BIOCHEMISTRY

• Flavin Adenine Dinucleotide (FAD,

BIOCHEMICAL ENERGY FADH2)
PRODUCTION • Nicotinamide Adenine Dinucleotide
(NAD, NADH)
METABOLISM
• Coenzyme A (CoA–SH)
Is the sum of all the biochemical
reactions that take place in a living
ADENOSINE PHOSPHATES (ATP, ADP, AND
organism.
AMP)
Energy needed to run human body
• 7ADP and ATP differ structurally
is obtained from food.
from AMP only in the number of
Multi-step process that involves
phosphate groups present. Block
several different catabolic pathways.
structural diagrams for these three
adenosine phosphates follow.
2 SUBTYPES
1. Catabolism: is all metabolic • A phosphoryl group is the
reactions in which large functional group derived from a
biochemical molecules are broken phosphate ion that is part of
down to smaller ones another molecule.
2. Anabolism: is all metabolic • When two phosphate groups react
reactions in which small with one another, a water molecule
biochemical molecules are joined is produced hence the use of the
together to form larger ones. word anhydride in describing the
*The processes of Catabolism catabolism chemical bonds present between
and anabolism are opposite in nature. The phosphoryl groups in ATP and ADP.
first usually produces energy, and the
second usually consumes energy.

FLAVIN ADENINE DINUCLEOTIDE (FAD,

FADH2)
• Flavin adenine dinucleotide (FAD) is
a coenzyme required in numerous
metabolic redox reactions.
METABOLIC PATHWAY • The active portion of FAD in
A metabolic pathway is a series of metabolic redox reactions is the
consecutive biochemical reactions used to flavin subunit of the molecule.
convert a starting material into an end
product. Such pathways may be linear, in
which a series of reactions generates a final
product, or cyclic, in which a series of NICOTINAMIDE ADENINE DINUCLEOTIDE
reactions regenerates the first reactant (NAD, NADH)
• Both have coenzyme functions in
IMPORTANT INTERMEDIATE metabolic redox pathways, both
COMPOUNDS IN METABOLIC PATHWAYS have a B vitamin as a structural
• Adenosine Phosphates (ATP, ADP, component, and both can be
and AMP) represented structurally by using a
 three-subunit or a six-subunit Stage 2: Acetyl group formation,
formulation. In the case of NAD, the Stage 3: Citric acid cycle
B vitamin present is nicotinamide. Stage 4: electron transport chain
• The active portion of NAD in and oxidative phosphorylation
metabolic redox reactions is the
nicotinamide subunit of the STAGE 1. DIGESTION
molecule. The nicotinamide is Begins in mouth (saliva contains
reduced, converting the NAD to starch digesting enzymes), continues in the
NADH, a molecule with one stomach (gastric juice), completed in small
additional hydrogen atom and two intestine:
additional electrons. Thus, NAD is • Results in small molecules that can
the oxidized form of the molecule, cross intestinal membrane into the
and NADH is the reduced form blood
End Products of digestion:
COENZYME A (COA–SH) • Glucose and monosaccharides
• The active portion of coenzyme A is from carbohydrates
the sulfhydryl. For this reason, the • Amino acids from proteins
abbreviation CoA–SH is used for • Fatty acids and glycerol from fats
coenzyme A. and oils
• An acetyl group is the portion of an The digestion products are absorbed into
acetic acid molecule (CH3–COOH) the blood and transported to body’s cells
that remains after the —OH group STAGE 2. ACETYL GROUP FORMATION
is removed from the carboxyl The small molecules from Stage 1
carbon atom. An acetyl group are further oxidized. End product of these
bonds to CoA–SH through a oxidations is acetyl CoA. Involves
thioester bond (Section 16.17) to numerous reactions:
give acetyl CoA • Reactions occur both in cytosol
(glucose metabolism) as well as
CLASSIFICATION OF METABOLIC mitochondria (fatty acid
INTERMEDIATE COMPOUNDS metabolism) of the cells.
The metabolic intermediate STAGE 3. CITRIC ACID CYCLE
compounds considered in this section can • Takes place in inside the
be classified into three groups based on mitochondria
function. The classifications are: • First intermediate of the cycle is
1. Intermediates for the storage of citric acid – therefore designated as
energy and transfer of phosphate Citric acid cycle
groups • In this stage acetyl group is oxidized
2. Intermediates for the transfer of to produce CO2 and energy
electrons in metabolic redox • The carbon oxide we exhale comes
reactions primarily from this stage
3. Intermediates for the transfer of • Most energy is trapped in reduced
acetyl groups coenzymes NADH and FADH2
• Some energy produced in this stage
THERE ARE FOUR GENERAL STAGES IN THE is lost in the form of heat
BIOCHEMICAL ENERGY PRODUCTION STAGE 4. ELECTRON TRANSPORT CHAIN
PROCESS: AND OXIDATIVE PHOSPHORYLATION
Stage 1: Digestion • Takes place in mitochondria
 • NADH and FADH2 are oxidized to Summary of citric acid cycle reactions:
release H+ and electrons Acetyl CoA + 3NAD+ + FAD + GDP + Pi +
• H+ are transported to the inter- 2H2O -> 2CO2 + CoA-SH + 3NADH + 2H+ +
membrane space in mitochondria FADH2 + GTP
• Electrons are transferred to O2 and
O2 is reduced to H2O
• H+ ions reenter the mitochondrial
matrix and drive ATP-synthase
reaction to produce ATP
• ATP is the primary energy carrier in
metabolic pathways

CITRIC ACID CYCLE REACTIONS OF THE CITRIC ACID CYCLE

A series of biochemical reactions in Step 1: Formation of Citrate
which the acetyl portion of acetyl CoA is Step 2: Formation of Isocitrate
oxidized to carbon dioxide and the reduced Step 3: Oxidation of Isocitrate and
coenzymes FADH2 and NADH are Formation of CO2: involves oxidation–
produced. reduction as well as decarboxylation
Also known as tricarboxylic acid Step 4: Oxidation of Alpha-Ketoglutarate
cycle (TCA) or Krebs cycle: and Formation of CO2
• Citric acid is a tricarboxylic acid – Step 5: Thioester bond cleavage in Succinyl
TCA cycle CoA and Phosphorylation of GDP
• Named after Hans Krebs who Step 6: Oxidation of Succinate
elucidated this pathway Step 7: Hydration of Fumarate
Two important types of reactions: Step 8: Oxidation of L-Malate to
• Oxidation of NAD+ and FAD to Regenerate Oxaloacetate
produce NADH and FADH2
• Decarboxylation of citric acid to
produce carbon dioxide
• The citric acid cycle also produces 2
ATP by substrate level
phosphorylation from GTP
 molecules per every molecule of
Regulation of the Citric Acid Cycle: NADH processed through ETC
• The rate at which the citric acid • The enzymes and electron carriers
cycle operates is controlled by ATP needed for the ETC are located
and NADH levels along inner mitochondrial
• When ATP supply is high, ATP membrane
inhibits citrate synthase (Step 1 of • They are organized into four
Citric acid cycle) distinct protein complexes and two
• When ATP levels are low ADP, ADP mobile carriers
activates citrate synthase
• Similarly, ADP and NADH control 4 PROTEIN COMPLEX
isocitrate dehydrogenase: • Complex 1: NADH-coenzyme Q
➢ NADH acts as an inhibitor reductase
➢ ADP as an activator. • Complex II: Succinate-coenzyme Q
reductase
ELECTRON CHAIN TRANSPORT • Complex III: Coenzyme Q -
• The electron transport chain (ETC) cytochrome C reductase
facilitates the passage of electrons • Complex IV: Cytochrome C oxidase
trapped in FADH2 and NADH during • Two mobile electron carrier :
citric cycle Coenzyme Q and Cytochrome
• ETC is a series of biochemical
reactions in which intermediate COMPLEX 1: NADH-COENZYME Q
carriers (protein and non-protein) REDUCTASE
aid the transfer of electrons and • NADH from citric acid cycle is the
hydrogen ions from NADH and source of electrons for this complex
FADH2 • It contains >40 subunits including
• The ultimately receiver of electrons flavin mononucleotide (FMN) and
is molecular oxygen several iron-sulfur protein clusters
• The electron transport (respiratory (FeSP)
chain) gets its name from the fact • Net result: Facilitates transfer of
electrons are transported to electrons from NADH to coenzyme
oxygen absorbed via respiration Q
• The overall ETC reaction: 2 H+ + 2e- • Several intermediate reactions are
+ 1/2 O2 H2O + energy involved in this electron transfer
• Energy is used to synthesize ATP in COMPLEX II: SUCCINATE-COENZYME Q
oxidative phosphorylation REDUCTASE
• Note that 2 hydrogen ions, 2 • Smaller than complex I
electrons, and one half-oxygen • Contains only four subunits
molecule react to form the product including two iron-sulfur protein
water clusters (FeSP)
• This relatively straight forward • Succinate is converted to fumarate
reaction requires eight or more by this complex
steps • In the process it generates FADH2
• The reaction releases energy CoQ is the final recipient of the
(exothermic reaction) electrons from FADH2
• The energy released is coupled with
the formation of three ATP
COMPLEX III: COENZYME Q –
CYTOCHROME C REDUCTASE
• Complex III contains 11 different
subunits
• Several iron-sulfur proteins and
cytochromes are electron carriers
in this complex
• Cytochrome is a heme iron protein
in which reversible oxidation of an
iron atom occurs
• Various cytochromes, e.g., cyt a,
cyt b, cyt c, differ from each other
by:
➢ Their protein constituents
➢ The manner in which the
heme is bonded to the
protein
➢ Attachments to the heme
ring
COMPLEX IV: CYTOCHROME C OXIDASE
• Contains 13 subunits including two
cytochromes
• The electrons flow from cyt c to cyt
a to cyt a3
• In the final stage of electron
transfer, the electrons from cyt a3,
and hydrogen ion (H+) combine
with oxygen (O2) to form water
• O2 + 4H+ + 4e- 2 H2O
• It is estimated that 95 % of the
oxygen used by cells serves as the
final electron acceptor for the ETC