The Cell and Its Functions

UNIT I

Textbook of Medical Physiology, 11th Edition

Chapter 2:
The Cell and its Functions
Slides by John E. Hall, Ph.D. and Louise C. Nuttle, Ph.D.

GUYTON & HALL
Copyright © 2006 by Elsevier, Inc.

Organization of the Cell

Figure 2-1


Cell Composition

Water ...70-85% of cell mass
Ions
Proteins ...10-20%
Lipids ...2-95%
Carbohydrates ...1-6%


Membrane Components:
LIPIDS:
• barrier to water and water-soluble substances
• organized in a bilayer of phospholipid molecules
CO2
N2 O2
ions glucose H2O
urea halothane

hydrophilic
“head”
hydrophobic
FA “tail”


Cell Membrane:
Bilayer of Phospholipids with Proteins

Figure 2-3


Proteins:
• provide “specificity” to a membrane
• defined by mode of association with the lipid bilayer
– integral: channels, pores, carriers, enzymes, etc.
– peripheral: enzymes, intracellular signal mediators

K+


Carbohydrates:
• glycolipids (approx. 10%)
• glycoproteins (majority of integral proteins)
• proteoglycans

GLYCOCALYX


Carbohydrates (Cont.):
• negative charge of the carbo chains repels other
negative charges
• involved in cell-cell attachments/interactions
• play a role in immune reactions

(-) (-) (-)
(-) (-)
GLYCOCALYX (-)
(-)


Cholesterol:
• present in membranes in varying amounts
• generally decreases membrane FLUIDITY and
PERMEABILITY (except in plasma membrane)
• increases membrane FLEXIBILITY and STABILITY

(-) (-) (-)
(-) (-)
(-)
(-)


Cell Organelles

Figure 2-2

The Endoplasmic Reticulum:
• Network of tubular and flat vesicular structures
• Membrane is similar to (and contiguous with) the plasma membrane
• Space inside the tubules is called the endoplasmic matrix

Figure 2-4

Rough or Granular ER
• outer membrane surface
covered with ribosomes

• newly synthesized
proteins are extruded into
the ER matrix

• proteins are “processed”
inside the matrix
- crosslinked
- folded
- glycosylated (N-linked)
- cleaved
Figure 2-13

Smooth ER

• site of lipid synthesis
- phospholipids
- cholesterol

• growing ER membrane
buds continuously
forming transport
vesicles, most of which
migrate to the Golgi
apparatus

Figure 2-13


The Golgi Apparatus:

• Membrane
composition similar
to that of the smooth
ER and plasma
membrane
• Composed of 4 or
more stacked layers
of flat vesicular
structures

Figure 2-5


• Receives transport vesicles
from smooth ER

• Substances formed in the ER
are “processed”
- phosphorylated
- glycosylated

• Substances are concentrated,
sorted and packaged for
secretion.


Exocytosis:

Secretory vesicles diffuse
through the cytosol and
fuse to the plasma
membrane

Lysosomes fuse with
internal endocytotic
vesicles


Secretion:
• secretory vesicles
containing proteins
synthesized in the RER bud
from the Golgi apparatus

• fuse with plasma membrane
to release contents
- constitutive secretion -
happens randomly
- stimulated secretion -
requires trigger


Lysosomes:
• vesicular organelle formed from budding Golgi

• contain hydrolytic enzymes (acid hydrolases)
- phosphatases
- nucleases
- proteases
- lipid-degrading enzymes
- lysozymes digest bacteria

• fuse with pinocytotic or
phagocytotic vesicles to form
digestive vesicles

Figure 2-12

Lysosomal Storage Diseases

Absence of one or more hydrolases
• not synthesized
• inactive
• not properly sorted and packaged

Result: Lysosomes become engorged with undigested substrate

Examples:
• Acid lipase A deficiency
• I-cell disease (non-specific)
• Tay-Sachs disease (HEX A)


Peroxisomes:

• similar physically to lysosomes

• two major differences:
• formed by self-replication
• they contain oxidases

Function: oxidize substances (e.g. alcohol) that
may be otherwise poisonous


Secretory Granules

Figure 2-6


Mitochondria
: Primary function: extraction of energy from nutrients

Copyright © 2006 by Elsevier, Inc. Figure 2-7

The Nucleus: “Control Center” of the Cell
The double nuclear membrane and matrix are
contiguous with the endoplasmic reticulum


The nuclear membrane is permeated by
thousands of nuclear pores

• 100 nm in diameter

• functional diameter
is ~9 nm

• (selectively)
permeable to
molecules of up to
44,000 MW

Figure 2-9


Chromatin (condensed DNA) is found in the nucleoplasm
Nucleolus
• one or more per nucleus
• contains RNA and proteins
• not membrane delimited
• functions to form the granular “subunits” of ribosomes


Receptor-mediated endocytosis:

• molecules attach to cell-
surface receptors
concentrated in clathrin-
coated pits

• receptor binding induces
invagination

• also ATP-dependent and
involves recruitment of
actin and myosin

Figure 2-11


Digestion of Substances in
Pinocytotic or Phagocytic Vesicles

Figure 2-12

ATP production
Step 1.
• Carbohydrates are converted
into glucose
• Proteins are converted into
amino acids
• Fats are converted into
fatty acids

Step 2.
• Glucose, AA, and FA are
processed into AcetylCoA

Step 3. A maximum of 38 molecules of
• AcetylCoA reacts with O2 to ATP are formed per molecule of
produce ATP glucose degraded.

(More in Chapter 67)

The Use of ATP for Cellular Function
• under “standard” conditions ∆G° is only -7.3 kcal/mole
• ATP concentration is ~10x that of ADP, the ∆G is -12 kcal/mole

1. Membrane
transport
2. Synthesis of
chemical
compounds
3. Mechanical
work

Figure 2-15

The Cytoskeleton
Intermediate Filaments:
• Comprised of cell-specific fibrillar monomers
(e.g. vimentin, neurofilament proteins, keratins, nuclear
lamins)
Microtubules:
• Heterodimers of α and β tubulin
• Make up spindle fibers, core of axoneme structure

Thin Filaments:
• F-Actin
• Make up “stress fibers” in non-muscle cells

Thick Filaments:
• Myosin (types I and II)
• Together with actin support cellular locomotion and
subcellular transport

Cilia and Ciliary Movements:
• Occurs only on the inside surfaces
of the human airway and fallopian
tubes
• Each cilium is comprised of
11 microtubules
• 9 double tubules
• 2 single tubules axoneme
• Each cilium is an outgrowth of
the basal body and is covered by
an outcropping of the plasma
membrane.
• Ciliary movement is
ATP-dependent
(also requires Ca2+ and Mg2+)
Figure 2-17

Ameboid Locomotion:
• continual endocytosis at the “tail”and exocytosis at the leading edge of
the pseudopodium

• attachment of the pseudopodium is facilitated by receptor proteins carried
by vesicles

• forward movement
results through interaction
of actin and myosin
(ATP-dependent)


Cell movement is influenced by
chemical substances…

Chemotaxis

Low concentration high concentration
(negative) (positive)


UNIT I

Textbook of Medical Physiology, 11th Edition

Chapter 3:
Genetic Control of Protein Synthesis,
Cell Function, and Cell Reproduction
Slides by John E. Hall, Ph.D. and Louise C. Nuttle, Ph.D.

GUYTON & HALL

Central Dogma of Molecular Biology

DNA (genes)

RNA

Proteins

Structural Enzymes

Cell function
Figure 3-2


Transcription:

Figure 3-7


Overview:
Step 1. RNA polymerase binds to the promoter sequence.
Step 2. The RNA polymerase temporarily “unwinds” the
DNA double helix.
Step 3. The polymerase “reads” the DNA strand and adds
complementary RNA molecules to the DNA template.
Step 4. “Activated” RNA molecules react with the growing
end of the RNA strand and are added (3’ end).
Step 5. Transcription ends when the RNA polymerase
reaches a chain terminating sequence, releasing both
the polymerase and the RNA strand.


Messenger RNA:
• complementary in sequence to the DNA coding strand

• 100’s to 1000’s of nucleotides per strand

• organized in codons - triplet bases
- each codon “codes” for one amino acid (AA)
- each AA - except met- is coded for by multiple codons
- start codon: AUG (specific for met)
- stop codons: UAA, UAG, UGA


The Process of
Translation
nuclear plasma
envelope membrane

NUCLEUS DNA (genes)
DNA
DNA
TRANSCRIPTION
RNA RNA
RNA
SPLICING Proteins

RNA TRANSPORT Structural Enzymes
TRANSLATION OF
ribosomes MESSENGER RNA

protein Cell function
CYTOSOL


Transfer RNA
• acts as a carrier molecule during protein synthesis
• each transfer RNA (tRNA) combines with one AA
• each tRNA recognizes a specific codon by way of a
complementary
anticodon on the
tRNA molecule

Figure 3-9

Ribosomes
Polyribosomes: multiple ribosomes can simultaneously
translate a single mRNA

Figure 3-11


Chemical Events in Protein Formation

Figure 3-11

Overview :Protein Formation
Phase 1: Initiation

• small ribosomal subunit and initiator tRNA (Met)
complex binds to 5’end of an mRNA chain

• this complex moves along mRNA molecule until
it encounters a start codon (AUG)

• initiation factors dissociate and large ribosomal
subunit binds


Phase 2: Elongation
• AA-tRNA binds to the ribosomal A-site

• peptidyl transferase joins the tRNA at the P-site to
the AA linked to the tRNA at the A-site with a
peptide bond

• the new peptidyl-tRNA is translocated from the
A-site to the P-site


Phase 3: Termination

• Release factor binds to the stop codon.

• Completed polypeptide is released.

• Ribosome dissociates into its 2 subunits.


Control of Genetic Function
and Biochemical Activity

DNA (genes) transcription
processing
transport to cytosol RNA
translation
mRNA stability
Proteins

Structural Enzymes protein activity

Cell function


Genomics

Genomics: the large-scale study of
the genome

• Recent estimates suggest ~ 30,000 genes

• Humans are 99.8% identical at the genome
level, 99.999% identical in the coding regions


identify a gene

determine nucleic acid sequence
(sequence homology?)
Bioinformatics
determine amino acid sequence
(fold homology?)

best guess...


Proteomics

Proteomics: the large-scale analysis of
proteins (i.e. the proteome)

• “Proteome” describes the protein composition
of a cell

• approximately 10,000 proteins per cell, or ~15%
of total possible gene products

Genome ≠ Proteome

Transcriptional Control:
The Operon: a procaryote model
• series of
genes and
their shared
regulatory
elements

• gene
products
contribute
to a common
process
Figure 3-12


Negative Regulation

• sequences called “repressor operators” bind repressor
proteins

• binding interferes with the ability of the RNA
polymerase to bind to the promoter

NO TRANSCRIPTION


Positive Regulation

• so-called “activator operators” bind activator
proteins

• binding facilitates the association of the RNA
polymerase with the promoter

ENHANCED TRANSCRIPTION


Genetic Control of Cell Reproduction

Life Cycle of the Cell:

M
M phase:
(mitosis) • mitosis
G2 • cytokinesis
(Gap 2) G1
(Gap 1)
EUKARYOTIC Interphase (>95%):
CELL CYCLE
Cells that • G1 phase
cease • S phase (DNA synthesis)
division • G2 phase
S phase
(DNA synthesis)

DNA Replication: S phase
• switched on by the cytoplasmic S-phase activator

• Replication is initiated at replication origin and
proceeds in both directions.

• Entire genome is replicated once - further replication
is blocked

• involves DNA polymerase and other proteins that
function to unwind and stabilize the DNA and
“prime” DNA replication of the “lagging” strand.

DNA Replication: S phase
• nucleotides are always added to the 3’ end
(DNA and RNA)

• formation of Okazaki fragments on lagging strand

• “new” DNA is proofread by DNA polymerase

• repairs are made and gaps filled by DNA ligase


Chromosomes and Their Replication

• “New” DNA helices associate with histones to form
chromosomes

• The two chromosomes remain temporarily attached
at the centromere.

• Together, these chromosomes are called chromatids.


Stages of Cell Reproduction

Mitosis: M phase

1. Assembly of the mitotic
apparatus
2. Prophase (A,B,C)
3. Prometaphase (D)
4. Metaphase (E)
5. Anaphase (F)
6. Telophase (G, H)


Control of Cell Growth

What determines the rate of cell growth?
• growth factors
• contact inhibition
• cellular secretions (negative feedback)

RAPID: bone marrow, skin, intestinal epithelia
SLOW/NEVER: smooth muscle, neurons, striated muscle


Cell Differentiation

Different from reproduction ...
• changes in physical and functional properties of
cells as they proliferate

• results not from the loss of genes but from the
selective repression/expression of specific genes

• development occurs in large part as a result of
“inductions,” one part of the body affecting another


Cancer

Dysregulation of cell growth

Caused in all or almost all cases by the mutation or
abnormal activation of genes that encode proteins that
control cell growth and/or mitosis

• Proto-oncogenes: the “normal” genes
• Oncogenes: the “abnormal” gene
• Antioncogenes: genes whose product suppress the
activation of oncogenes

Not all mutations lead to cancer!

What causes these mutations?

• Ionizing radiation: disrupts DNA strands

• Chemicals: “carcinogens”

• Physical irritants: e.g., abrasion of the intestinal lining

• Hereditary “tendencies”: e.g., some breast cancer

• Viruses: so-called “tumor viruses” (particularly
retroviruses)


Q: Why does cancer kill?

A: Cancer cells compete
successfully with normal cells
for limited nutrients


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