CHAPTER

2
Chemistry,
Biochemistry, and Cell
Physiology
Part 2

PowerPoint® Lecture Slides prepared by

Stephen Gehnrich, Salisbury University

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 Biochemistry

Metabolic pathways
 Series of reactions that convert subtrates to
products
 Catalyzed by enzymes
 Synthesis (anabolic)
 Degradative (catabolic)
 Amphibolic ( both anabolic and catabolic; Krebs
Cycle)
 Metabolic pathways are linked by intermediates
 Metabolism – sum of metabolic pathways for the
synthesis and breakdown of molecules.

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 Enzymes

Catalysts that accelerate chemical reactions

 Enzymes have three properties
1. Active at low concentrations
2. Increase the rate of reactions but are not altered
3. Do not change the products
 Most are made of proteins
 Some are made of RNA (ribozymes)

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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
 Cofactors
 Nonprotein components of
enzymes
 Many are loosely associated
with enzymes
 Prosthetic group – cofactor
covalently bonded into the
enzyme
 Coenzymes – organic
cofactors usually derived
from vitamins; transfer
electrons between enzymes
 Inorganic ion cofactors –
mostly metallic ions: copper,
iron, magnesium, zinc
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 Reducing Energy
 Reducing equivalents – electrons
bound to a carrier
 Example: NADH, NADPH,
FADH2, FMNH2
 Oxidoreductases – enzymes that
transfer reducing equivalents
between reduced (energy-rich) and
oxidized (energy-poor) molecules
 Example: lactate dehydrogenase
 NAD+ + lactate  NADH + H+
+ pyruvate
 Redox status – reducing energy
within a cell
 reduced form/oxidized form
 Example: [NADH/NAD+]
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 Reaction Acceleration
 Enzymes accelerate reactions
by reducing activation
energy (EA)
 Same substrate and product
as uncatalyzed reaction
 Enzyme catalyzed reaction
has a different intermediate
at the transition state
 S + E  ES  ES* 
EP*  EP  E + P

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 Environmental Effects
Enzyme activity is affected by
concentration, temperature,
pH, salinity, and hydrostatic
pressure
Enzymes are affected in
different ways
 Changes in weak bonds
alter three-dimensional
structure
 Changes in ionization
state of amino acids
within the active site
 Changes in the ability of
the enzyme to undergo
structural changes
necessary for catalysis
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 Regulation of Enzyme Activity

 Competitive inhibitors
 Block the active site
 Allosteric regulators
 Alter the three-
dimensional shape of
the enzyme
 Covalent modification
 Phosphorylation alters
enzyme activity

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 Biomolecules

Four main types

 Proteins
 Carbohydrates
 Lipids
 Nucleic acids

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 Proteins

 Contribute to cell structure and function

 Mediate all cellular processes
 Enzymes
 Have complex three-dimensional structure
 Protein structure is coded in DNA

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 Amino Acids
 Proteins are polymers of
amino acids
 Amino acids – amino group (–
NH2) and carboxylic acid
group (–COOH)
 Termed a-amino acids
because –NH2 and –COOH
are located on the first (a)
carbon
 Distinguished by side groups
(R)
 Can be nonpolar
(hydrophobic), polar-
uncharged (hydrophilic) and
polar-charged (hydrophilic)
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 Primary Structure

Linear sequence of amino acids joined by covalent

bond between the carboxyl and amino group
 Peptide bond

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 Secondary Structure

 Localized folding
 Linked by hydrogen bonds
 a-helix
 b-sheet

Figure 2.21
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 Tertiary Structure

Covalent bonds
 Disulfide bonds
Weak bonds
 van der Waals forces
 Ionic bonds
 Hydrogen bonds

Figure 2.22
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 Quaternary Structure
Protein made of multiple
polypeptide chains
 Dimer – two subunits
 Homodimer – identical proteins
 Heterodimer – different
proteins
 Trimer – three subunits
 Tetramer – four subunits
 Ex. Hemoglobin has four
polypeptides; two alpha and
two beta subunits

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 Molecular Chaperones

Proteins function properly only when folded into

correct three-dimensional shape
 Some proteins fold spontaneously
 Some are helped by molecular chaperones
 Force protein into conformation that allows weak
bonds to form
 For example, heat shock proteins (Hsp 70)

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 Carbohydrates

 “Hydrates of carbon”
 Many hydroxyl (–OH) groups
 Glucose is the most common carbohydrate in
animal diets
 Energy metabolism
 Biosynthesis – precursor to many other
carbohydrates

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 Monosaccharides

Figure 2.23
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 Disaccharides

 Two monosaccharides
connected by a
covalent bond
 Bond is broken during
metabolism

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 Carbohydrates + Other Macromolecules

Glycosylation – addition of carbohydrates to other

macromolecules
Alters function of the macromolecule
For example, glycolipids, glycoproteins
 Both are typically found in plasma membranes and
extracellular fluid

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 Complex Carbohydrates

 Polysaccharides
 Long chain of
monosaccharides
 Energy storage
 Example: glycogen,
starch
 Structural molecules
 chitin, hyaluronate,
cellulose (in plants)

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 Glycogen Metabolism
Glycogen synthesis (glycogenesis)
Glycogen breakdown (glycogenolysis)

Figure 2.26
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 Glucose Metabolism
Glucose synthesis
(gluconeogenesis)
 Glycine, serine, alanine,
lactate as precursors
 Fatty acids can not be used
as substrates by animal
cells
 2 pyruvate + 4ATP +
2GTP + 2NADH + 4H2O
 glucose + 4ADP +
2GDP + 6Pi + 2NAD+ +
2H+
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 Glucose Metabolism
Glucose breakdown (glycolysis)
 Produces reducing equivalents
 Releases energy
 Glucose + 2ADP + 2NAD+ 
2ATP + 2 pyruvate + 2NADH +
2H+
 Takes place in cytoplasm
 Does not require oxygen
 Produces intermediates for
synthesis of various molecules
 Carbohydrates, nucleic acids,
amino acids, and fatty acids

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 Oxidation of Pyruvate in the Presence of O2
Glycolysis
 Converts carbohydrates
to pyruvate within the
cytoplasm
 Lactate and amino
acids can also be
converted to pyruvate
 Pyruvate is carried into
the mitochondria
Pyruvate dehydrogenase
(PDH)
 Pyruvate is oxidized by
PDH to form acetyl
CoA + NADH

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 Oxidation of NADH in the Presence of O2
Glycerol phosphate Shuttle Malate-aspartate Shuttle
Cytosolic NADH reduces Malate crosses to the
dihydroxyacetone phosphate to mitochondrial matrix and
glycerol phosphate crosses to the
reduces NAD+ to form
mitochondrial matrix which
reduces FAD to FADH2 forms 2 NADH which forms 3ATPs
ATPs per molecule of FADH2 per molecule of NADH

Figure 2.29
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 Oxidation of NADH in the Absence of O2
(hypoxia- and anoxia tolerant animals)
 Dormant, high glycogen stored
 NADH cannot be used by
mitochondria when oxygen is not
present
 NADH is oxidized in the
cytoplasm
 pyruvate + NADH + H+  lactate +
NAD+
 Catalyzed by the enzyme lactate
dehydrogenase (LDH)
 Other anaerobic pathways form less
toxic end products and more ATP
than lactate (2 ATP); tauropine,
nopaline, ethanol production
 For example, succinate (4 ATP)
and proprionate (6 ATP)
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 Lipids

 All are hydrophobic (do not dissolve in water)

 Carbon backbone
 Linear – aliphatic
 Ring – aromatic
 Examples: fatty acids, triglycerides, phospholipids,
steroids
 Lipids are used for energy metabolism, cell
structure, and signaling

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 Fatty Acids

 Chain of carbon atoms

ending with a carboxyl
group
 Usually an even number of
carbons
 Saturated
 No double bonds between
carbons
 Unsaturated
 One or more double bonds
between carbons

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 Fatty Acid Oxidation (b-Oxidation)
Fatty acids are synthesized from
Acetyl CoA
 Catalyzed by the enzyme
fatty acid synthase (FAS)

Breakdown of fatty acids

 b-oxidation
 Takes place in
mitochondria
 Results in formation
of Acetyl CoA
 Acetyl CoA is
oxidized

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 Ketones
 Some tissues cannot
metabolize fatty acids, but
they can metabolize ketones:
acetone, acetoacetate, β-
hydroxybutyrate
 For example, vertebrate
brain, shark muscle
 Ketogenesis
 Fatty acids (acetyl CoA)
are converted to ketones
 Ketolysis
 Ketones are broken down
to acetyl CoA

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 Triglycerides
 Fatty acids esterified to a
glycerol backbone
 For example, mono-,di-, tri-
acylglycerol
 Fatty acids are stored as
triglycerides
 Long-term storage of fatty
acids
 Primary storage tissues:
adipose and liver
(vertebrates), hepatopancreas
(invertebrates)
 Lipases break the bond between
fatty acid and glycerol backbone
(lipolysis)
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 Triglyceride Synthesis or Lipogenesis

Figure 2.35
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 Phospholipids

 Dominate biological
membranes
 Two classes of phospholipids
in animal cells:
 Phosphoglycerides
 Constructed from
diacylglycerol
 Polar group on third carbon
 Sphingolipids
 Sphingosine backbone
 Phospholipids are broken
down by phospholipases
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 Steroids
 Four hydrocarbon rings
 Synthesis involves
many intermediates

Figure 2.37
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 Mitochondrial (Oxidative) Metabolism
Energy-yielding reactions that require oxygen
 Enzymes convert nutrients into metabolites
 Metabolites enter mitochondria
 Many metabolites are converted to acetyl
CoA
 Acetyl CoA enters the tricarboxylic acid
cycle (TCA cycle)
 Acetyl CoA is oxidized to form reducing
equivalents
 Reducing equivalents are oxidized to
release energy
 GTP (ATP) synthesis by substrate-level
phosphorylation

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 Formation of acetyl CoA

Figure 2.38
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 Oxidative Metabolism

Acetyl CoA

Tricarboxylic acid (TCA) cycle
acetyl CoA  CO2 + reducing equivalent (NADH and
FADH2) and GTP

Electron transport system (ETS)
reducing equivalents are oxidized to release energy

Oxidative phosphorylation
ATP synthesis (phosphorylation)

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 Tricarboxylic Acid (TCA) Cycle

 Generates reducing equivalents within the

mitochondria
 Acetyl CoA + 3NAD+ + GDP + Pi + FAD  2CO2 +
3NADH + FADH2 + GTP
 Amphibolic pathway
 Some intermediates are broken down (catabolic)
 Some intermediates are used for syntheses (anabolic)

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 Electron Transport System (ETS)
Electrons from NADH and
FADH2 are transferred to the
ETS
 Found within the inner
mitochondrial membrane
 Composed of four
multisubunit proteins
(complexes I, II, III, IV)
and two electron carriers
(ubiquinone and
cytochrome c)
 Oxidation: 4e– + 4H+ +
O2  2H2O
 Generates a proton
gradient, heat, water, and
reactive oxygen species
(ROS)
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 ATP Synthesis and Heat Production
 Phosphorylation: ADP + Pi  ATP
 Proton motive force (Dp)
 Electrochemical gradient: pH gradient and the
membrane potential (DY)
 F1F0ATPase uses energy in Dp to produce ATP
 There is no physical linkage between oxidation
(ETS) and phosphorylation (F1F0ATPase)
 Two processes are functionally coupled through Dp
 Uncoupling proteins (UCPs) in inner mitochondrial
membrane of brown adipose tissues of mammals
(hibernators, newborns) which facilitate movement
of protons and produce heat instead of ATP.
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 Phosphocreatine

 Alternative high-energy phosphate compound

 Creatine + ATP  ADP + phosphocreatine
 Creatine phosphokinase (CPK)
 Reaction is reversible so phosphocreatine can be
used to produce ATP when levels are low
 Maintains ATP level to sustain muscle contraction
at longer duration
 Phosphocreatine shuttle as pathway to improve
efficiency of energy transfer within the cell: faster
rate of diffusion the smaller molecules creatine and
phosphocreatine compared to adenylates
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 Phosphocreatine

Figure 2.41
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 Integration of Metabolic Pathways

 Fluctuations in nutrient availability, energy

demand, and environmental conditions
 Reciprocal regulation avoids simultaneous
synthesis and degradation (futile cycles)
 Use of appropriate metabolic “fuel”
 Carbohydrate vs. lipid
 Energetic intermediates regulate balance between
anabolism and catabolism

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 Reciprocal Regulation: Balance bet.
Anabolism and Catabolism
 High concentrations of acetyl
CoA, NADH and ATP :
inhibit glycolysis and
stimulate gluconeogenesis
 Cells separate anabolism and
catabolism by using tissue
specialization: muscles have
enzymes for ketolysis but not
for ketogenesis but liver has.
 Liver and adipose tissues give
priority for the whole animal
metabolic balance rather than
their own needs.

Figure 2.42
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