08-07 Introduction to Physiology- The Cell and General Physiology.pdf

Na

1. Functional Organization of the
Human Body and Control of
the “Internal Environment”

Rodolfo T. Rafael,M.D.,DPAAB, FPAFP

Faculty President
Professor 1

2. + Define human physiology.

+ Recognize cells are the living
units of the body.

+ Discuss internal environment of
the human body.

+ Explain the maintenance of a
nearly constant internal
environment.

+ Review of the control system of
the body.

3. * The science of human physiology
attempts to explain the specific
Human characteristics and mechanisms

A of the human body that make it a

Physiology living being.

4. CELLS ARE THE LIVING
UNITS OF THE BODY

5. Cells as the Living Units of the Body

CELLULAR LEVEL - cells are the basic structural and
functional units of the human body & there are many different
types of cells (e.g., muscle, nerve, blood, and so on)

ah

Sperm cell

Nerve cell

Muscle cell Hair
cell

6. Basic Characteristics

= In all cells, oxygen reacts with carbohydrate, fat,
and protein to release the energy required for
cell function.

= General chemical mechanisms for changing
nutrients into energy ate basically the same in all
cells

m All cells deliver end products of their chemical
reactions into the surrounding fluids.

= Almost all cells have the ability to reproduce
their own kind

7. ©

Intracellular
fluid (ICF)

Interstitial
fluid

Extracellular
fluid (ECF)

Is in constant motion throughout the body.

EXTRACELLULAR FLUID—THE fons and nutren

milieu intérieur, a term introduced more

“INTERNAL ENVIRONMENT” | Sorisovengspo tre ew

century French physiologist Claude
Bernard (1813-1878).

8. A
Differences between ECF and ICF

Cations:
Na* (142mmov)
DK: (4.2)

Nutrients:
ns O,, glucose, fatty acids, &
amino acids.

Nutrients:
A High concentrations of proteins.

D Wastes:

CO,, Urea, uric acid,

excess water, & ions.

9. HOMEOSTASIS—MAINTENANCE OF A
NEARLY CONSTANT INTERNAL
ENVIRONMENT

1929 the American physiologist Walter Cannon (1871-1945)
coined the term homeostasis to describe the maintenance of

nearly constant conditions in the internal environment.

10. Arteriole

Figure 1-2. Diffusion of fluid and dissolved constituents through the
capillary walls and through the interstitial spaces.

EXTRACELLULAR FLUID TRANSPORT AND MIXING
SYSTEM—THE BLOOD CIRCULATORY SYSTEM

11. ORIGIN OF
NUTRIENTS
IN THE

EXTRACELL
ULAR FLUID

Figure 1-1. General organization ofthe circulatory system,

o acids

12. + Removal of Carbon Dioxide

Kidneys

© CO2, urea, uric acid, etc.

* waste products of metabolism are
eliminated in the feces

+ detoxification or removal of many
drugs and chemicals that are
ingested

13. REGULATION OF BODY FUNCTIONS

Nervous System- major parts: the sensory input Hormone System- thyroid hormone, Insulin,
portion, the central nervous system (or integrative adrenocortical hormones, parathyroid hormone
portion), and the motor output portion.

14. PROTECTION OF THE BODY

Immune System

distinguish its own cells from foreign
cells and substances

destroy the invader by phagocytosis or
by producing sensitized lymphocytes or
specialized proteins (e.g., antibodies)
that either destroy or neutralize the
invader

Integumentary System

temperature regulation and excretion of
wastes

provides a sensory interface between the
body and the external environment

15. REPRODUCTION

* Sometimes reproduction is not considered a homeostatic
function.

* It does, however, help maintain homeostasis by generating
new beings to take the place of those that are dying.

16. CONTROL SYSTEMS OF THE

BODY

The human body has thousands of control systems.

17. EXAMPLES
OF
CONTROL

MECHANI
SMS

18. Normal Value
40
45
142
42
12

984 (37.0)
74

10-14
103-112

98-983 (37.0)
7375

Approximate Short-Term Nonlethal Limit
10-1000

115-175

mm Hg
mm Hg

19. CHARACTERISTICS OF CONTROL SYSTEMS

m w de o

Pumping effectiveness of heart
(Liters pumped per minute)

Hours

* Recovery of heart pumping caused by negative feedback after 1 liter of
blood is removed from the circulation.

+ Death is caused by positive feedback when 2 liters of blood are removed.

20. SUMMARY—AUTOMATICITY OF
Lu BODY

Body is a social order of about 100 trillion cells organized into different
functional structures, some of which are called organs.

+ Each functional structure contributes its share to the maintenance of
homeostatic conditions in the extracellular fluid, which is called the internal
environment.

21. Overview of Cellular

Physiology in
Medical Physiology

Rodolfo T. Rafael, M.D.,FPAFP
Professor 1

22. Objectives:

Name the building

blocks of the cellular
cytoskeleton and state
their contributions to
cell structure and
function

Name the intercellular
and cellular to
extracellular
connections.

Define the proc

endocytosis, and
describe the
contribution of each to
normal cell function

23. + The cell
+ is the fundamental working unit of all
organisms.
+ In humans

INTRODUCTION + highly specialized in both

structure and function

+ cells from different organs can
share features and function.

24. FUNCTIONAL MORPHOLOGY
OF THE CELL

Rough
endoplasmic
reticulum

Nuclear envelope

arti '
(organelles) are common
to most cells

Ye

lobular heads
Bi Globular heat

25. « Isolated by
+ Ultracentrifugation
* Nuclei and mitochondria
* High-speed centrifugation that

FUNCTIONAL generates forces of 100,000 times

gravity or more causes a fraction

MORPHOLOGY made up of granules
OF THE CELL + microsomes
* organelles
* ribosomes
* peroxisomes.

26. CELL MEMBRANES

« lipids and proteins

* semipermeable

+ its permeability varied

* it contains numerous

regulated ion channels and
other transport proteins that
can change the amounts of
substances moving across it
> plasma membrane.

27. CELL MEMBRANES

Common features

7.5 nm (75 A) thick
major lipids are phospholipids
+ phosphatidylcholine
* phosphatidylethanolamine
shape of the phospholipid molecule
reflects its solubility properties
* the head end of the molecule
contains the phosphate portion and
is relatively soluble in water.
+ tails are relatively insoluble
(nonpolar, hydrophobic).
amphipathic molecule.
the hydrophilic ends of the molecules are
exposed to the aqueous environment
the hydrophobic ends meet in the water-
poor interior of the membrane

28. prokaryotes the

impl
membranes ii

glycosphingolipids

sphingomyelin

CELL

MEM BRAN ES eukaryotes (cells

containing nuclei), cholesterol
cell membranes

phospholipids

phosphatidylcholine.

29. CELL MEMBRANES

integral proteins

+ they exist as separate
globular units and many pass
through the membrane

peripheral proteins

+ stud the inside and outside
of the membrane

50% of the mass of the
membrane

one protein molecule
per 50 of the much
smaller phospholipid
molecules.

30. Cell Membrane Protein Types Li eels

have similar

articulated peripheral protein Movements:

protein with Fluid Mosaic
oligosaccharides Model

hydrophilic ¢ cell wall side
hydro-
phobic

hydrophilic (4 A ees As: phospholipid

bilayer

31. CELL MEMBRANES

+ The proteins in the membranes carry out many functions
+ cell adhesion molecules
* pumps
+ carriers
+ ion channels

* Proteins in other group function as
* receptors
* enzymes

* Uncharged

+ hydrophobic portions of the proteins are usually located in the interior of the
membrane

* Charged

* hydrophilic portions are located on the surfaces

32. Cytoplasmic or external face of membrane

NN Gy — rain 3) —coom

— Protein —NH,

ney Soy
SPalmitoyl E
H

AnAKW WK soy Protein —NH,

Geranyigeranyl h
LULA so Protein nn,
Farnesyl H
lo
IIA OO Oo
cH 0

i
ARADO O A
GPI anchor

i 1
10 q-o—+—o—tmei—o—c— E
!

1 LA

(Glycosyiphosphatidyimosito!) d

Hydrophilic domain

!
<— Hydrophobic domain >|.

Q Peripheral proteins attached to the surfaces of the membrane in various ways
Q attachment to glycosylated forms of phosphatidylinositol
Q Proteins held by these glycosylphosphatidylinositol (GPI) anchors include
enzymes such as:
Q alkaline phosphatase
Q various antigens
Q a number of cell adhesion molecules
O three proteins that combat cell lysis by complement.

33. Lipid membrane à Cytoplasmic or external face of membrane

POPOL \N—Gly —4 HL
O ys GRO co
à

ILLIA +0 ER 1,
SPalmitoy! 4

Art tr so EN,

Geranyigerany! H
AAA to CESR
Farnesyl 4
lo
Ml
YAA O Ge
NDA 8 ñ
GPlanchor ¡9 C—o—P—O—Imositoi—O—C—4 Protein
(Gyeosyphosphatdyinastol | [|

<— Hydrophobic domain ———>|< Hydrophilic domain

QO Over 45 GPllinked cell surface been described in humans.

U Other proteins are lipidated

Q Proteins may be myristolated, palmitoylated, or prenylated (ie,

attached to geranylgeranyl or farnesyl groups).

UO The protein structure—and particularly the enzyme content— of
biologic membranes varies not only from cell to cell, but also within the
same cell.

34. + In epithelial cells- polarized

Cell

Membranes + The membranes are dynamic structures.

35. Mitochondria

* Function
* oxidative phosphorylation

* apoptosis ow at
* hundreds to thousands of ~~

mitochondria

retory granules

Bo

* sausage-shaped organelles wal

36. Mitochondria

inter membrane space

cristae

Ribosome

Granules

Inner membrane
‘Outer membrane

® Each has an outer membrane, an intermembrane space, an inner membrane, which is

folded to form shelves (cristae), and a central matrix space.
# The enzyme complexes responsible for oxidative phosphorylation are lined up on the

cristae

37. + mitochondria have their own genome
+ less DNA in the mitochondrial genome
than in the nuclear genome
« 99% of the proteins in the mitochondria
are the products of nuclear genes
+ mitochondrial DNA is responsible for
certain key components of the pathway
for oxidative phosphorylation.
Mitochondria * human mitochondrial DNA
+ double-stranded circular molecule
+ 16,500 base pairs
+ It codes for 13 protein subunits that
are associated with proteins encoded
by nuclear genes to form
* four enzyme complexes plus two
ribosomal and 22 transfer RNAs

38. * The enzyme complexes responsible for
oxidative phosphorylation illustrate the
interactions between the products of the
mitochondrial genome and the nuclear
genome.

+ For example

+ complex I

reduced NADH

made up of 7 protein subunits
coded by mitochondrial DNA
39 subunits coded by nuclear
DNA

+ Complex II, succinate
dehydrogenase-ubiquinone
oxidoreductase;

Complex III, ubiquinone-
cytochrome c oxidoreductase
Complex IV, cytochrome c
oxidase, act with complex I,
coenzyme Q, and cytochrome c
to convert metabolitesto CO,
and water.

+ Complexes |, Ill, and IV pump protons (H*)
into the intermembrane space during
electron transfer.

39. Mitochondria

H+ H+

H+ Ht
Intramemb space
a — CoQ —— Cytc >
membrane A
Matrix space ATP
Iv
3

Complex I ul il Vv

Subunits from 7 0 1 2
mDNA

Subunits from 39 4 10 10 14
nDNA

Components involved in oxidative phosphorylation in mitochondria and their origins.
As enzyme complexes | through IV convert 2-carbon metabolic fragments to CO2 and
H20, protons (H+) are pumped into the intermembrane space.

The proteins diffuse back to the matrix space via complex V, ATP synthase (AS), in which
ADP is converted to ATP.

The enzyme complexes are made up of subunits coded by mitochondrial DNA (mDNA)
and nuclear DNA (nDNA), and the figures document the contribution of each DNA to
the complexes.

40. Complex II

_

Inter-m embrane Space

Inner Mitochondrial
Membrane

Succinate Fumarate

41. Mitochondria

+ Zygote mitochondria
« derived from the ovum
« their inheritance is maternal

+ Mitochondria have an ineffective DNA
repair system, and the mutation rate for
mitochondrial DNA is over 10 times the
rate for nuclear DNA.

+ Large number of relatively rare
diseases have now been traced to
mutations in mitochondrial DNA.

« disorders of tissues with high
metabolic rates

42. SDHA, B, C, D BCSIL SURFI, SCO1,
S002, COX10
Leigh syndrome Hepatopathy Leigh syndrome Cardioencephalo-
Encephalopathy Cardioencephalo- myopathy:
Phaeochromocytoma myopathy Hepatopathy
Hepatopathy

43. Lysosomes

large irregular structures
surrounded by membrane.

+ interior is acidic than the rest of the
cytoplasm
© external material such as endocytosed
bacteria, as well as worn-out cell
components, are digested in them.

44. « Lysosomes can contain over 40
types of hydrolytic enzymes
* acid hydrolases
« function best at the acidic
Lysosomes pH of the lysosomal
compartment
+ What will happen if the lysosome

were to break open and release
its contents?

45. Lysosomes

Enzyme Substrate

Ribonuclease RNA

Deoxyribonuclease DNA

Phosphatase Phosphate esters

Glycosidases Complex carbohydrates; glycosides and
polysaccharides

Arylsulfatases Sulfate esters

Collagenase Collagens

Cathepsins Proteins

Some of the enzymes found in lysosomes and the cell components that are their

substrates.

46. osomes

Lysosomal Diseases

When a lysosomal enzyme is congenitally absent, the lyso-
somes become engorged with the material the enzyme
normally degrades. This eventually leads to one of the lyso-
somal storage diseases. For example, a-galactosidase A
deficiency causes Fabry disease, and B-galactocerebrosi-
dase deficiency causes Gaucher disease. These diseases are
rare, but they are serious and can be fatal. Another example
is the lysosomal storage disease called Tay-Sachs disease,
which causes mental retardation and blindness. Tay-Sachs
is caused by the loss of hexosaminidase A, a lysosomal en-
zyme that catalyzes the biodegradation of gangliosides
(fatty acid derivatives).

47. Peroxisomes

+ 0.5 um in diameter
* surrounded by a membrane

* contain enzymes that can either produce
H,0, (oxidases) or break it down
(catalases).

+ Proteins are directed to the peroxisome
by a unique signal sequence with the
help of protein chaperones, peroxins.

+ Membrane contains a number of
peroxisome-specific proteins that
transport substances into and out of the
matrix

48. + Peroxisomes form by

+ budding of endoplasmic reticulum, or by
division.

+ A number of synthetic compounds were
found to cause proliferation of
peroxisomes by acting on receptors in
the nuclei of cells.

+ These peroxisome proliferation
activated receptors (PPARs) are
Pe roxisomes members of the nuclear receptor
superfamily.

+ When activated, they bind to
DNA, producing changes in the
production of mRNAs.

* The known effects for PPARs are
extensive and can affect most
tissues and organs.

49. © wwmncbinimnihgov/pubn rangos Ea

care2corg A Dictionary, Encyclop... (Z drrodeifersfael- Ya GoogleScholar ¿y Google Translate

ELSEVIER

a Save items
PPAR-gamma agonists: therapeutic role in diabetes, inflammation and cancer.

uh G Holder JC Add to Favortes
Denormert of Vesclr Boy. Sine Beecham Fhomaceutcab.NFSATU. Carter Rose, Herb, Cit19 SAD, Essex US Grea Muphy-1@steh com

Abstract
‘The recent development ofa novel class of insulin-sensitzing drugs. the thiazoiinediones (TZDS). represents a significant advance in antidiabetic
therapy. One key mechanism by which these drugs exe their efects is by activation ofthe peroxisome prlerator activated receptor gamma
(PAR gamma), a member ofthe nuclear receptor ami, Evidence supporting this mechanism of action ofthe TZDe wil be reviewed in this article
Recent data suggests that PPAR-gamma agonists might also have therapeutic potential inthe treatment of infammatory diseases and certain

Related citations in PubMed

PUD. 11121896 Rated indes for EDL »isome y
© Publication Types, MeSH Terms, substances

© LinkOut - more resources

other

50. Cytoskeleton

Cytoskeletal filaments Diameter (nm) Protein subunit
Microfilament 7 Actin
Intermediate filament 10 Several proteins

Microtubule 25 Tubulin

51. Microtubules

Y” long, hollow structures with 5-nm walls surrounding a cavity 15 nm in diameter.
Y” Made up of two globular protein subunits:
o aand f-tubulin.
v Athird subunit,
o y-tubulin
« associated with the production of microtubules by the centrosomes.

52. * The a and B subunits form
+ heterodimers, which aggregate to
form long tubes made up of stacked
rings, with each ring usually
containing 13 subunits.

* The tubules interact with GTP to
facilitate their formation.

+ Microtubule subunits can be added to
either end, microtubules are polar with

* assembly predominating at the "+"
end

+ disassembly predominating at the
EN Gym)

Microtubules

+ Both processes occur simultaneously in
vitro.

* The growth of microtubules
+ temperature sensitive (disassembly
is favored under cold conditions) as
well as under the control of a
variety of cellular factors that can
directly interact with microtubules
in the cell.

53. Microtubules

Dynamic portion of the cell
skeleton

+ because of their constant
assembly and disassembly.

They provide the tracks along
which several different molecular
motors move transport vesicles,
organelles such as secretory
granules, and mitochondria, from
one part of the cell to another.

They also form the spindle, which
moves the chromosomes in
mitosis.

Cargo can be transported in
either direction on microtubules.

54. « There are several drugs available
that disrupt cellular function
through interaction with
microtubules.

+ Microtubule assembly is
prevented by
+ colchicine
« vinblastine.

Microtubules

« The anticancer drug paclitaxel
(Taxol) binds to microtubules and
makes them so stable that
organelles cannot move.

+ Mitotic spindles cannot form,
and the cells die.

55. Intermediate
Filaments

*8 to 14 nm in diameter

« Some of these filaments connect
the nuclear membrane to the cell
membrane.

« They form a flexible scaffolding
for the cell and help it resist
external pressure.

« cells rupture more easily
+ abnormal > blistering of the
skin is common.

« Cellular markers

« vimentin
+ major intermediate filament
in fibroblasts
+ cytokeratin is expressed in
epithelial cells

56. « are long solid fibers
+ 4to 6 nm diameter
+ made up of actin.
* actin is most often associated with

muscle contraction, it is present in all
types of cells.

« abundant protein in mammalian cells

+ 15% of the total protein in the
cell.

Microfilaments

57. Microfilaments

+ Actin filaments polymerize and depolymerize
in vivo
+ polymerization occurring at one end of
the filament
+ depolymerization is occurring at the
other end.
+ Filamentous (F) actin
+ intact microfilaments
+ Globular (G) actin
* unpolymerized protein actin subunits.

+ F-actin fibers attach to various parts of the
cytoskeleton and can interact directly or
indirectly with membrane-bound proteins.

58. Molecular
Motors

* move proteins, organelles, and other cell
parts (collectively referred to as "cargo") to
all parts of the cell .

+ 100 to 500 kDa ATPases
+ They attach to their cargo at one end of the

molecule and to microtubules or actin
polymers with the other end, "head."

+ They convert the energy of ATP into
movement along the cytoskeleton, taking
their cargo with them.

+ There are three super families of molecular
motors:
+ kinesin
+ dynein
* myosin

59. Molecular Motors

Cytoplasmic dynein

60. Kinesin

50
nanometers

Kinesin's

Cellular material
being transported

Cellular “roads by molecular motors

61. Molecular Motors

+ kinesin

+ is a doubleheaded molecule
that tends to move its cargo
toward the "+" ends of
microtubules.
One head binds to the
microtubule and then bends its
neck while the other head
swings forward and binds,
producing almost continuous
movement.
mitosis and meiosis.
Other perform different
functions, including, in some
instances, moving cargo to the
"—" end of microtubules.

62. Molecular Motors

+ Dyneins

* two heads, with their
neck pieces embedded
in a complex of
proteins.

* Cytoplasmic dyneins
have a function like
that of conventional
kinesin, except they
tend to move particles
and membranes to the
"—" end of the
microtubules.

63. Head 1

+ Myosin

+ The multiple forms of myosin
in the body are divided into
18 classes.

The heads of myosin
molecules bind to actin and
produce motion by bending
their neck regions (myosin I!)
or walking along
microfilaments, one head
after the other (myosin V).
they perform functions as
diverse as contraction of
muscle and cell migration.

9
i Cargo-binding domain

Head 2

ADP’ >

Myosin V

Molecular Motors

oa
Head 2
ADP.

Head 1
ATP

Actin

64. Centrosomes

+ Near the nucleus

* two centrioles and surrounding
amorphous pericentriolar material.

* The centrioles are short cylinders
arranged so that they are at right
angles to each other.

* Microtubules in groups of three run
longitudinally in the walls of each
centriole

* Nine of these triplets are spaced at
regular intervals around the
circumference.

+ Microtubule-Organizing Centers (MTOCs)
that contain -tubulin.

+ The microtubules grow out of this -tubulin
in the pericentriolar material.

+ When a cell divides, the centrosomes
duplicate themselves, and the pairs move
apart to the poles of the mitotic spindle,
where they monitor the steps in cell
division. In multinucleate cells, a
centrosome is near each nucleus.

65. Centrosomes

Astral spindle fibers Astral spindle fibers
Centriole Chromosomes Centriole

Chromosomal spindle fibers Polar spindle fibers
Pericentriolar material Pericentriolar material

66. * specialized cellular projections that are used by
* unicellular organisms
+ multicellular organisms
+ functionally indistinct from the eukaryotic
flagella of sperm cells.
* Axoneme
* comprises a unique arrangement of nine
outer microtubule doublets and two inner
microtubules ("9+2" arrangement).
+ axonemal dynein
« Along cytoskeleton
* coordinated dynein-microtubule interactions
within the axoneme are the basis of ciliary
and sperm movement.
+ basal body
* at the base of the axoneme .
* It has nine circumferential triplet
microtubules, like a centriole

evidence that basal bodies and centrioles
are interconvertible.

67. * Cells are attached to the basal lamina and to each
other by CAMs

+ These adhesion proteins have unique structural
and signaling functions

+ important
1. embryonic development and formation
of the nervous system and other tissues

2. in holding tissues together in adults
Cell Adhesion 3. in inflammation and wound healing

4. inthe metastasis of tumors
Molecules (CAMs)
+ Many CAMs pass through the cell membrane and

are anchored to the cytoskeleton inside the cell.
+ Some bind to
+ like molecules on other cells (homophilic
binding)
* nonself molecules (heterophilic binding).

* Many bind to laminins, a family of large cross-
shaped molecules with multiple receptor domains
in the extracellular matrix.

68. Cell Adhesion
Molecules

+ CAMs can be divided into four broad

families:
1. integrins
2. IgG superfamily of
immunoglobulins
3. cadherins
4. selectins

* The CAMs not only fasten cells to their
neighbors, but they also transmit
signals into and out of the cell.

« cells that lose their contact with the
extracellular matrix via integrins
have a higher rate of apoptosis than
anchored cells, and interactions
between integrins and the
cytoskeleton are involved in cell
movement.

69. Intercellular Connections

70. Intercellular Connections

m The desmosome and zonula adherens
o help to hold cells together
u hemidesmosome and focal adhesions
© attach cells to their basal laminas.
m The gap junction forms a cytoplasmic
"tunnel" for diffusion of small molecules
(< 1000 Da) between two neighboring
cells.

Tight junctions
> surround the apical margins of the cells in
epithelia such as
* intestinal mucosa
* the walls of the renal tubules
* choroid plexus.
> important to endothelial barrier function.

71. * Tight Junction
* three main families of
transmembrane proteins that
contribute to tight junctions:
* occludin
junctional adhesion molecules
(JAMs)
+» claudins
* permit the passage of some ions
Intercellular and solute in between adjacent
cells (paracellular pathway) and
the degree of this "leakiness"
varies.
* prevent the movement of proteins
in the plane of the membrane
« help to maintain the different
distribution of transporters and
channels in the apical and
basolateral cell membranes that
make transport across epithelia
possible.

Connections

72. Intercellular Connections

Zonula
Adherens

is usually a continuous
structure on the basal side of
the zonula occludens

a major site of attachment for
intracellular microfilaments

contains cadherins.

are patches characterized by

apposed thickenings of the

membranes of two adjacent
cells.

Attached to the thickened area
in each cell are intermediate
filaments.

Between the two membrane
thickenings the intercellular
space contains filamentous
material that includes
cadherins and the extracellular
portions of several other
transmembrane proteins.

73. « Hemidesmosomes

«look like half-
desmosomes that
attach cells to the
underlying basal
lamina and are
connected
intracellularly to
intermediate filaments

* integrins

Intercellular

Connections

74. Gap Junctions

e narrows from 25
alled connexons in

40)

Each connexon is n
subunits called conn

(TD
(CAD

cell, as well as the exchange of various
chemical messengers

Charcot-Marie-Tooth disease

75. cleus &
Related

ctures

A nucleus is present in all eukaryotic cells that divide.

If a cell is cut> the anucleate portion eventually dies
without dividing.
The nucleus
+ is made up in large part of the chromosomes, the
structures in the nucleus that carry a complete
blueprint for all the heritable species and individual
characteristics of the animal.
The chromosomes
* occur in pairs, except in germ cells one originally from
each parent.
* Each chromosome is made up of a giant molecule of
DNA.
The DNA strand is
+ 2 m long, but it can fit in the nucleus because at
intervals it is wrapped around a core of histone
proteins to form a nucleosome. There are about 25
million nucleosomes in each nucleus.

The whole complex of DNA and proteins is called
chromatin.

76. +» During cell division, the coiling around
histones is loosened
+ by acetylation of the histones, and pairs of
chromosomes become visible.
* Genes
¢ ultimate units of heredity on the
chromosomes.
Nucleus & « each gene is a portion of the DNA
Related molecule.
Structures « The nucleus of most cells contains a o
nucleolus, a patchwork of granules rich in
RNA.
« Nucleoli are most prominent and numerous in
growing cells.
+ the site of synthesis of ribosomes
* the structures in the cytoplasm in which
proteins are synthesized.

77. « The interior of the nucleus has a skeleton of fine
filaments that are attached to the nuclear
membrane, or envelope, which surrounds the
nucleus.

* membrane is a double membrane, and
spaces between the two folds are called
perinuclear cisterns.

* membrane is permeable only to small
molecules.

* it contains nuclear pore complexes.

« There are many transport pathways, and

proteins called importins and exportins have
been isolated and characterized.

* Current research is focused on transport into
and out of the nucleus.

78. + is a complex series of tubules in the cytoplasm of
the cell

+ In rough, or granular, endoplasmic reticulum
+ ribosomes are attached to the cytoplasmic side
of the membrane

* concerned with protein synthesis and the initial
folding of polypeptide chains with the
formation of disulfide bonds.

À | h l i i icul
E ndoplasm ic n mes , or agranular, endoplasmic reticulum
icul + ribosomes are absent.
Reticulum + the site of steroid synthesis in steroid-secreting
cells and the site of detoxification processes in
other cells.

+ Free ribosomes are also found in the cytoplasm.

+ A modified endoplasmic reticulum, the
sarcoplasmic reticulum, plays an important role in
skeletal and cardiac muscle.

* can sequester Ca?* ions and allow for their
release as signaling molecules in the cytosol.

79. Cytoplasm

"0 | |
| }
Sun} | Ÿ |

x Rough

y al
prokaryotic ribosomes (E. coli)
ribosome subunit rRNAs r-proteins
235 (2904 nt) Golgi apparatus
50S 31 a
70S 5S (120 nt)
305 165 (1542 nt) 21 pur
eukaryotic cytosolic ribosomes (R. norvegicus)
ribosome subunit TRNAs r-proteins
Digestive
285 (4718 nt) ES
Gone 8
60S 5.85 (160 nt) 49
805 Plasma membrane
5S (120 nt)

Extracellular fluid

AOS 185 (1874 nt) 33

80. Ribosomes

Y” They are the sites of protein synthesis.

Y” synthesize

Q transmembrane proteins
Q most secreted proteins
Q most proteins that are stored in
the
“* Golgi apparatus
“+ lysosomes
“ endosomes.

Y” proteins typically have a hydrophobic
signal peptide at one end

Y” The polypeptide chains that form
these proteins are extruded into the
endoplasmic reticulum.

Y” The free ribosomes synthesize
cytoplasmic proteins such as
hemoglobin and the proteins found in
peroxisomes and mitochondria

mRNA from Gene A mRNA from Gone B

Fume | o |

4 8 1
EN oe he

Rough
endoplasmic
Fotculum

Catan
Q] group

TER

from Gene A

81. Golgi Apparatus & Vesicular Traffic

ER Golgi apparatus Secretory granules

Regulated secretion
Le
o A

4 ET di

p-

Lysosome Late endosome Early endosome

Endocytosis

Nucleus

82. Golgi Apparatus & Vesicular Traffic

There are usually about six
sacs in each apparatus

83. Vesicular Traffic

* The Golgi apparatus is a polarized structure
* cis and trans sides.

+ Membranous vesicles containing newly
synthesized proteins bud off from the granular
endoplasmic reticulum and fuse with the
cistern on the cis side of the apparatus. >The
proteins are passed via other vesicles to the
middle cisterns and finally to the cistern on the
trans side, from which vesicles branch off into
the cytoplasm. > From the trans Golgi,
vesicles shuttle to the lysosomes and to the
cell exterior via constitutive and
nonconstitutive pathways, both involving
exocytosis.

Conversely, vesicles are pinched off from the
cell membrane by endocytosis and pass to
endosomes they are recycled.

84. End