Lecture 1 Biochem 232 Cells

8/8/2019 Lecture 1 Biochem 232 Cells

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

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1Dr. Mowafy bichm-1-Fop-JU

Dr. Abdalla El- Mowafy (JU):

[email protected]

Substate

Active site

Enzyme

Diabetic retinopathy

House-keeping rules

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



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Total: 100

1- Quizzes (10) Marks

Quiz-1,2 (week-3) (week-5)

- 5

Quiz-3, 4 (week-10) (week-12)

- 5

2- Midterm 25

3- Final 40

4- Practical

20 Exam

5 (work-behavior-attendance = (

25

3Dr. Mowafy bichm-1-Fop-JUDr. Abdalla El- Mowafy 2010 (JU)

What is biochemistry ?= Chemistry of cells and organs

(biological systems)

Is the chemistry/function of biomolecules in health anddisease:

- 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 - CPK enzyme diagnoses myocardial infarction (heart attack)- Glucose in blood diagnoses Diabetes mellitus

4Dr. Mowafy bichm-1-Fop-JUDr. Abdalla El- Mowafy 2010 JU)


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Biochemistry of the Living Cell

Cell Cycle:Division, Cancer and Apoptosis


The Cell Cycle :

The life of a cell from its formation froma dividing parent cell until its own

division

cell cycle

parentcell



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why cells divide?

Roles of Cell Division *: Reproduction: )(

Cells divide to form two daughter cells.

Growth: Embryonic cells grow and divide to form organism

Repair (healing, replacement): - Bone marrow stem cells grow and divide to give

rise to new blood cells. 7

Dr. Mowafy bichm-1-Fop-JU

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)

Mitotic cell cycle



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State PhaseAbbreviation

Description

Interphase

(most of

time)

Gap 0 G0A resting phase where the cell has left the cycle and hasstopped dividing.

Gap 1 G1Cells increase in size. The G1checkpointensures thateverything is ready for DNA synthesis.

Synth-esis S DNA replication occurs.

Gap 2 G2The cell continues to grow before mitosis. The G2checkpointensures that everything is ready for the M (mitosis/division).

Metaphase1 hr

Mitosis MThe cell divides into two daughter cells. A checkpoint in themiddle of mitosis (Metaphase Checkpoint) ensures that thecell is ready to complete cell division.

Cell cycle stages**

9


3Gs = -S, M =

Go

variable lengthof time

10-12 hours

4-6 hours

~24 hours for typicalhuman cell to divide

~1 hours formitotic phase

Cell cycle stages**


Restingnot activelygrowingordividing


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What controls cell division ?

Frequency of cell division

Controlled by specific chemical signalspresent in cytoplasm

Cell-Cycle Control System


Checkpoints arecontrol points

Located at G1,G2, and M

STOP points incell-cycle unlessoverridden byGO signals

Mechanical Analogy for the Cell-CycleControl System :

G1 checkpoint

G2 checkpointM checkpoint

G1

G2M

S



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Cell Cycle Control Molecules *

Two main types ofcontrol molecules

Protein kinases

Cyclins

Changes in the abundance and activityof control molecules pace the cellcycle.


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



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1)- Cyclin increasesduring G1, S, & G2

2)- It complexes withCdk at G2 to formMPF

3) MPF allows

crossing the G2checkpoint (M)

4) Cyclin is degradedand Cdk is released

4

1

Mechanism of the cell-cycle control at the G2checkpoint ( viaMPF) **

3

2


Characteristics of animal Cells inCulture: how cancer cells differ *?

Density-dependent inhibition Cells grow and divide until they reach a

certain density, then they stop

Anchorage dependence Cells grow attached to a surface

Culture flask or extracellular matrix



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Cells are anchored to dish and divide

Cells stop dividing when they form acomplete single layer (like healing)

If some cells are removed, cell growthbegins until the gap is filled

Density-dependent inhibition: NORMAL Cells


Density and anchorage regulations areabsent in cancer cells*

Cancer cells grow beyond a single layer forming a clump ofoverlapping cells. Do not display anchorage dependence

multiple layers of cells



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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*

Transformation (normal cell cancer cell)

initiated by carcinogens (Chemicals/smoking) and

requires >1-2 mutations in certain-genes thatcontrol cell division and/or apoptosis. This leads touncontrolled cell proliferation/growth (tumor):

Benign: cells remain at original site -

Malignant: cells are invasive = (metastasis) .They migrate to, harbor and disrupt other tissues(liver- bone- lung- brain). 20



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Growth and metastasis of amalignant breast tumor

A tumor grows from a single cancerous cell and mayinvade neighboring tissues.


Growth and metastasis of amalignant breast tumor

cancer cells spread throughlymph and blood vesselsto rest of the body

cancer cells mayestablish a newtumor at a newsite in the body



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Unlike necrosis (traumatic cell death ):

PCD Occurs in multicellular organisms

through certain biochemical signals that leadto selective death of certain cells (keepingothers), and organized disposal of cellulardebris.

Programmed cell death (PCD)

(Apoptosis): role in health and disease


How apoptosis occurs* ?

1. Cell shrinks and gets rounded(breakdown of the protein cytoskeletonby caspases).

2. The cell membrane forms irregularbuds (blebs).

3. The cytoplasm becomes dense, and theorganelles get tightly packed.

4. Chromatin condenses into patches andDNA gets fragmented.

5. The cell breaks into vesicles (apoptoticbodies) which are then phagocytosed .



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A) For development: removal ofun-needed tissue. Differentiationof fingers and toes in adeveloping human embryooccurs because cells betweenthe fingers apoptose; the resultis that the digits are separate.

B) Removal of a damaged cellafter virus infection, ionizingradiation, toxic chemicals orstarvation.

Functions of apoptosis:

1) cell termination*

Incomplete differentiation in twotoes due to lack of apoptosis

Embryonic foot of mouse-developed foot


2) Cell Homeostasis:

is achieved when the rate of mitosis (cellHomeostasis

division) in the tissue is balanced by cell death.Disturbance of this equilibrium leads to seriousconditions (tumor OR cell loss/organ dysfunction).

In the adult organism, the number of cells is keptrelatively constant through cell death and division.Cells must be replaced when they become diseased,and proliferation must be offset by cell death.

Functions of apoptosis:

2) Cell Homeostasis*


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Lecture 1 Biochem 232 Cells

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