10/26/2021

Chem413
Biochemistry
Part 1: Introduction to Biochemistry (1/2) 1

1. What is Biochemistry?
“Organic chemistry is the chemistry of carbon compounds. Biochemistry is
the study of carbon compounds that crawl.”

Mike Adams (University of Georgia)

 Central questions in biochemistry:

• What are living organisms made of?
• How do organisms acquire and use
energy?
• How does an organism maintain its
identity across generations?

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1.1. Properties of Living Matter

 Biochemistry can be defined as the chemistry of living matter.

 Living matter is characterized by:

• a high degree of complexity and organization
• the extraction, transformation, and systematic use of energy to
create and maintain structures and to do work
• the interactions of individual components being dynamic and
coordinated
• the ability to sense and respond to changes in surroundings
• a capacity for fairly precise self-replication while allowing enough
change for evolution

1.1. Properties of Living Matter

 Living matter is complex and well organized.

• Microscopic complexity and organization are apparent in

this colorized image of a thin section of several secretory
cells from the pancreas, viewed with the electron
microscope. 4

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1.1. Properties of Living Matter

 Living organisms must intake and transform nutrients into energy.

 Living organisms must accurately

reproduce.

1.1. Properties of Living Matter

 The scale of life:

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1.2. Classification of Living Matter

 Three distinct domains of life are defined by cellular and molecular
differences that evolved over time.

1.2. Classification of Living Matter

 Phylogenetic relationships are often illustrated
by a “family tree” of this type. The basis for
this tree is the similarity in nucleotide
sequences of the ribosomal RNAs of each
group; the more similar the sequences, the
closer the location of the branches, with the
distance between branches representing the
degree of difference between two sequences.

 Phylogenetic trees can also be constructed from similarities across species of the amino
acid sequences of a single protein. For example, sequences of the protein GroEL (a
bacterial protein that assists in protein folding) can be used to construct such trees.
 A “consensus” tree, which uses several comparisons such as these to derive the best
estimates of evolutionary relatedness among a group of organisms, can also be
established and would be a more accurate means for classification of life.
 Genomic sequences from a wide range of bacteria, archaea, and eukaryotes also are
consistent with a two-domain model in which eukaryotes are subsumed under the
Archaea domain. As more genomes are sequenced, one model may emerge as the clear
best fit for the data.
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1.2. Classification of Living Matter

 Six kingdoms of life can be defined by organismal, cellular, and molecular
differences.

Six Kingdoms Cellular Organization

• Archaea Unicellular prokaryote
• Bacteria Unicellular prokaryote
• Protista Unicellular eukaryote
• Fungi Uni- or Multicellular eukaryote
• Plantae Multicellular eukaryote
• Animalia Multicellular eukaryote

1.3. Cells as the Universal Building Blocks of Life

 Living organisms are made of cells.

 The simplest living organisms are unicellular (single-celled).
 Larger organisms are multicellular (many-celled), with different functions
for different cells.
 Cells have some common features but can contain unique components
for different organisms.

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1.3.1. Similarities Exist Between All Cells

 All cells have a nucleus or nucleoid containing their DNA, a plasma membrane, and
cytoplasm. The cytosol is defined as that portion of the cytoplasm that remains in the
supernatant after gentle breakage of the plasma membrane and centrifugation of the
resulting extract at 150,000 g for 1 hour. Eukaryotic cells contain a variety of membrane-
bounded organelles (including mitochondria, chloroplasts) and large particles (ribosomes,
for example), which are sedimented by this centrifugation and can be recovered from the
pellet.

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1.3.2. Prokaryotic and Eukaryotic Cells

 Bacterial and archaeal cells are prokaryotic.

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• Escherichia coli

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1.3.2. Prokaryotic and Eukaryotic Cells

 Composition and function of some structures in bacterial cells.
Structure Composition Function
Cell wall Carbohydrate + protein Mechanical support
Cell membrane Lipid + protein Permeability barrier
Nucleoid DNA + protein Genetic information
Ribosomes RNA + protein Protein synthesis
Pili Protein Adhesion, conjugation
Flagella Protein Motility
Cytoplasm Aqueous solution Site of metabolism

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2D 3D

1.3.2. Prokaryotic and Eukaryotic Cells

 Eukaryotic cells are more complex than prokaryotic cells.

• Have membrane-bound nucleus by definition:

– protection for DNA; site of DNA metabolism
– selective import and export via nuclear membrane pores

• Have membrane-enclosed organelles:

– mitochondria for energy in animals, plants, and fungi
– chloroplasts for energy in plant
– lysosomes for digestion of un-needed molecules

• Compartmental segregation of energy-yielding and energy-consuming

reactions helps cells to maintain homeostasis and stay away from
equilibrium.

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1.3.2. Prokaryotic and Eukaryotic Cells

 Animal cells are eukaryotic and range range from 5 to 30 m.

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1.3.2. Prokaryotic and Eukaryotic Cells

 Plant cells are eukaryotic and range range from 10 to 100 m.

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1.3.2. Prokaryotic and Eukaryotic Cells

 There are similarities and differences between animal and plant cells.

Plant Both Animal

Chloroplast
Membrane
Vacuole Nucleus and Nucleolus Lysosome
Mitochondria
Glyoxysome Rough and Smooth ER Peroxisomes
Ribosomes
Plasmodesma Golgi
Cytoskeleton
Cell wall

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1.3.3. Cytoplasm and Cytoskeleton

 Cytoplasm is a highly viscous solution where many reactions take place.

Cytoplasm is the total content within the cell membrane.

 Cytoskeleton consists of microtubules, actin filaments, and intermediate

filaments.
• cellular shape and division
• intracellular organization
• intracellular transport paths
• cellular mobility

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1.3.3. Cytoplasm and Cytoskeleton

 Cytosolsol is very crowded. Cytosol is the fluid contained in the cytoplasm.

• Detail from E. coli illustration.

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1.3.3. Cytoplasm and Cytoskeleton

 The cytoskeleton maintains cellular organization.
 The three types of cytoskeletal
filaments: actin filaments,
microtubules, and intermediate
filaments.
 Cellular structures can be labeled
with an antibody (that recognizes a
characteristic protein) covalently
attached to a fluorescent
compound. The stained structures
are visible when the cell is viewed
with a fluorescence microscope.
 In this cultured fibroblast cell,
bundles of actin filaments are
stained red; microtubules, radiating
from the cell center, are stained
green; and chromosomes (in the
nucleus) are stained blue. 20

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1.4. Biochemistry is the Chemistry of Living Matter

 The basis of all life is the chemical reactions that take place within the
cell.

 Chemistry allows for:

• a high degree of complexity and organization
• the extraction, transformation, and systematic use of energy to
create and maintain structures and to do work
• the interactions of individual components to be dynamic and
coordinated
• the ability to sense and respond to changes in surrounding
• a capacity for fairly precise self-replication while allowing enough
change for evolution

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1.4.1. The Molecular Hierarchy of Structure

 Structural hierarchy in the molecular organization of cells. The organelles and other
relatively large components of cells are composed of supramolecular complexes, which in
turn are composed of smaller macromolecules and even smaller molecular subunits. For
example, the nucleus of this plant cell contains chromatin, a supramolecular complex that
consists of DNA and basic proteins (histones). DNA is made up of simple monomeric
subunits (nucleotides), as are proteins (amino acids).

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1.4.2. Carbon is Central in Biochemistry

 Carbon bonding is very versatile. Carbon can form covalent single, double,
and triple bonds, particularly with other carbon atoms. Triple bonds are
rare in biomolecules.

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1.4.3. 30 Elements Essential for Life

 Other than carbon, elements H, O, N, P, and S are also common.
 Metal ions (e.g., K+, Na+, Ca2+, Mg2+, Zn2+, Fe2+) play important roles in
metabolism.

• Elements essential to animal life and health. Bulk elements (shaded orange) are structural components
of cells and tissues and are required in the diet in gram quantities daily. For trace elements (shaded
bright yellow), the requirements are much smaller: for humans, a few milligrams per day of Fe, Cu, and
Zn, even less of the others. The elemental requirements for plants and microorganisms are similar to
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those shown here; the ways in which they acquire these elements vary.

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1.4.4. Common Functional Groups of Biological Molecules

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1.4.4. Common Functional Groups of Biological Molecules

 Several common functional groups may exist in a single biomolecule.
Acetyl-coenzyme A (often abbreviated as acetyl-CoA) is a carrier of acetyl
groups in some enzymatic reactions. Several of these functional groups
can exist in protonated or unprotonated forms, depending on the pH.

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1.4.5. The ABCs of Life

 The organic compounds from which most cellular materials are constructed
are given below. These are the ‘’ABCs‘’ of biochemistry.

 Shown here are:

• (a) six of the 20 amino
acids from which all
proteins are built (the side
chains are shaded pink)

• (b) the five nitrogenous

bases, two five-carbon
sugars, and phosphate ion
from which all nucleic acids
are built
• (c) five components of
membrane lipids
• (d) D-glucose, the simple
sugar from which most
carbohydrates are derived
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1.4.6. The Biological Function of Molecules Strongly Depends

on Their Stereochemistry

 Stereoisomers
• have different physical properties

 Geometric isomers (cis vs. trans)

• have different physical and chemical properties

 Enantiomers (mirror images)

• have identical physical properties (except with regard to
polarized light) and react identically with achiral reagents

 Diastereomers
• have different physical and chemical properties

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1.4.6. The Biological Function of Molecules Strongly Depends

on Their Stereochemistry
 Geometric isomerism and biological function. In the vertebrate retina,
the initial event in light detection is the absorption of visible light by 11-
cis-retinal. The energy of the absorbed light (about 250 kJ/mol) converts
11-cis-retinal to all-trans-retinal, triggering electrical changes in the
retinal cell that lead to a nerve impulse.

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1.4.6. The Biological Function of Molecules Strongly Depends

on Their Stereochemistry
 Stereoisomers have different effects in humans. Aspartame, the artificial
sweetener sold under the trade name NutraSweet, is easily distinguishable
by taste receptors from its bitter tasting stereoisomer, although the two
differ only in the configuration at one of the two chiral carbon atoms.

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1.4.7. Interations Between Biomolecules are Specific

 Macromolecules fold into 3D structures with unique binding pockets.
Only certain molecules fit in well and can bind. Binding of chiral
biomolecules is stereospecific.

• A glucose molecule fits into a pocket on the surface of the enzyme

hexokinase (PDB ID 3B8A) and is held in this orientation by several
noncovalent interactions between the protein and the sugar. 31

1.4.8. The Energetics of Life

 Organisms perform energy transductions to accomplish work to stay
alive:

• Living organisms exist in a dynamic steady state and are never at

equilibrium with their surroundings.
• Energy coupling allows living organisms to transform matter into
energy.
• Biological catalysts reduce energy requirement for reactions while
offering specificity.
• As the entropy of the universe increases, creating and maintaining
order requires work and energy.

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1.4.8. The Energetics of Life

 How can biological systems speed reactions up?

• Higher temperatures
− stability of macromolecules is limi ng

• Higher concentration of reactants

− costly, as more valuable star ng material is needed

• Changing the reaction by coupling to a fast one

− universally used by living organisms

• Lower activation barrier by catalysis

− universally used by living organisms

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1.4.8. The Energetics of Life

 Favorable and unfavorable reactions in biological systems.

• Synthesis of complex molecules and many other metabolic reactions

requires energy (endergonic).
o A reaction might be thermodynamically unfavorable (G°> 0).
 Creating order requires work and energy.
‡
o A metabolic reaction might have too high an energy barrier (G > 0).
 Metabolite is kinetically stable.

• The breakdown of some metabolites releases a significant amount of

energy (exergonic).
o Such metabolites (ATP, NADH, NADPH) can be synthesized using the
energy from sunlight and fuels.
o Their cellular concentration is far higher than their equilibrium
concentration.

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1.4.8. The Energetics of Life

 Unfavorable reactions are enabled by energy coupling.
• Chemical coupling of exergonic and endergonic reactions allows
otherwise unfavorable reactions.
• The “high-energy” molecule (ATP) reacts directly with the metabolite
that needs “activation.”
• Adenosine triphosphate (ATP)
provides energy. The removal of
the terminal phosphoryl group of
ATP, by breakage of a phospho-
anhydride bond to generate
adenosine diphosphate (ADP)
and inorganic phosphate ion
(HPO42-), is highly exergonic, and
this reaction is coupled to many
endergonic reactions in the cell.

• ATP also provides energy for many cellular processes by undergoing cleavage
that releases the two terminal phosphates as inorganic pyrophosphate
(H2P2O72), often abbreviated PPi.
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1.4.8. The Energetics of Life

 Enzymatic catalysis.

• A catalyst is a compound that increases the rate of a chemical reaction.

‡
• Catalysts lower the activation free energy G .

• Catalysts do not alter G°.

• Enzymatic catalysis offers:

– acceleration under mild conditions
– high specificity
– possibility for regulation

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1.4.8. The Energetics of Life

 Enzymes lower the activation energy to increase the reaction rate.

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1.4.8. The Energetics of Life

 Series of related enzymatically catalyzed reactions forms a pathway.

• Metabolic pathway
o produces energy or valuable materials

• Signal transduction pathway

o transmits information

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1.4.8. The Energetics of Life

 Pathways are controlled in order to regulate levels of metabolites

enzyme 5

• Example of a negative regulation: Product of enzyme 5 inhibits enzyme

1 to prevent wasteful excess products.

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1.5. The Central “Dogma” of Molecular Biology

DNA → RNA → Protein
 DNA to RNA to protein to enzyme
(hexokinase):
i. The linear sequence of deoxy-
ribonucleotides in the DNA (the gene)
that encodes the protein hexokinase is
first transcribed into a ribonucleic acid
(RNA) molecule with the complementary
ribonucleotide sequence.
ii. The RNA sequence (messenger RNA) is
then translated into the linear protein
chain of hexokinase, which folds into its
native three-dimensional shape, most
likely aided by molecular chaperones.
iii. Once in its native form, hexokinase
acquires its catalytic activity: it can
catalyze the phosphorylation of glucose,
using ATP as the phosphoryl group donor.
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Reading List

• Pratt: Chapter 1, p. 1-14

• Lehninger: Chapter 1, Sections 1.1-1.3
• Voet: Chapter 1, p. 1-17

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