Lipid metabolism

Question 1

triglycerides

Answer 1

-triglycerides are storage molecules for lipids
-water insoluble
- no risk of undesired breakage

Question 2

triglyceride transport

Answer 2

• ingested triglycerides need a protein carrier to travel through the blood, to make them overall water soluble

Question 3

triglyceride breakdown

Answer 3

• uses coenzyme A to breakdown triglycerides to be used for fuel
• beta-oxidation

Question 4

how are fatty acid fuels obtained (3 ways)

Answer 4

1. fats consumed in diet
2. fats stored in cells as lipid droplets
3. synthesis of fats by the liver

Question 5

bile salts definition

Answer 5

• synthesized molecules from cholesterol in the liver, stored in the gallbladder, and released into the small intestine after ingestion of fatty meal

Question 6

bile salts role in triglyceride breakdown

Answer 6

• solubilizes triglycerides by creating a mixed micelle of bile salts and triacylglycerol (aka triglyceride)
• aids in lipid breakdown/ and absorption of digested products

Question 7

what happens after bile salts interaction?

Answer 7

• micelle is able to interact with water-soluble pancreatic lipase in the intestine
• which breaks triglycerides to smaller pieces (mono/diglycerides, free FA)
• these products dissolve into intestinal mucosa and are then reconverted into triacylglycerol packaged into chylomicrons in the ER

Question 8

chylomicron structure

Answer 8

• triacylglycerol in the center, with protein, phospholipids and cholesterol on the outside

Question 9

what is an apolipoprotein

Answer 9

lipid-binding protein in the blood

Question 10

what is a lipoprotein

Answer 10

combination of a lipid and an apolipoprotein

Question 11

what is a chylomicron

Answer 11

• largest type of lipoprotein and least dense
• it’s synthesized in the epithelial cells of the small intestine, and transported via lymphatic tissue into the bloodstream
• delivers dietary triglycerides to various tissue

Question 12

what important apolipoprotein does chylomicrons contain and what do they do?

Answer 12

ApoC-II, important because it activate lipoprotein lipase which allows triglycerides to breakdown into FA’s in tissues

Question 13

what happens to chylomicron remnants after chylomicrons are broken down?

Answer 13

Re-circulated into the liver, cholesterol is released and remainder is degraded into lysosomes in the hepatocytes

Question 14

VLDL (very low-density lipoproteins)

Answer 14

• happens when intake of FA’s is more than what’s need immediately for fuel:
• then is converted to triacylglycerol in the liver and packaged as VLDL
• transported to muscle for energy or adipose tissue for storage of lipid droplets

Question 15

LPL (lipoprotein lipase)

Answer 15

enzyme that breaks down chylomicrons and VLDL from triglycerides to FA’s, different function based on tissue
- cardiac and skeletal muscle: provides energy
- adipose tissue: stimulates triacylglycerol storage

Question 16

LPL in high vs low insulin levels

Answer 16

• high insulin: increase of LPL in adipose tissue = fuel storage
• low insulin: increase LPL activity in muscle tissue, release FA’s from VLDL for fuel

Question 17

IDL (intermediate-density lipoprotein)

Answer 17

• these are equivalent to VLDL remnants
• either are removed from the bloodstream by the liver or a precursor for LDL’s

Question 18

LDL (low-density lipoproteins)

Answer 18

-uses apolipoprotein ApoB-100 to transport to target tissue
- transports cholesterol to tissues, cholesterol uptake into extrahepatic tissues

Question 19

HDL (high-density lipoprotein)

Answer 19

• contains enzyme cholesterol acyl transferase (LCAT)
• catalyzes the formation of cholesteryl esters
• extract cholesterol from chylomicrons and VLDL remnants

Question 20

why is HDL transportation unique

Answer 20

it’s reversal cholesterol transport, which means it picks up cholesterol in the tissues and carries it to the liver

Question 21

what organ is capable of disposing of significant amounts of cholesterol

Answer 21

the liver

Question 22

Acyl-CoA: cholesterol acyltransferase (ACAT)

Answer 22

esterifies free cholesterol by linking it to a fatty acid, preparing it for storage in liver cells or packaging into lipoproteins

Question 23

LDL - lipid transport

Answer 23

• distribution and delivery of cholesterol to peripheral tissues is mediated by binding of LDL to LDL receptors on plasma membrane of target cells

Question 24

LDL receptors relation to high intracellular cholesterol

Answer 24

• high intracellular cholesterol reduces LDL receptors and therefore reduces its own synthesis by inhibiting enzymes HMG-CoA reductase/synthase

Question 25

LDL receptors relation to high LDL

Answer 25

- high LDL in the plasma correlates to atherosclerosis, because it saturates LDL receptors. Then, it enters via a nonspecific endocytic process leading to excessive cholesterol uptake

Question 26

what does "bulk-phase pinocytosis" refer to?

Answer 26

unregulated uptake of cholesterol because of excess LDL

Question 27

Beta-oxidation pathway

Answer 27

series of enzyme catalyzed rxns that degrade FA's by removing 2-carbon units from the carboxyl end - takes place in the mito matrix

Question 28

1st part of Beta-oxidation pathway

Answer 28

free FA's need to be activated, which occurs by the enzyme fatty acyl-CoA synthetase. Turns free FA's into fatty acyl-CoA - occurs in the cytoplasm, requires ATP

Question 29

beta-oxidation pathway if FA chain is large

Answer 29

fatty acyl-CoA changes carriers from CoA to carnitine in the IMS, so that it can move into the mito matrix. - changes back to CoA in the mito matrix

Question 30

beta-oxidation overview

Answer 30

highly exergonic, purpose it to generate energy through the break down of FA's, needs 2 ATP results in: - 1 NADH - 1 FADH2 - 1 acetyl-CoA and 1 fatty acyl-CoA

Question 31

what can the product of beta-oxidation (acetyl-CoA) be used for?

Answer 31

the citric acid cycle or becomes a ketone body

Question 32

ketone bodies use

Answer 32

important metabolic fuel for many peripheral tissues - such as, heart and skeletal muscle, or the brain (uses ketone bodies as fuel in starvation)

Question 33

ketosis

Answer 33

a condition in which ketone bodies are produced faster than metabolized, leads to ketoacidosis (lowered blood pH)

Question 34

FA biosynthesis

Answer 34

- occurs through condensation of C2 units, opposite of beta-oxidation (different pathway though) - mainly in the liver and adipose tissue - takes place in cytoplasm, endergonic process

Question 35

requirements for FA biosnythesis

Answer 35

each round requires: - an activated malonyl-CoA (1 ATP per round for activation) - 2 NADPH

Question 36

regulation of FA metabolism

Answer 36

- glucagon, epinephrine, and norepinephrine stimulate cAMP, which stimulates PKA (phosphorylation)= active beta-oxidation and inhibited FA biosynthesis - insulin decreases cAMP, activates acetyl-CoA carboxylase (dephosphorylation) = active FA biosynthesis, inhibits beta-oxidation

Question 37

AMPK on FA metabolism

Answer 37

- activated by AMP and inhibited by ATP - promotes catabolic process and inhibits anabolic ones (so activates glycolysis and FA oxidation, inhibits FA synthesis)