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2 The Composition of Cells
BL 424 Ch. 2 Review Composition of Cells
Cell biology seeks to understand cellular processes
in terms of chemical, physical reactions
Student Learning Outcomes:
A. To describe molecular composition of cells:
Carbohydrates, lipids, nucleic acids, proteins
Draw phospholipid structures, sugars, amino acid
B. To explain structure, function of cell membranes:
Lipids as barriers, phospholipid bilayer
Proteins permit transport of substances
C. To define Proteomics:
•
Large-scale analysis of cell proteins
The Molecules of Cells
The Molecules of Cells
Water is 70% or more of total cell mass.
Water is polar: H atoms slight + charge; O slight – charge
Water molecules form hydrogen bonds:
with each other, or with other polar molecules
Hydrophilic molecules (ions, polar) are soluble
Hydrophobic molecules (nonpolar) are not soluble
Organic molecules:
mostly carbohydrates,
lipids, proteins,
or nucleic acids.
Fig. 2.1
Monosaccharides
1. Carbohydrates: simple sugars, polysaccharides
Monosaccharides join together by glycosidic bond→
disaccharide [dehydration reactions (H2O is removed)]
Monosaccharides (simple sugars) are major
nutrients [basic formula (CH2O)n ]
Oligosaccharides:
Polymers, a few sugars
Glucose (C6H12O6):
principal source of energy,
substrate for biosynthesis
of other macromolecules
Polysaccharides
macromolecules;
hundreds or
thousands of sugars
Fig. 2.2
Fig. 2.3
C1 to C4
α1-4 bond
1
Figure 2.4 Polysaccharides
Glycogen: storage form in animal cells. C1-4
Starch: storage in plant cells.
•
glucose molecules in α configuration: mostly α1-4, some 1-6
Cellulose structural component of plant cell wall.
•
glucose in β configuration; (β1→4) – long chains, strong fibers
.
The Molecules of Cells
2. Lipids have three main roles:
Energy storage
• Fats (triglycerides)
Major components of cell membranes
• Phospholipids, glycolipids,
• Sphingomyelin, cholesterol
Important in cell signaling:
• steroid hormones (estrogen)
• messenger molecules (PIP3)
Fig. 2.4
Figure 2.5 Structure of fatty acids
Fatty acids are simplest lipids: long hydrocarbon
chains (16 or 18 C) with (COO−) at one end.
Hydrocarbon chain is hydrophobic (lot of C, H)
Unsaturated fatty acids:
one or more
double bonds
(kink structure)
Saturated fatty acids:
no double bonds.
Fig. 2.5
Figure 2.6 Structure of triacylglycerols
Fatty acids stored as triacylglycerols, or fats:
3 fatty acids linked to 3-C glycerol (ester link):
Insoluble in water, accumulate as fat droplets;
broken down for energy-yielding reactions.
Fats: more efficient
energy storage
than carbohydrates:
yield more than
twice as much
energy per weight.
Fig. 2.6 triacylglycerol,
triglyceride
2
Figure 2.7 Structure of phospholipids (Part 1)
Figure 2.7 Structure of phospholipids (Parts 2- 3)
• Phospholipids: principal components of cell
membranes: 2 fatty acids joined to polar head group
Glycerol phospholipids:
• 2 fatty acids bound to
C in glycerol.
• 3rd C of glycerol
bound to PO4 head group
* Phosphatidyl-inositol has
sugar inositol; is also signaling
molecule
Sphingomyelin has serine,
(amino acid) instead of glycerol
Common head groups:
Phosphatidyl-ethanolamine
Phosphatidyl-serine
Phosphatidyl-choline
Fig. 2.7
Phospholipids are amphipathic:
hydrophobic tails, hydrophilic head groups;
part water-soluble and part water-insoluble:
basis for formation of biological membranes
Fig. 2.7
Figure 2.8 Structure of glycolipids
Figure 2.9 Cholesterol and steroid hormones
Many cell membranes contain cholesterol
Many membranes have
Glycolipids
4 hydrocarbon rings strongly hydrophobic, but
-OH group on one end is weakly hydrophilic,
so cholesterol is amphipathic
Glycolipids are Amphipathic:
Sugar, fatty acids, no phosphate
steroid hormones
Fig. 2.8
[Note: Archaeal membranes are very different:
ether linkages between glycerol and hydrocarbon
isoprene units; see handout]
(e.g., estrogens and
testosterone)
are derivatives
of cholesterol.
Fig. 2.9
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The Molecules of Cells
The Molecules of Cells
3. Nucleic acids
• Deoxyribonucleic acid (DNA) is genetic material
•
Information specifies proteins via mRNA and triplet code
• Ribonucleic acid (RNA):
Messenger RNA (mRNA) - from DNA to ribosomes
Ribosomal RNA, transfer RNA for protein synthesis.
• RNA can catalyze chemical reactions: (ribozymes).
Two important nucleotides:
DNA and RNA: polymers of nucleotides (purine and
pyrimidine bases linked to phosphorylated sugars)
DNA: adenine and guanine
cytosine and thymine
RNA has uracil
in place of thymine
• Adenosine 5′-triphosphate (ATP), chemical energy form
• Cyclic AMP (cAMP), signaling molecule within cells
ATP
Fig. 2.10
cAMP
Figure 2.10 Components of nucleic acids (Part 2)
• Bases linked to sugars are nucleosides.
• RNA has ribose; DNA has sugar 2′-deoxyribose
• Nucleotides have one or more phosphate groups
linked to 5′ carbon of sugars
Figure 2.11 Polymerization of nucleotides
• Phosphodiester bonds: polymerization between 5′
phosphate of one nucleotide, 3′ hydroxyl of another
• Oligonucleotides: small polymers of a few nucleotides.
• Polynucleotides: RNA and DNA, thousands or millions
• 5’ and 3’
Fig. 2.10
Fig. 2.11
• one end of chain 5′ phosphate group
• other end in 3′ hydroxyl group
• synthesized in 5′ to 3′ direction
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Figure 2.12 Complementary pairing between nucleic acid bases
DNA - double-stranded molecule, 2 chains.
• Bases on inside joined by H bonds between
complementary base pairs: G-C and A-T (A-U)
The Molecules of Cells
4. Proteins – the most diverse macromolecules.
Thousands of different proteins direct cell activities:
• Complementary base
pairing → 1 strand of DNA
(or RNA) acts as template
for synthesis of
complementary strand.
• Nucleic acids are capable of
self-replication
Fig. 2.12
• Information of DNA and
RNA directs synthesis of
proteins, which control most
cell activities.
Figure 2.13 Structure of amino acids
Amino acids
• Each has α carbon bonded to carboxyl group (COO−),
amino group (NH3+), hydrogen, and side chain.
• Grouped based on characteristics of side chains (side
chains confer properties):
–
–
–
–
Nonpolar side chains
Polar side chains
Side chains with basic groups
Acidic side chains terminate
in carboxyl groups
Structural components
Transport and storage of small molecules (e.g. O2)
Transmit information between cells (protein
hormones),
Defense against infection (antibodies)
Enzymes
Proteins are polymers of 20 different amino acids
Figure 2.14 The amino acids
Amino acids grouped based on characteristics of side
chains (Side chains confer properties):
Note: Ser, Thr, Tyr
have –OH group,
can get PO4 added
Fig. 2.13*
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Figure 2.15 Formation of a peptide bond
Peptide bonds join amino acids
Polypeptides are chains of amino acids, hundreds or
thousands of amino acids in length.
• 1st aa is amino group (N terminus)
• Last aa is α carboxyl group (C terminus)
• Sequence of aa defines
characteristics of protein
Figure 2.17 Protein denaturation and refolding
Unique sequence of amino acids in protein is
determined by order of nucleotide bases in gene.
Protein’s 3-D structure is critical to its function:
• shape and function of protein is determined by amino acid
sequence (primary structure)
• 3-D results from interactions between amino acid side chains
Fig. 2.16 insulin has
S-S bond between chains
Fig. 2.17 RNase can
renature after denatured
Fig. 2.15
Figure 2.20 Tertiary structure of ribonuclease, 2.21 quaternary
The Molecules of Cells
Protein structure 4 levels:
Primary structure:
sequence of amino acids
Secondary structure: regular arrangement of amino
acids within localized regions (α helix, β sheet)
Tertiary structure: folding of polypeptide chain from
interactions between side chains in different regions.
– results in domains, basic units of tertiary structure
Quaternary structure: interactions between different polypeptide
chains in proteins composed of more than one polypeptide
RNase
Tertiary structure: interactions between side chains of
amino acids in different regions of primary sequence.
Quaternary structure: interactions between different
polypeptide chains, in proteins composed of more than
one polypeptide.
Tertiary: Hydrophobic amino
acids in interior;
Hydrophilic amino acids on
surface, interact with water.
Hemoglobin – 2α, 2β
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A phospholipid bilayer
B. Cell membranes common structural organization:
phospholipid bilayers with associated proteins.
• Phospholipids spontaneously form bilayers in aqueous
solutions: stable barrier between aqueous compartments
• Lipid bilayers behave as 2-dimensional fluids: individual
molecules can rotate and move laterally - not flip-flop
• Fluidity determined by temperature, lipid composition.
Lipid content of cell membranes varies (Table 1).
Mammalian plasma membranes: mostly 4 major phospholipids
• Animal cells also contain glycolipids and cholesterol
• Organelle membranes have different composition
• Even different lipids on inner, outer surface membrane
Fig. 2.22
Fig. 2.23
Figure 2.24 Insertion of cholesterol in a membrane
Ring structure of cholesterol helps determine
membrane fluidity:
Interactions between
hydrocarbon rings and
fatty acid tails makes
membrane more rigid.
Cholesterol reduces interaction
between fatty acids,
maintains membrane
fluidity at lower temperatures.
The Structure of Cell Membranes: The lipid-globular protein mosaic model
• Fluid mosaic model of membrane structure
(Singer & Nicolson,1972):
• nonpolar parts of membrane proteins sequestered
within membrane
• polar groups exposed to aqueous environment
Key experiment 2.2
Fig. 2.23
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Figure 2.25 Fluid mosaic model of membrane structure
• Integral membrane proteins embedded in lipid bilayer.
• Peripheral membrane proteins associated indirectly interact with integral membrane proteins.
• Transmembrane proteins
- integral proteins
span lipid bilayer,
(α-helical)
with portions
exposed on
both sides
Carbohydrates on
outside proteins
Figure 2.26 Structure of a β-barrel
• Membrane-spanning portions
of transmembrane proteins
usually α-helical regions of 20
to 25 nonpolar amino acids
• Some membrane-spanning
proteins have β-barrel,
folding of β sheets into
barrel-like structure
(some bacteria,
chloroplasts, mitochondria).
Fig. 2.25, 2.26
α-helix, β-barrel
Fig. 2.25**
Figure 2.27 Permeability of phospholipid bilayers
Selective permeability of membranes allows cell to
control its internal composition.
• Some molecules diffuse across bilayer: CO2, O2, H2O.
• Ions, larger uncharged molecules such as glucose, not diffuse
Figure 2.28 Channel and carrier proteins
Transmembrane proteins act as transporters
Channel proteins open pores across membrane.
• selectively open and close in response to extracellular signals
Carrier proteins
selectively bind,
transport specific
small molecules,
such as glucose
• conformational changes
open channels
Much more in Chapt. 13
Fig. 2.27
Fig. 2.28
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Figure 2.29 Model of active transport
Passive transport: molecule movement across membrane
determined by concentration and electrochemical gradients.
Active transport: molecules transported against
concentration gradient coupled to ATP hydrolysis
ex. export of H+ or Na+ from cell
C. Proteomics: Large-Scale Analysis of Cell Proteins
C. Large-scale experimental approaches to
understand complexities of biological systems.
Genomics: systematic analysis of cell genomes all the DNA of organism
Proteomics: systematic analysis to identify all cell
proteins, where they are expressed, and interactions
•
•
•
Fig. 2.29
Active transport
•
Number of genes expressed in any cell is ~ 10,000.
Alternative splicing, protein modifications, → more than
100,000 different proteins
Look at different tissues, time of development, cancer cells
New tools permit these analyses
Figure 2.30 Two-dimensional gel electrophoresis
Figure 2.31 Identification of proteins by mass spectrometry
• Two-dimensional gel electrophoresis does largescale separation of cell proteins:
Mass spectrometry identifies excised proteins:
• Proteins separated based on charge and size.
• Biased toward the most abundant proteins.
Fig. 2.30
• protease cleaves protein into small peptides; then ionized,
analyzed in mass spectrometer (determines the mass-tocharge ratio of each peptide).
• mass spectrum compared to database of known spectra
says which peptide.
Fig. 2.31
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Proteomics: Large-Scale Analysis of Cell Proteins
Proteomics: Large-Scale Analysis of Cell Proteins
Proteomics goals include locations of proteins in cells
• Organelles can be isolated by subcellular fractionation;
Networks (interactome): Protein function requires
proteins then analyzed by mass spectrometry
• Yeast strains in which each protein has been tagged by
fusion with GFP (Fluorescence microscopy).
interacting with other proteins in complexes
• Systematic analysis of protein complexes important goal:
• Isolate proteins under gentle conditions
so complexes not disrupted.
• Analyze protein complexes
by mass spec
• Also screen with antibodies for
co-immuno-precipitation
• Genetic screens for in vivo protein
interactions use yeast two-hybrid
technique
Fig. 2.32
Fig. 2.33
Drosophila
Figure 2.33 A protein interaction map of Drosophila melanogaster
Review questions:
• What was new material in this section?
• Diagram the structure of a phospholipid and a fat
• Diagram ribose, deoxyribose, numbering Carbons
3. What are the major functions of fats and
phospholipids in cells?
6. What experimental evidence showed that the
primary sequence of amino acids contains the
information for folding of the protein?
8. What are the biological roles of cholesterol?
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