Lecture 3

Front 1

What are the functions of cholesterol?

Back 1

1. part of cell membrane structure (fluidity)
2. precursor to steroid hormones
3. constituent of bile acids
4. important in vitamin D synthesis

Front 2

How is cholesterol synthesized in the liver?

Back 2

Hepatocytes in the liver generate cholesterol. Energy producing molecules (glucose/fatty acids) > acetyl CoA > hydromethylglutaryl CoA > mevolonate > cholesterol

Front 3

What is the rate-limiting enzyme that determines cholesterol synthesis in the liver?

Back 3

hydromethylglutaryl CoA reductase

Front 4

How is cholesterol synthesis upregulated?

Back 4

1. saturated fat increase
2. elevated insulin levels
3. trans fatty acids

Front 5

Why do saturated fatty acids increase cholesterol synthesis?

Back 5

Saturated fatty acids are a precursor to cholesterol production (reagent in cholesterol production process)

Front 6

Why do elevated insulin levels lead to increased cholesterol synthesis?

Back 6

Insulin is a hormone that is anti-lipolytic, meaning that it works against the breakdown of fat. Working against fat breakdown means that fat is preserved and stored. Fat is a precursor to cholesterol by turning into acetyl CoA and to HMG-CoA by HMG-CoA R and to mevolonate and then finally to cholesterol

Front 7

Why do trans fatty acids lead to increased cholesterol synthesis?

Back 7

Trans fatty acids are unsaturated synthetic fatty acids that act as saturated fat. It leads to cholesterol synthesis in the same way that saturated fat is a precursor to cholesterol synthesis.

Front 8

Why are type II diabetes patients obese?

Back 8

High insulin levels in patients, meaning that fat is not being broken down; fat is being stored and used as a precursor to cholesterol production

Front 9

How can cholesterol synthesis be limited?

Back 9

1. Decrease the amount of reactants (fatty acids, energy producing molecules)
2. Inhibit the enzyme (rate-limiting enzyme)

Front 10

Where is bile produced?

Back 10

liver

Front 11

How is bile produced?

Back 11

Using cholesterol as a constituent

Front 12

Why is bile necessary?

Back 12

Lipase cannot break down fat globules due to lack of surface area. Bile emulsifies fats to generate smaller droplets so that lipase can break down fats

Front 13

What is the purpose of lipase? Why can't lipase operate without bile?

Back 13

Lipase digests fats (fat breakdown) which are often lipid aggregates. Lipase cannot access the inside of lipid droplets if they are aggregated, so bile is necessary to break down or emulsify fat globules into smaller droplets. Emulsification increases the surface area of the fat, making it available for lipase digestion.

Front 14

How much bile is reabsorbed?

Back 14

95%

Front 15

How can the rate of bile excretion be increased?

Back 15

Water soluble substance (fiber) that binds to fiber and prevents recycling

Front 16

What is a lipoprotein disorder?

Back 16

a disorder in which abnormal levels of lipoproteins exist

Front 17

What is one example of lipoprotein disorder?

Back 17

familial hypercholesterolemia; unable to remove LDL from the blood; rare 100% genetic disease in which liver cells lack LDL receptors; causes higher risk of CVD; variable expressivity codominance

Front 18

How do cells receive cholesterol?

Back 18

Via LDL endocytosis; process is called receptor-mediated endocytosis...... binding to receptor must occur

Front 19

Homozygous and heterozygous familial hypercholesterolemia

Back 19

More than 600mg/dl cholesterol - severe //// 300-400 mg/dl, half LDL receptors compared to normal; 1/500 people have disease; manageable through diet

Front 20

What is statin?

Back 20

Drug that lowers cholesterol levels by inhibiting HMG-CoA reductase

Front 21

T/F The vast majority of individuals with high cholesterol have the genetic defect

Back 21

False - they have a genetic predisposition and it is a matter of a lifestyle disease

Front 22

How can cholesterol be managed?

Back 22

1. decrease intake of saturated fat and trans fatty acid to decrease cholesterol synthesis
2. increase water soluble fiber intake to promote excretion of bile (containing cholesterol)

Front 23

What kind of fiber is good?

Back 23

water soluble fiber

Front 24

What is the dietary cholesterol recommendation?

Back 24

American Heart Association: <<300mg/day

Front 25

What is the typical American diet?

Back 25

300-400 mg/day

Front 26

How does diet affect cholesterol?

Back 26

Cholesterol can be elevated by diet. Diet has the greatest impact on cholesterol levels. Diet can stimulate the liver and other tissues to produce cholesterol.

Diet can inhibit the production of LDL receptors.

Front 27

What do trans fatty acids do?

Back 27

unsaturated synthetic fatty acids that behave like saturated fatty acids (cis is natural)

increase LDL and decrease HDL

found in processed foods

Front 28

What happens with dietary cholesterol?

Back 28

Ends up in bloodstream and increases plasma cholesterol

Front 29

What is the benefit of water soluble fiber?

Back 29

1. forces body to excrete more bile
2. cholesterol is converted to bile
3. more LDL receptors produced in liver cells and cholesterol is taken up from the blood

Front 30

Describe the structure of the lipoprotein

Back 30

size: 10nm-1500nm but classified by density

Consists of a hydrophilic shell and hydrophobic core (amphipathic)

Contains cholesterol, triglyceride, phospholipids, apolipoproteins

Front 31

Which lipoprotein (VLDL, IDL, VLDL, HDL) is implicated in atherosclerosis?

Back 31

LDL - low density lipoprotein

Front 32

What is the ratio of importance that helps characterize CVD risk?

Back 32

LDL/HDL ratio

Front 33

What are chylomicrons?

Back 33

Made in enterocytes (epithelial cells in small intestine) to transfer dietary triglycerides to liver and tissues

Front 34

What is VLDL?

Back 34

Made in liver to transfer endogenous and stored lipids to body tissues (very low density lipoprotein)

Front 35

What is LDL?

Back 35

Formed in the blood from VLDL; continues to transport cholesterol to body tissues (low density lipoprotein)

Front 36

What is HDL?

Back 36

Made in the liver to transfer cholesterol from the blood back to the liver (high density lipoprotein)

Liver lacks cholesterol and HDL is sent to blood vessels to collect cholesterol

Front 37

What is the significance of density in lipoproteins?

Back 37

Less density means more fat (VLDL is first one out of the liver cholesterol warehouse - at this point it has the most fat until it eventually gets to LDL which is more dense and has less fat) inverse relationship between density and fat

Front 38

What is the recommended cholesterol level by the AHA?

Back 38

desirable: total <200mg/dl; LDL <130mg/dl

borderline: total <200-230mg/dl; LDL <130-159mg/dl

high risk: total >240mg/dl; LDL >160 mg/dl

Front 39

Key numbers for total cholesterol and LDL (recommendations by AHA)

Back 39

200 and 240 for total cholesterol
130 and 160 for LDL

Front 40

How does blood cholesterol level relate to CHD death?

Back 40

An increase in blood cholesterol level corresponds to an increase in CHD death

Front 41

Name the major risk factors for CVD

Back 41

1. physical inactivity
2. high fat or high caloric diet
3. smoking
4. inflammation
5. hypertension
6. insulin resistance
7. obesity
8. chronic stress
9. dyslipidemia

Front 42

What is the mnemonic device?

Back 42

Hipdocs

HHIIPDOCS