Lecture 1 Biochem 232 Cells

Biochem-232-DrMowafy-Pharmacy-JU 9/21/2010
Substate
Diabetic retinopathy
Active site
Enzyme
Dr. Abdalla El- Mowafy (JU):
aelmowafi@gmail.com
Dr. Mowafy bichm-1-Fop-JU 1
House-keeping rules ‫*)(م‬+‫ا‬
• Attendance.
• Cell phones off, please.
• Breaks and food. 50 minute
lecture
• Quite pls !
• Questions welcome
any time.
• Exams and evals: MCQ-
False/True. Little notes
Total pages-13 1
1- Quizzes (10) Marks

• Quiz-1,2 (week-3) (week-5)
5
• AB(C DE‫ر‬-:;<(=>+‫@? ا‬
• Quiz-3, 4 (week-10) (week-12)

5
• AB(C DE‫ر‬-:;<(=>+‫@? ا‬
2- Midterm 25
3- Final 40
4- Practical 25
• 20 Exam
Total: 100
• 5 (work-behavior-attendance ) = ‫ام‬GH+I‫ا‬

Dr. Abdalla El- Mowafy 2010 (JU)
What is biochemistry ?
= Chemistry of cells and organs
(biological systems)
• Is the chemistry/function of biomolecules in health and
disease:
- Carbohydrates: e.g. Glucose- Glycogen (Diabetes)

- Proteins: Enzymes- Hormones (metabolism- activity)
- Lipids: Cholesterol (How/when Good, or Bad ?)
- DNA: Genes (DNA: Characters- Diseases)
• Clinical Chemistry (application of biochemistry):

- Cholesterol level indicates risk of atherosclerosis RST‫;ا‬U+‫ ا‬VWXY
- CPK enzyme diagnoses myocardial infarction (heart attack)
- Glucose in blood diagnoses Diabetes mellitus ‫]\;ي‬+‫ا‬
Dr. Abdalla El- Mowafy 2010 JU)
Total pages-13 2
Biochemistry of the Living Cell

Cell Cycle:
Division, Cancer and Apoptosis
The Cell Cycle :ASW^+‫ ا‬:‫دور‬
• The life of a cell from its formation from

a dividing parent cell until its own
division
parent
cell
Dr. Mowafy bichm-1-Fop-JU
cell cycle 6
Total pages-13 3
why cells divide?

Roles of Cell Division *:
• Reproduction: ((T;H\d+‫; )ا‬c(\H+‫ا‬
– Cells divide to form two daughter cells.
• Growth: e>*+‫ا‬
– Embryonic cells grow and divide to form organism
• Repair (healing, replacement): ‫ل‬hiI‫ ا‬-‫(م‬fH+I‫ا‬

– Bone marrow stem cells grow and divide to give
rise to new blood cells. ‫م‬+,‫ ا‬./01 ‫ن‬345 6789,‫ع ا‬.;<,‫ ا‬./01
7
Mitotic cell cycle
• Various stages in cell cycle, aim to:
– Cells must grow (get ready for division).

– DNA (chromosomes) is replicated (duplicated)
– Chromosomes separate into 2 similar sets
– Cell divides into similar daughter cells
(cytokinesis)
Total pages-13 4
Cell cycle stages**

3Gs = ‫اد‬+9IJ‫ ا‬-EF‫را‬
S, M = ‫م‬.MNO‫ا‬
Abbre
State Phase Description
viation
A resting phase where the cell has left the cycle and has
Gap 0 G0
stopped dividing.
Cells increase in size. The G1 checkpoint ensures that
Gap 1 G1
Interphase everything is ready for DNA synthesis.
(most of Synth-
time) S DNA replication occurs.
esis
The cell continues to grow before mitosis. The G2 checkpoint

Gap 2 G2
ensures that everything is ready for the M (mitosis/division).
The cell divides into two daughter cells. A checkpoint in the
Metaphase
Mitosis M middle of mitosis (Metaphase Checkpoint) ensures that 9 the
1 hr
cell is ready to complete cell division. Dr. Mowafy bichm-1-Fop-JU
Cell cycle stages**

Go
~24 hours for typical
“Resting” human cell to divide
not actively
growing
or
dividing
variable length 10-12 hours

of time
4-6 hours
~1 hours for
mitotic phase
Total pages-13 5
What controls cell division ?
• Frequency of cell division

– Controlled by specific chemical signals
present in cytoplasm
• Cell-Cycle Control System
Mechanical Analogy for the Cell-Cycle

Control System: ASW^+‫ ا‬:‫ دور‬oS)*Y opq+ rS‫(آ‬t
G1 checkpoint
Checkpoints are
control points
Located at G1,
G1 S
G2, and M
“STOP” points in M G2
cell-cycle unless
overridden by
“GO” signals
M checkpoint G2 checkpoint
Total pages-13 6
Cell Cycle Control Molecules *
• Two main types of control molecules

–Protein kinases
–Cyclins
• Changes in the abundance and activity

of control molecules pace the cell
cycle.E^c;,‫م ا‬.MNO‫ع إ‬.N/‫ إ‬WXY/ .Z[.\O‫ و‬.ZI^7‫ آ‬6` a^b5
Cell - Cycle Control Molecules
• Kinases (Enzymes that add phosphate group on cell proteins)

– Cdks - cyclin-dependent kinases
– Phosphorylate other cell proteins
– Give the “GO” signals at G1 and G2 checkpoints
Example: first discovered Cdk was the MPF

• Maturation-promoting factor
• gives the “GO” signal at G2 checkpoint
Total pages-13 7
Mechanism of the cell-cycle control at the G2

checkpoint ( via MPF) **
1)- Cyclin increases

during G1, S, & G2
1
2)- It complexes with
Cdk at G2 to form
MPF
3) MPF allows
crossing the G2
checkpoint (M)
4
4) Cyclin is degraded
and Cdk is released
2
Dr. Mowafy bichm-1-Fop-JU 3 15
Characteristics of animal Cells in

Culture: how cancer cells differ *?
• Density-dependent inhibition 37<,‫ ا‬d‫ود‬+ef

– Cells grow and divide until they reach a
certain density, then they stop
• Anchorage dependence g^XhIc, ic‫ه‬

– Cells grow attached to a surface
• Culture flask or extracellular matrix
Total pages-13 8
Density-dependent inhibition: NORMAL Cells
Cells are anchored to dish and divide
Cells stop dividing when they form a

complete single layer (like healing)
If some cells are removed, cell growth

begins until the gap is filled
17
Density and anchorage regulations are

absent in cancer cells*
Cancer cells grow beyond a single layer forming a clump of

overlapping cells. Do not display anchorage dependence
multiple layers of cells
Total pages-13 9
Cancer Cells *
• No density-dependent inhibition
• No anchorage dependence (logic !).
• Immortal - continually divide
• Not under cell-cycle control

– may manufacture own GF
– may have mutation in signaling pathway
– may have mutation in cell cycle controls
Cancer Cells: carcinogenesis* ‫ن‬.[aM,‫ا‬
• Transformation (normal cell cancer cell)

– initiated by carcinogens (Chemicals/smoking) and
requires >1-2 mutations in certain-genes that
control cell division and/or apoptosis. This leads to
uncontrolled cell proliferation/growth (tumor):
– ”Benign“: cells remain at original site a^s1a^t- +^7F

– ”Malignant“: cells are invasive = (metastasis) u^X1.
They migrate to, harbor and disrupt other tissues
(liver- bone- lung- brain). 20
Total pages-13 10
Growth and metastasis of a

malignant breast tumor
A tumor grows from a single cancerous cell and may

invade neighboring tissues.
Growth and metastasis of a

malignant breast tumor
cancer cells spread through cancer cells may

lymph and blood vessels establish a new
to rest of the body tumor at a new
site in the body
Total pages-13 11
Programmed cell death (PCD)

(Apoptosis): role in health and disease
• Unlike necrosis (traumatic cell death ‫(دم‬XH+‫ل أو ا‬e{>+(E ‫|م‬p+‫)ا‬:

PCD Occurs in multicellular organisms
through certain biochemical signals that lead
to selective death of certain cells (keeping
others), and organized disposal of cellular
debris. rSt(*T|+‫|وزر أو زرع ا‬Wd+(E ‫|م‬p+‫ا‬
How apoptosis occurs* ?

• 1. Cell shrinks and gets rounded
(breakdown of the protein cytoskeleton
by caspases).
• 2. The cell membrane forms irregular

buds (blebs).
• 3. The cytoplasm becomes dense, and the

organelles get tightly packed.
• 4. Chromatin condenses into patches and

DNA gets fragmented.
• 5. The cell breaks into vesicles (apoptotic

bodies) which are then phagocytosed .
24
Total pages-13 12
Functions of apoptosis:
1) cell termination*
A) For development: removal of •
un-needed tissue. Differentiation
of fingers and toes in a
developing human embryo
occurs because cells between
the fingers apoptose; the result
is that the digits are separate. Embryonic foot of mouse-
developed foot
•
B) Removal of a damaged cell •

after virus infection, ionizing
radiation, toxic chemicals or
starvation.
Incomplete differentiation in two
toes due to lack of apoptosis
Functions of apoptosis:
2) Cell Homeostasis* (Th^+‫|د ا‬B
2) Cell Homeostasis: ‫(ء‬BI‫ @? ا‬A>SW]+‫( ا‬Th^+‫|د ا‬B ?WB ‫(ظ‬q=+‫ا‬
Homeostasis is achieved when the rate of mitosis (cell

division) in the tissue is balanced by cell death.
Disturbance of this equilibrium leads to serious
conditions (tumor OR cell loss/organ dysfunction).
In the adult organism, the number of cells is kept

relatively constant through cell death and division.
Cells must be replaced when they become diseased,
and proliferation must be offset by cell death.
• ‫ ا‬AfSU>E oY Dr. Mowafy bichm-1-Fop-JU 26
Total pages-13 13

Lecture 1 Biochem 232 Cells

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Verfügbare Formate

Biochem-232-DrMowafy-Pharmacy-JU 9/21/2010

Dr. Abdalla El- Mowafy (JU):

House-keeping rules ‫*)(م‬+‫ا‬

1- Quizzes (10) Marks

• Quiz-3, 4 (week-10) (week-12)

Dr. Mowafy bichm-1-Fop-JU 3

- Carbohydrates: e.g. Glucose- Glycogen (Diabetes)

• Clinical Chemistry (application of biochemistry):

Biochemistry of the Living Cell

Dr. Mowafy bichm-1-Fop-JU 5

The Cell Cycle :ASW^+‫ ا‬:‫دور‬

• The life of a cell from its formation from

why cells divide?

• Repair (healing, replacement): ‫ل‬hiI‫ ا‬-‫(م‬fH+I‫ا‬

Mitotic cell cycle

• Various stages in cell cycle, aim to:

– Cells must grow (get ready for division).

Dr. Mowafy bichm-1-Fop-JU 8

Cell cycle stages**

The cell continues to grow before mitosis. The G2 checkpoint

Cell cycle stages**

variable length 10-12 hours

Dr. Mowafy bichm-1-Fop-JU 10

What controls cell division ?

• Frequency of cell division

• Cell-Cycle Control System

Dr. Mowafy bichm-1-Fop-JU 11

Mechanical Analogy for the Cell-Cycle

Cell Cycle Control Molecules *

• Two main types of control molecules

• Changes in the abundance and activity

Cell - Cycle Control Molecules

• Kinases (Enzymes that add phosphate group on cell proteins)

Example: first discovered Cdk was the MPF

Mechanism of the cell-cycle control at the G2

1)- Cyclin increases

Characteristics of animal Cells in

• Density-dependent inhibition 37<,‫ ا‬d‫ود‬+ef

• Anchorage dependence g^XhIc, ic‫ه‬

Dr. Mowafy bichm-1-Fop-JU 16

Density-dependent inhibition: NORMAL Cells

Cells are anchored to dish and divide

Cells stop dividing when they form a

If some cells are removed, cell growth

Density and anchorage regulations are

Cancer cells grow beyond a single layer forming a clump of

multiple layers of cells

Dr. Mowafy bichm-1-Fop-JU 18

• Not under cell-cycle control

Cancer Cells: carcinogenesis* ‫ن‬.[aM,‫ا‬

• Transformation (normal cell cancer cell)

– ”Benign“: cells remain at original site a^s1a^t- +^7F

Growth and metastasis of a

A tumor grows from a single cancerous cell and may

Growth and metastasis of a

cancer cells spread through cancer cells may

Dr. Mowafy bichm-1-Fop-JU 22

Programmed cell death (PCD)

• Unlike necrosis (traumatic cell death ‫(دم‬XH+‫ل أو ا‬e{>+(E ‫|م‬p+‫)ا‬:

Dr. Mowafy bichm-1-Fop-JU 23

How apoptosis occurs* ?

• 2. The cell membrane forms irregular

• 3. The cytoplasm becomes dense, and the

2) Cell Homeostasis: ‫(ء‬BI‫ @? ا‬A>SW]+‫( ا‬Th^+‫|د ا‬B ?WB ‫(ظ‬q=+‫ا‬