
primarily from this stage
Stage 4: Electron transport chain and
oxidative phosphorylation
 Takes place in mitochondria
 NADH and FADH2 are oxidized to release H
ions and electrons
- Needed for the production of ATP ,
primary energy carrier in metabolic
pathways
 O2 inhaled is converted into H2O in this
stage
23.7 The citric acid cycle
Citric Acid Cycle – An introduction
 Is the series of biochemical reactions in
which the acetyl portion of acetyl CoA is
oxidized to carbon dioxide and the reduced
coenzymes FADH2 and NADH are produced
 Also known as:
- Tricarboxylic acid cycle (TCA)- presence of
three carboxylate groups in citric acid
- Krebs cycle- Named after Hans Krebs who
elucidated this pathway
 Important reactions in the citric acid cycle
include:
- Reduction of NAD+ and FAD to produce
NADH and FADH2
- Decarboxylation of citric acid to produce
carbon dioxide
 Summary of citric acid cycle reactions:
 Step 1: Formation of Citrate.
 Step 2: Formation of Isocitrate
 Step 3: Oxidation of Isocitrate and Formation of
CO2.
- Involves oxidation- reduction as well as
decarboxylation
 Step 4: Oxidation of a-Ketoglutarate and
Formation of CO2. Step5
 Step 5: Thioester Bond Cleavage in Succinyl CoA
and Phosphorylation of GDP
 Step 6: Oxidation of Succinate.
 Step 7: Hydration of Fumarate
 Step 8: Oxidation of l-Malate to Regenerate
Oxaloacetate
Step 1
Step 6
Step 2

Step 7

Step 3

Step 8
Regulation of the Citric Acid Cycle - Two mobile electron carriers:
 Coenzyme Q and cytochrome c
 The rate at which the citric acid cycle
operates is controlled by the body’s need for Complex I: NADH–Coenzyme Q Reductase
ATP
 NADH, from the citric acid cycle, is the
- When ATP supply is high, ATP inhibits
source for the electrons that are processed
citrate synthase (step 1 of the cycle)
through complex I
- When ATP levels are low, ADP activates
 It contains more than 40 subunits, including
citrate synthase
the B-vitamin-containing flavin
 Similarly, ADP and NADH control isocitrate
mononucleotide (FMN) and several iron–
dehydrogenase
sulfur proteins (FeSP)
- NADH acts as an inhibitor
 net result of electron movement through
- ADP acts as an activator
complex I is the transfer of electrons from
NADH to coenzyme Q (CoQ)
- several intermediate carriers are involved
23.8 The Electron Transport
Chain Complex IV: Cytochrome c Oxidase

The electron transport chain- An  contains 13 subunits, including two

introduction
 Series of biochemical reactions in which
intermediate carriers aid the transfer of
electrons and hydrogen ions from NADH and
FADH2
- Ultimately react with molecular oxygen to
give H2O
 Lost energy is used to synthesize ATP in
oxidative phosphorylation
Enzyme and Electron Carriers for ETC
 Located along inner mitochondrial
membrane
 Organized into four distinct protein
complexes and two mobile carriers
- Protein complexes tightly bound to
membrane:
 Complex I: NADH–coenzyme Q
reductase
 Complex II: Succinate–coenzyme Q
reductase
 Complex III: Coenzyme Q–
cytochrome c reductase
 Complex IV: Cytochrome c oxidase
Complex III: Coenzyme Q–Cytochrome c
Reductase
Complex II: Succinate–coenzyme Q
reductase
 smaller than complex I
 contains only four subunits, including two
FeSPs
 succinate is converted to fumarate via this
complex
 This complex processes FADH2
- CoQ is the final recipient of the electrons
from FADH2
cytochromes
 The electron movement flows from cyt c to cyt
a to cyt a3.
 In the final step of electron transfer, the
electrons from cyt a3 and hydrogen ions from
cellular solution combine with oxygen (O2) to
form water.
 contains 11 different subunits.
 Several FeSP proteins and cytochromes are
electron carriers in this complex  It is estimated that 95% of the oxygen used by
- cytochrome is a heme-containing protein cells serves as the final electron acceptor for
in which reversible oxidation and the ETC
reduction of an iron atom occur.
 Various cytochromes, abbreviated cyt a, cyt b,
cyt c, and so on, differ from each other in
- their protein constituents,
- the manner in which the heme is bound to
the protein, and
- attachments to the heme ring.

23.9 Oxidative
phosphorylation
Oxidative phosphorylation – An introduction
 Oxidative phosphorylation: Process by which
ATP is synthesized from ADP using the energy
released in the electron transport chain
- Can be occupied reactions
 Coupled reactions: Pairs od biochemical
reactions that occur concurrently in which
energy released by one reaction is used in the
other reaction
- Examples: Oxidative phosphorylation and
the oxidation reactions of the electron
transport chain
 Coupling of ATP synthesis with the reactions
of the ETC is related to the movement of
protons (H+ ions) across the inner
mitochondrial membrane
 Complexes I,III, AND IV of ETC chain have a
second function
- Serve as “proton pumps” transferring
protons from the matrix side of the inner
mitochondrial membrane to the
intermembrane space
 For every two electrons passed through ETC,
four protons cross the inner mitochondrial
membrane through complex I, four through
complex III, and two more though complex
IV
 This proton flow causes a buildup of H+ in
the intermembrane space
 This high concentration of protons passing
through ATP synthase becomes the basis for
the ATP synthesis
A second function for protein complexes I, III, and IV
23.11 Non-ETC oxygen-
consuming reactions
Reactive Oxygen Species (ROS)
23.10 ATP production for the
common metabolic pathways
ATP formation
 For each mole of NADH oxidized in the ETC,
2.5 moles of ATP are formed
 For each mole of FADH2 oxidized in the ETC,
only 1.5 moles of ATP are formed
 For each mole of GTP hydrolyzed, one mole
of ATP is formed
 Ten molecules of ATP are produced for each
acetyl CoA catabolized
 ROS formed quickly converted to non-toxic
species
 About 5% of ROS escape destruction by
superoxide dismutase and catalase enzymes
 Antioxidant molecules present in the body
help trap ROS species
- Vitamin E
- Vitamin C
- Glutathion
- Beta-carotene
 Major family of antioxidant phytochemicals
are flavonoids
23.12 B-vitamins and the
common metabolic pathways
 Structurally modified B vitamins function as
coenzymes in metabolic pathways
 >90% of inhaled oxygen via respiration is
 four vitamins have involvement in these
consumed during oxidative phosphorylation
metabolic reactions:
 Remaining O2 is converted to several highly
reactive oxygen species (ROS) within the - Niacin—as NAD+ and NADH
- Riboflavin—as FAD, FADH2, and
body, which include:
FMN
- Hydrogen peroxide (H2O2)
- Thiamin—as TPP
- Superoxide ion (O2)
- Hydroxyl radical (OH) - Pantothenic acid—as CoA
 Superoxide ion and hydroxyl  In the absence of these B vitamins, the body
would be unable to utilize carbohydrates,
radicals have an unpaired electron
 Can also be formed due to external proteins, and fats as energy source
influences such as polluted air, cigarette
smoke, and radiation exposure
 Are both beneficial as well as problematic
within the body
 Example: White blood cells produce a
significant amount of superoxide free
radicals via the following reaction to destroy
the invading bacteria and viruses