Louis StodieckPhone: 492-4010

E-mail: stodieck@colorado.eduOffice: ECAE 113

Lecture Notes Website

www.colorado.edu\ASEN\asen5426

Reading AssignmentsDate Lecture Assignment

4/1 Cellular growth, division, differentiation and death

Guyton Ch. 2 & 3Lodish Ch. 13, p495-500, p:524-533

4/3 Cellular responses to external signals Guyton Ch. 74Lodish Ch 20, p:848-862, p:884-894

4/8 Breakdown of cellular growth control: Cancer

Guyton Ch. 3Lodish Ch. 24, p1054-1069, p1076-1082

4/10 Insulin control of blood glucose Guyton Ch. 78Lodish Ch. 20, p:897-898

4/15 Calcium regulation and hormonal control of bone mass

Guyton Ch. 79Class Notes

4/17 Cellular mechanisms and local control of bone mass

Class Notes

4/22 Control of skeletal muscle mass Guyton Ch. 6, p:77-78 (10th ed), p:82-83 (11th ed); Ch. 84, p:968-973 (10th ed), p:1055-1061 (11th ed), Class Notes

4/24 Effects of novel environments on physiological controls

Guyton Ch. 43,

Class Notes

4/29 Applications in cell and tissue engineering Class Notes

5/1 Oral presentations

5/3 Exam III (During final exam slot – 4:30pm)

“Molecular Cell Biology”, Lodish, Berk, Zipursky, Matsudaira, Baltimore and Darnell, 2000.

Control via Cells and Tissues

• Controls emanate from cell form and function– 10-100 trillion cells in the human body– Each cell carries a full blueprint (genome)

but runs different subroutines (gene expression)

– Integrated responses of cell aggregates (tissues and organs) give rise to whole organism responses

Constituents of Cells

• Water (70-80%)

• Ions (Na+, K+, Ca2+, PO4-, Cl-, etc.)

• Carbohydrates (sugars, starches)

• Proteins (chains of amino acids)– Structural vs. enzymatic– Soluble vs. membrane bound

• Lipids (membranes, energy)

• Nucleic acids (DNA, RNA)

Intestine – Epithelial cells

Trachea –Epithelial cells

Pancreas –Acinar cells

Kidney – Podocytes

Adipose cells

Blood – Erythrocytes

Muscle fiber

Nerve fiber – Schwann cell

• Human DNA has 3.2 billion base pairs• Data is equivalent to ~800 Mbytes

– Only ~1.5% (12 Mb) codes for actual “products”

• Each cell (with few exceptions) contain 23 chromosome pairs

• Stretched out, DNA would be 6 ft. long for a single cell

• End to end, an individual’s DNA would reach to the sun and back 60 times!!!!

Human Genome

• Human genome has been sequenced– Humans have ~25,000 genes

• Yeast = 6,000 genes• Fruit fly = 13,000 genes• Nematode = 18,000 genes• Arabidopsis = 26,000 genes

– We differ from each other by roughly 1 base pair per 1000 (99.9% the same)

More Gene Trivia

Protein Synthesis a.k.a Translation

Comparison of Mammalian vs. Yeast Gene Structure

From: Hammond et al., 2000, Physiological Genomics, 3:163-173.

• Why is control necessary– Unchecked growth would be disastrous

• 1 cell = 4.2(10)-9 g• Assume cells divide once each day • N = 2t (N = number of cells, t = time in days)• In 1 month = 4.5 g• In 2 months = 4,800,000 Kg = 5,000 tons

– But cell division is necessary• Developmental growth• Maintenance of tissue and organ functions• Repair of damaged tissues• Immune cell proliferation

Control of Cell Division

Mitosis – cell division~30 min. to complete

Prep for mitosis~4-5 hours-DNA repair and “proofreading” DNA replication

~10 hours

Prep for DNA replicationHighly variable ~9 hrs. in cycling cells

Postmitotic cellsQuiescent phase

• Controlled by cyclin-dependent kinases (Cdks)

• Cdks are made through transcriptional induction– Growth factors– Hormones– Tissue disaggregation– Mitogens

Control of Cell Division

• Cdks phosphorylate proteins (RB) that would otherwise inhibit cell cycling

• Phosphorylation causes short-term positive feedback – Threshold response (not unlike action potential)

• Other proteins can delay or stop process or redirect cell to apoptosis

G1 Checkpoint

Apoptosis

• Cells commit suicide through programmed cell death

• Cells require trophic factors to prevent– Mechanism always armed– Binding of trophic factors alters phosphorylation– E.g., nerve growth factor (NGF)

• Final death agents are caspases (proteases)