Lipid Metabolism

Question 1

phospholipid structure

Answer 1

polar lipids with glycerol backbones and fatty acid tails (can be saturated or unsaturated); amphipathic nature (hydrophobic tails and hydrophilic backbone)

Question 2

triglyceride structure

Answer 2

neutral lipids (hydrophobic); this is how we package fat within adipocyte
-one glycerol bound to 3 fatty acids

Question 3

lipoproteins

Answer 3

spherical particles required for lipid transport between the tissues; polar lipids & apolipoproteins (activate enzymes) on the surface and hydrophobic tails pointed toward the core

Question 4

chylomicrons

Answer 4

the lipoproteins generated from dietary fats, made in the small intestine; require Apo B48

Question 5

what apolipoprotein is on chylomicrons

Answer 5

Apo B48 (also Apo C-II and Apo E)

Question 6

describe the role of lipoprotein lipase

Answer 6

lipoprotein lipase in the capillaries cleaves the triglycerides in the core of the chylomicrons, releasing free fatty acids and glycerol; activated by Apo C-II

Question 7

HDL (good cholesterol)

Answer 7

pulls cholesterol from the peripheral tissues and shuttles it to the liver to be excreted as bile salts or shut down cholesterol biosynthesis

Question 7

LDL (bad cholesterol)

Answer 7

takes cholesterol from the liver and transports it to the peripheral tissues; if we don’t have enough receptors, it can build up in the blood and cause hyperlipidemia

Question 8

apolipoprotein B48

Answer 8

gut; chylomicrons
-involved in release of chylomicrons from the enterocyte into lymphatic system (lacteals) and endocytosis of remnants

Question 8

apolipoprotein C-2

Answer 8

chylomicrons and VLDL
*lipoprotein lipase activation

Question 8

apolipoprotein B 100

Answer 8

liver; VLDL
-involved in release of VLDL from liver and endocytosis of remnants

Question 9

apolipoprotein E

Answer 9

receptor mediated endocytosis of remnants (after chewed up by lipoprotein lipase)

Question 10

apolipoprotein D

Answer 10

cholesterol ester transfer protein (CETP) of HDL

Question 11

apolipoprotein A-1

Answer 11

lecithin:cholesterol acyl transferase (LCAT) activation

Question 12

digestion and uptake of triglycerides into intestinal cells

Answer 12

1) triglycerides (TGs) are partially hydrolyzed by lingual and gastric lipases
2) TGs, some monoglycerides, fatty acids, and other dietary lipids associate with bile salts to form bile salt micelle
3) pancreatic lipase and co-lipase bind to the micelle and complete TG hydrolysis to free fatty acids and monosaccharides
4) micelle docks on intestinal villi; monosaccharides and fatty acids enter enterocyte
5) in enterocyte, monosaccharides and fatty acids put back together into TGs
6) triglycerides and phospholipids packaged into chylomicrons
7) chylomicrons need to acquire Apo B48 to be secreted into lacteals and then into blood

Question 13

purpose of carnitine shuttle

Answer 13

bring fatty acids across the inner mitochondrial membrane for beta-oxidation

Question 14

steps of carnitine shuttle

Answer 14

1) FFA from acyl-CoA is transferred to carnitine by the enzyme carnitine acyltransferase I (CAT-I) and enters the intermembrane space
2) carnitine-acyl-carnitine translocase brings the acyl-carnitine into the mitochondrial MATRIX
3) CAT-II transfers fatty acid back to CoA to form acyl-CoA in the matrix
4) carnitine shuttled back out to start cycle again; acyl-CoA used for beta oxidation

Question 15

fatty acid beta-oxidation

Answer 15

one round of beta-oxidation yields an acetyl-CoA and a fatty acid w/ 2 less carbons on it, along with 1 FADH2 and 1 NADH2, and acetyl-CoA enters the TCA cycle
-beta-oxidation keeps going until the entire fatty acid is oxidized

Question 16

net yield of ATP from beta-oxidation

Answer 16

106 ATP from a 16-C fatty acid
[108 made, 2 ATP used for activation]

Question 17

what is the only organ that can make ketone bodies

Answer 17

the liver (but it cannot use them)

Question 18

rate limiting enzyme in formation of ketone bodies

Answer 18

HMG CoA synthase

Question 19

rate limiting enzyme in formation of acetyl-CoA from ketone bodies

Answer 19

succinyl-CoA transferase

Question 20

which ketone body gets converted to acetyl-CoA

Answer 20

acetoacetate

Question 21

ingredients for making complex lipids

Answer 21

backbone, fatty acid, polar head group (to make a phospholipid)

Question 22

ATP citrate lyase

Answer 22

converts citrate to acetyl-CoA for fatty acid synthesis

Question 22

what is the rate-limiting enzyme for fatty acid synthesis

Answer 22

acetyl-CoA carboxylase

Question 23

acetyl-CoA carboxylase

Answer 23

RATE-LIMITING ENZYME OF FATTY ACID SYNTHESIS
converts acetyl-CoA to malonyl-CoA
*requires biotin and ATP to bind CO2
*activated by: citrate & insulin
*upregulates fatty acid synthase gene
*inhibited by glucagon

Question 24

fatty acid synthase

Answer 24

combines 7 malonyl-CoA with 1 acetyl-CoA to form a 16-C fatty acid
***requires 14 NADPH

Question 25

how does malonyl-CoA regulate fatty acid synthesis and beta-oxidation

Answer 25

-stimulates fatty acid synthesis
-inhibits carnitine shuttle (to shut down beta-oxidation)

Question 26

triglyceride synthesis in adipocytes

Answer 26

1) insulin promotes GLUT4 transporters on adipocytes, allowing glucose in (as glycerol-3-P)
2) lipoprotein lipase releases free fatty acids from chylomicrons
3) 3 fatty acids are linked to G-3-P to form a triglyceride
4) triglycerides form a globule, which acquires perilipin for storage

Question 27

triglyceride breakdown in adipocytes

Answer 27

1) glucagon binds its receptor, activating adenylyl cyclase, which increases cAMP levels, which activates PKA
2) PKA phosphorylates hormone-sensitive lipase
3) phosphorylated hormone-sensitive lipase hydrolyzes triglycerides into free fatty acids and glycerol

Question 28

hormone sensitive lipase

Answer 28

an enzyme involved in breakdown of triglycerides in the adipocytes; must be phosphorylated (by PKA) to be active

Question 29

prostaglandins

Answer 29

functions include vascular permeability, pain, and fever
-found in most cells

Question 30

thromboxanes functions

Answer 30

functions include vasoconstriction and platelet aggregation
-found in platelets and macrophages

Question 31

leukotrienes

Answer 31

functions include vasoconstriction, vascular permeability, leukocyte attraction, and inflammation
-found in inflammatory cells (neutrophils, macrophages, mast cells)

Question 32

lipoxins

Answer 32

terminate the inflammatory response
-found in inflammatory cells (neutrophils, macrophages, mast cells)

Question 33

what are the inflammatory mediators (eicosanoids)

Answer 33

-prostaglandins
-thromboxanes
-leukotrienes
-lipoxins (resolve inflammation)

Question 34

where do the inflammatory mediators (eicosanoids) originate from

Answer 34

they all come from arachidonic acid

Question 35

phospholipase A2

Answer 35

an enzyme that hydrolyzes fatty acids from the 2nd carbon of a phospholipid to form arachidonic acid
*requires calcium

Question 36

what are the precursors for arachidonic acid

Answer 36

1) linoleic acid (omega 6)
2) linolenic acid (omega 3)

Question 37

how are eiconasoids made from arachidonic acid

Answer 37

cyclooxygenases (COX 1 and COX 2)

Question 38

how does aspirin work as a therapeutic drug

Answer 38

aspirin acetylates a serine residue in the active site of COX 1 and COX 2, acting as an irreversible inhibitor
-this prevents thromboxane synthesis
-results in less platelet aggregation and less thrombus formation

Question 39

what is the rate-limiting enzyme of cholesterol synthesis

Answer 39

HMG CoA reductase

Question 40

steps of cholesterol synthesis

Answer 40

acetate -> mevalonate -> activated isoprene -> squalene -> cholesterol

Question 41

how do statins work

Answer 41

statins inhibit (competitive inhibitor) HMG CoA reductase, the rate-limiting enzyme for cholesterol synthesis

Question 42

receptor basis of familial hypercholesterolemia

Answer 42

LDL receptor mutations (many different types of mutations but most mutations reside in the LDL-binding domain of the receptor)