Lecture 9- Lipids Metabolism

Question 1

Lipid Metabolism After a Meal:

Answer 1

• CHO, protein, fat enter blood stream after being absorbed in the small intestine, then enter hepatocyte (liver cell)
• Lipids enter through chlymicron remnants (CR)- most dropped off at adipose and muscle tissue, but left over lipids are brought back and cleared in the liver through CR
○ Fatty acids enter pool to create TAG
○ Phospholipids and cholesterol can be packaged with Apoproteins to create VLDL and HDL
○ Can be cleared out (biliary excretion)
• Glucose is packaged as glycogen or enters glycolysis, Kreb’s cycle
○ Form glycerol-3-phosphate during glycolysis (backbone for producing TAGs
○ Can be used to synthesize TAG within the hepatocyte
Amino acids can form oxaloacetate and enter Kreb’s cycle

Diagram + Diagram

Question 2

Integrated Metabolism of Fat and CHO:

Answer 2

• Gluconeogenesis- glycerol backbone is glucogenic, can be used to generate glucose (backbone is used for gluconeogenesis- NOT the fatty acids themselves)
Kreb’s Cycle- fat oxidation via acetyl CoA (how fatty acids release all their energy through breakdown)

Question 3

Lipolysis and Gluconeogenesis:

Answer 3

• Lipases hydrolyze ester linkages (lipolysis) in TAG (seen in intestine for absorption and for energy use in the body)
• In adipose tissue, HSL (hormone sensitive lipase) cleaves a fatty acid from the glycerol backbone
○ Inhibited by insulin
○ Insulin is high right after a meal (don’t need to break down fat for energy)
Breakdown of 1 TAG molecule releases 1 glycerol and 3 fatty acids

Diagram

Question 4

Beta Oxidation and Kreb’s Cycle:

Answer 4

• Removes 2 carbons at a time per pass
		• 4 step process
			○ Dehydrogenation
			○ Hydration
			○ Oxidation
			○ Thiolysis
		• Each round produces an acetyl CoA, fatty acid that is shorter by 2 carbons, 1 FADH2, 1 NADH
			○ Acetyl CoA enters Kreb's cycle
FADH2 and NADH goes to ETC

Pathway

Question 5

Dietary Cholesterol:

Answer 5

• For healthy people, limiting dietary cholesterol does not change blood cholesterol much
  * For 10-25% of those with high cholesterol, decreasing dietary cholesterol will decrease LDL
  * Plant sterols compete with cholesterol for uptake by NPC1L1 into the intestine, but plant sterols are then pumped back into the lumen by ABCG5/G8 (enters cells, but not blood)

Diagram

Question 6

Trans Fatty Acids:

Answer 6

• Unsaturated fatty acids with at least one double bond in trans configuration
• Industrial trans fats are produced during the hydrogenation of vegetable oils
○ Increase stability during cooking, longer shelf life, palatability
○ Hydrogen atoms are added catalytically across double bonds
§ Partial hydrogenation results in the remaining double bonds being converted from cis to trans
§ Complete hydrogenation results in a saturated fatty acid
○ Increased amounts of hydrogenation increases the degree of saturation
• Industrial trans fats will be completely banned in Canada in 2018
• Also found naturally in ruminant fat
○ Milk fat contains 4-8% trans fat (conjugated linoleic acid- CLA)
Natural trans fats are made in the rumen through bacterial fermentation

Question 7

Trans Fats and Cardiovascular Disease Risk:

Answer 7

• High intake of industrial trans fatty acids leads to
○ Increases LDL- increases cholesterol
○ Increases total cholesterol
○ Increases inflammation
○ Decreases HDL- increases cholesterol
• Linked to CVD
• Trans fats appear to increase the risk of CHD more than any other nutrient (on a per calorie basis)
Impact of natural trans fats on CVD risk is equivocal in scientific literature

Question 8

Integrated Metabolism of Fat and CHO:

Answer 8

• Gluconeogenesis- glycerol backbone is glucogenic

Kreb’s Cycle- fat oxidation via acetyl CoA