Lipid Metabolism

Question 1

Types of lipids

Answer 1

• triglycerides (main one)
• phosopholipids
• cholesterol

Question 2

Fatty acids

Answer 2

Basic moiety of all lipids

- long chain hydrocarbon organic acids

Question 3

Lipid functions

Answer 3

Triglycerides are used primarily for energy production (similar to CHO)

• composition: 3 fatty acids and 1 glycerol
• cholesterol and phospholipids used to make cell membranes

Question 4

Lipoproteins

Answer 4

Carrier service for lipids in the plasma

• transport lipids to and from liver
• transport lipids to other tissues for use/storage
• made of cholesterol, triglycerides, phospholipids, and protein

Question 5

Types of lipoproteins

Answer 5

• chylomicrons: carry digested fat from intestines to lymphatics (most relevant)
• low density lipoproteins: contains higher cholesterol
• very low density lipoproteins: high triglycerides/moderate cholesterol
• high density lipoproteins: contains lower cholesterol

Question 6

Bile formation

Answer 6

Bile is made by hepatocytes at rate of 1/2 - 1 liter/day
- stored in gallbladder
Functions
- fat digestion
- excretion of wastes, including cholesterol and bilirubin

Question 7

Bile composition

Answer 7

Bile salts make up 50% of composition
- bile salts made from cholesterol –> cholic acid or chenodeoxycholic acid –> conjugation with taurine or glycine –> conjugated bile acids

Question 8

Role of bile salts

Answer 8

Bile released from gallbladder when fat reaches duodenum

• contraction stimulated by cholecystokinin
• bile salts emulsify fat globules and then form micelles that allow further digestion/absorption of fats
• bile salts are left behind in GIT lumen and recycled back to liver for repeat use

Question 9

Cholecystokinin via blood stream causes

Answer 9

• gallbladder contraction

- relaxation of sphincter of Oddi

Question 10

Where is bile stored?

Answer 10

Gallbladder

- concentrated up to 15 times

Question 11

What does secretin in the bloodstream do?

Answer 11

Stimulates liver ductal secretion

- Na and HCO3 added via secretin hormone to prevent bile from being too acidic

Question 12

Step 1 of lipid digestion

Answer 12

Bile salts break down fat globules (mostly TG) into smaller sizes (emulsification) so lipase enzymes can act on them

Question 13

Step 2 of lipid digestion

Answer 13

Bile salts form micelles

• micelles allow water soluble enzymes to act further on fat for digestion
• shuttle broken down fats (free fatty acids) to the intestinal brush border and release them into the intestinal cells
• free fatty acids shuttled to smooth ER of cell and new TG are packaged into chylomicrons –> released from base of cell into thoracic duct OR FFA are absorbed directly into blood from GIT

Question 14

What is the biggest component of a chylomicron?

Answer 14

Triglycerides

Question 15

Chylomicrons

Answer 15

Type of lipoprotein, mostly triglycerides

• increase in serum after a meal, causing turbidiy or whitish color, while they carry TG in the bloodstream
• are cleared within 30 minutes in normal animals

Question 16

Primary hypertriglyceridemia in dogs

Answer 16

Breed predisposition
- schnauzers
- shetland sheepdogs
Diagnosis
- elevated FASTING triglycerides
Consequences
- pancreatitis
- poor glucose regulation in diabetics
- ocular problems

Question 17

Fate of triglycerides in the blood: option 1

Answer 17

Taken up by liver
- TG split into free FA –> oxidation of FA to supply ATP for body functions OR synthesis of cholesterol, phospholipids, and most lipoproteins

Question 18

_____ of cholesterol made in liver is converted to bile salts

Answer 18

80%

- remainder is transported in lipoproteins in the blood to needy tissues

Question 19

Phospholipids made in liver

Answer 19

Transported by lipoproteins

• cell membrane formation
• intracellular structure formation/reactions
• second messenger systems

Question 20

Fate of TG in the blood: option 2

Answer 20

Used by other tissues for energy or storage

• especially adipose, heart, and muscle
• taken up via lipoprotein lipase (LPL) found in walls of capillaries
• chylomicron –> LPL –> TG and phospholipids –> free FA + glycerol (lipolysis)
• left over chylomicron is cholesterol rich and gets cleared by liver

Question 21

Free FA is used for

Answer 21

• energy via beta oxidation, Kreb’s cycle, and oxidative phosphorylation
• storage of fat
• production of new TG or other lipids

Question 22

Lipolysis

Answer 22

TG hydrolyzed to FA + glycerol

• glycerol enters cells –> glycolysis
• FA goes to needy tissues –> further processing

Question 23

Lipolysis step 2

Answer 23

Fatty acids shuttled to mitochondria

• FA moved to mitochondria for degradation and oxidation
• amino acid carnitine acts as an enzyme to assist in this movement

Question 24

Lipolysis step 3

Answer 24

Beta oxidation of fatty acids yields acetyl CoA

- yields 4 H+

Question 25

Lipolysis step 4

Answer 25

Acetyl CoA enters TCA cycle | - products (per acetyl CoA): 2 CO2, 8 H+, 1 ATP

Question 26

Lipolysis step 5

Answer 26

Oxidative phosphorylation of >100 H+ atoms from previous steps - yields more than >100 ATP

Question 27

When would the body make more fatty acids?

Answer 27

- if body can't use carbs (diabetes) - in starvation - to store excess carbs and protein

Question 28

Synthesis of fatty acids from excess carbs and protein

Answer 28

Necessary if CHO or protein are in excess and no more glycogen can be formed - storage of fat provides a log of energy back up - fat is more energy dense than carbs - 1st step is conversion of glucose or AA to acetyl CoA

Question 29

Synthesis of fat from proteins and CHO occurs in the ____

Answer 29

Liver

Question 30

Lipid storage

Answer 30

Adipose tissue's major function is storage of TG until needed by liver or other tissues - adipocytes are 80-90% stored fat - TG stored inside cell in liquid form - lipases are activated once this stored fat is needed by the rest of the body

Question 31

Tapping into lipid stores

Answer 31

When cells need energy, hormone sensitive lipase can signal release of stored fat from adipose - stored fat --> hormone sensitive lipase --> free FA in blood --> binds albumin --> tissue in need

Question 32

Free FA concentration is significantly increased in absence of ____

Answer 32

Carbs or inability to use carbs | - ex: diabetes mellitus

Question 33

What happens if lipid concentrations are too elevated?

Answer 33

Liver degrades excess fatty acids into keto-acids (ketones) - FA --> acetyl CoA --> ketones --> cells --> acetyl CoA --> TCA cycle - FA --> acetyl CoA --> ketones --> ketoacidosis (in a state of no carb metabolism)

Question 34

Diabetic ketoacidosis

Answer 34

Accumulation of ketones is common in sick or poorly controlled diabetics - due to insufficient insulin or insulin resistance - causes illness, acidosis, vomiting/diarrhea, lethargy, inappetence

Question 35

Hormonal control over lipid metabolism

Answer 35

Insulin-decreased CHO utilization and fat storage, increased fat mobilization (free FA) for energy - thyroxine-rapid mobilization of fat to release free FA

Question 36

What activates hormone sensitive lipase and releases free FA for energy

Answer 36

- epinephrine - glucocorticoids - growth hormone

Question 37

What signals satiety to the hypothalamus?

Answer 37

Leptin - produced by full adipocytes - released into bloodstream ---> hypothalamus - decreases fat storage - decreases appetite

Question 38

Fat soluble vitamins

Answer 38

- A: stored as retinol, needed for retinal development, epithelial health, reproduction - D: increases calcium and phosphorous absorption from GIT and bone - E: antioxidant - K: necessary cofactor for activates (carboxylates) clotting factors 2, 7, 9, and 10