Metabolism - Lecture Twenty-Five

Question 1

Where do bile acids (bile salts) solubilise fat?

Answer 1

In the gastrointestinal tract

Question 2

Synthesis of bile salts

Answer 2

Bile salts are synthesised from cholesterol in the liver and stored in the gall bladder as bile

Question 3

Secretion of bile salts

Answer 3

The secretion of bile salts are in proportional to the amount of lipid and are secreted into the small intestine in response to cholecystokinin

Question 4

Bile salts (in terms of detergents)

Answer 4

are powerful detergents with hydrophobic and hydrophilic surfaces

Question 5

Bile salts (in terms of digestion)

Answer 5

form micelles with triacylglycerols to increase surface area for digestion

Question 6

What does bile contain?

Answer 6

Water, bile acids, electrolytes, phospholipids, cholesterol and bile pigments

Question 7

Increase in cholesterol

Answer 7

results in gall stones

Question 8

Three examples given for regulation of digestion by polypeptide hormones

Answer 8

Gastrin, secretin and cholecystrokinin

Question 9

Gastrin source

Answer 9

Stomach

Question 10

Secretin source

Answer 10

Duodenum

Question 11

Cholecystokinin source

Answer 11

Duodenum

Question 12

Gastrin major stimulus for production

Answer 12

Protein-containing food in the stomach and also para-sympathetic nerves to stomach

Question 13

Secretin major stimulus for production

Answer 13

HCl in duodenum

Question 14

Cholecystokinin major stimulus for production

Answer 14

Fats and amino acids in the duodenum

Question 15

Gastrin major actions

Answer 15

Stimulates secretion of gastric juices

Question 16

Secretin major actions

Answer 16

Stimulates secretion of alkaline bile and pancreatic fluids

Question 17

Cholecystokinin major actions

Answer 17

Stimulates release of pancreatic enzymes and stimulates release of bile from gallbladder

Question 18

How are lipids emulsified?

Answer 18

By bile salts to form micelles (complex lips and protein structures)

Question 19

What does the pancreatic lipase/co-lipase enzyme system bind to?

Answer 19

Lipid/aqueous interface of micelle and hydrolyses triacylglycerols

Question 20

What do pancreatic lipase hydrolyse?

Answer 20

Fatty acids at positions 1 and 3 of glycerol backbone of triacylglycerol to form smaller micelles

Question 21

What do small micelles contain?

Answer 21

Bile salts, free fatty acids, monoacylglycerol (and cholesterol)

Question 22

Where a micelles absorbed?

Answer 22

Across the intestinal cell membrane

Question 23

What does pancreatic lipase hydrolyses triacylglycerols into?

Answer 23

Free fatty acids and 2-monoacylglycerol

Question 24

Fat malabsorption

Answer 24

leads to excess fat and fat soluble vitamins in faeces

Question 25

How is fat malabsorption caused?

Answer 25

By conditions that interfere with bile or pancreatic lipase secretion, ie. pancreatitis, gall bladder or liver diseases

Question 26

Example given of fat malabsorption

Answer 26

Orlistat

Question 27

Orlistat

Answer 27

Makes a covalent linkage with a side chain near the co-lipase active site which forms a stable complex that blocks the active site of the lipase resulting in no hydrolysis of tracylglycerol and not available as free fatty acids

Question 28

Lipoproteins

Answer 28

Help ‘solubilise’ lipids for transport in blood to tissues and provide a ‘delivery system’ for transporting lipids into and out of cells

Question 29

Important functions of apoproteins

Answer 29

structural for assembly (apoB) and ligands for cell surface receptors (apoE and apoB) - enzyme cofactors (apoCII for lipoprotein lipase)

Question 30

Four main lipoprotein classes

Answer 30

Chylomicrons, VLDL, LDL and HDL

Question 31

Two major lipid transport pathways

Answer 31

Exogneous chylomicron pathway and endogenous VLDL/LDL pathway

Question 32

Exogneous chylomicron pathway

Answer 32

Dietary fat

Question 33

Endogenous VLDL/LDL pathway

Answer 33

Endogenously synthesised fat

Question 34

Chylomicron assembly

Answer 34

Triacylglycerols and other lipids combine with apoB in the ER to form chylomicrons. Chylomicrons secreted from intestinal epithelial cells enter the bloodstream via the lymphatic system.

Question 35

Chylomicrons

Answer 35

Can give plasma a ‘milky’ appearance after a fat-rich meal

Question 36

Lipoprotein lipase enzyme location

Answer 36

Found on the endothelial surface

Question 37

What does the lipoprotein lipase do?

Answer 37

Hydrolyses TAG in lipoproteins to glycerol and fatty acids highest activities in heart and skeletal muscle and adipose tissue

Question 38

What is the lipoprotein lipase activated by?

Answer 38

ApoCll

Question 39

Defects (by mutation) in either apoCII or lipoprotein lipase

Answer 39

Lead to elevated levels of chylomicrons and plasma triacylglycerol

Question 40

Familial hypercholesterolmia (FH)

Answer 40

Common form of hyperlipidaemia which leads to premature atherosclerosis and is a dominant disorder

Question 41

How is familial hypercholesterolmia caused?

Answer 41

By defect in LDL receptor gene (many different mutations)

Question 42

LDL levels in familial hypercholesterolmia

Answer 42

2-3x higher than normal

Question 43

How is familial hypercholesterolmia treated?

Answer 43

With ‘statins’ to lower LDL and increase HDL (‘good’ cholesterol)

Question 44

Treatment for patients with high blood triglyceride levels?

Answer 44

Tricor (fenofibrate)