Cholesterol Cholesterols A sterol steroid

Cholesterol

Cholesterols • A sterol (steroid + alcohol) • Found in tissues with densely packed membranes: Liver, Spine, Brain • Most is synthesized internally

What does cholesterol do for us? • Maintains the viscosity of membranes – Not to loose, not too rigid • Aids in making bile which helps digest fats, including fat soluable vitamins, A, D, E, & K • Precursor to hormones • Note: In asia bear bile is a folk medicine • ~400 bears are “milked” for the bile in Hannoi

How do we make cholesterol? • We make about 1 gram a day – We eat ~. 2/. 3 g/day • Co. A: precursor • HMG-Co. A reductase – First enzyme – Made on 5 th chromosome

Acetyl Coenzyme A • Coenzymes: carry chemicals between enzymes • Co. A is in citric acid cycle making ATP – Also regulating fatty acid metabolism

Good vs. Bad Cholesterol • High Density lipoproteins: (size 8 -11 nm small) carry fats from tissues to liver – high concentrations of HDL (over 60 mg/d. L) lower risk for strokes & heart attackes – Men usually have less than women – Exercise, lose weight, stop smoking, diet = more HDL

Low Density Lipoprotein – Bad cholesterol • (18 -25 nm in diameter) • Carries cholesterol away from cells making it to cells using it – Also takes it to the arteries = artherosclerosis • better to have a few large LDL molecules than lots of little LDL molecules • Tracking this has more statistical predictive power than other heart disease correlates; smoking, diabetes, obesity

GIGO: Garbage in Garbage out • 1. LDL is the body's cholesterol-delivery service. It carries "packages" of cholesterol to the blood vessels and deposits them there for processing. 2. If you have too much cholesterol, it doesn't get processed. It just piles up in the blood vessels. 3. Meanwhile, HDL acts as a garbage truck in the blood vessels. It picks up the unprocessed cholesterol packages and takes them to the liver to be disposed of. 4. The more HDL there is, the more cholesterol can be cleared away. 5. If there's too little HDL and too much LDL, there will be a lot of "garbage" cholesterol.

Statins • HMG-Co. A reductase competitive inhibitors – Substrate can’t bind because this is in the active site – Stops first step of cholesterol synthesis

Bayer • Bayer’s has a Cholesterol lowering statin drug, Baycol (Cerivastatin). • Side effect: rhabdomyolysis – Skeleto-muscular breakdown leading to renal failure from all the junk in the blood stream • 385 reported cases, 52 deaths on top of that • 2001 Bayer took it off the market

Lipitor • One synthetic example: Atorvastatin (Lipitor) – 2005: 12. 2 billion in sales largest selling legal drug in the world – 10, 20, 40 or 80 mg tablets – Side effects include Myalgia (muscle pain), headache, insomnia, dizziness • 74. 8 million Lipitor prescriptions were dispensed in the U. S. two years ago more than 8, 500 per hour

Who makes lipitor? • Pfizer – NY company – World’s largest pharmaceutical company • Mass-produced penicillin for WWII • 1980’s Zoloft • 1990’s Viagra – 1 of 30 companies making up Dow Jones industrial average

• On June 26, 2006, Pfizer announced that it would sell its Consumer Healthcare unit (famous for wellknown brands like Listerine, Nicorette, Visine, Sudafed and Neosporin) to Johnson & Johnson for $16. 6 B

Never ask why you have to learn this. • Pfizer's 2004 R&D budget was $7. 7 billion -nearly as much as the combined budgets of Intel and HP • There are 38, 000 Pfizer sales reps worldwide -the equivalent of about three U. S. Army divisions • Pfizer's annual advertising budget is $3 billion -the fourth-largest in the U. S. as of 2003

Henry Mc. Kinnell • CEO of Pfizer from 2001 – recently • He made Pfizer merge with some other big companies. • Cost Pfizer money to do this • 1999 -2005 shares went from 50 -30$ – There’s 7 billion shares on the maket – How much money was lost? – 140 billion • base salary in 2005 of $2, 270, 500, and a bonus of $3, 700, 000. He also received $145, 814 in other compensation (primarily tax payments made by Pfizer on behalf of employees), and nearly $5. 5 million in long-term incentive payouts. • Donates to the republican party • He’s not the CEO anymore

Who did Pfizer pick to be the new CEO? • Choices – Karen Katen Veteran Head of commericial team – Jeff Kindler Relatively new Top lawyer – David Shedlarz Veteran Head financer • Veteran expected • Lawyer picked: reflects increasing legal nature of the business.

Who’s on the Dow Jones? • • • • 3 M Co. (NYSE: MMM) (conglomerates, "manufacturing") ALCOA Inc. (NYSE: AA) (aluminum) Altria Group, Inc. (NYSE: MO) (tobacco, foods) American International Group, Inc. (NYSE: AIG) (property & casualty insurance) American Express Co. (NYSE: AXP) (credit services) AT&T Inc. (NYSE: T) (telecoms) Boeing Co. , The (NYSE: BA) (aerospace/defense) Caterpillar, Inc. (NYSE: CAT) (farm & construction equipment) Citigroup, Inc. (NYSE: C) (money center banks) Coca-Cola Co. (NYSE: KO) (beverages) E. I. du Pont de Nemours & Co. (NYSE: DD) (chemicals) Exxon Mobil Corp. (NYSE: XOM) (major integrated oil & gas) General Electric Co. (NYSE: GE) (conglomerates, media) General Motors Corporation (NYSE: GM) (auto manufacturers) Hewlett-Packard Co. (NYSE: HPQ) (diversified computer systems) • • • • Home Depot, Inc. (NYSE: HD) (home improvement stores) Honeywell International, Inc. (NYSE: HON) (conglomerates) Intel Corp. (NASDAQ: INTC) (semiconductors) International Business Machines Corp. (NYSE: IBM) (diversified computer systems) JPMorgan Chase and Co. (NYSE: JPM) (money center banks) Johnson & Johnson Inc. (NYSE: JNJ) (consumer and health care products conglomerate) Mc. Donald's Corp. (NYSE: MCD) (restaurant franchise) Merck & Co. , Inc. (NYSE: MRK) (drug manufacturers) Microsoft Corp. (NASDAQ: MSFT) (software) Pfizer, Inc. (NYSE: PFE) (drug manufacturers) Procter & Gamble Co. (NYSE: PG) (consumer goods) United Technologies Corp. (NYSE: UTX) (conglomerates) Verizon Communications (NYSE: VZ) (telecoms) Wal-Mart Stores, Inc. (NYSE: WMT) (discount, variety stores) Walt Disney Co. , The (NYSE: DIS) (entertainment)