Lipid Metabolism Flashcards
phospholipid structure
polar lipids with glycerol backbones and fatty acid tails (can be saturated or unsaturated); amphipathic nature (hydrophobic tails and hydrophilic backbone)
triglyceride structure
neutral lipids (hydrophobic); this is how we package fat within adipocyte
-one glycerol bound to 3 fatty acids
lipoproteins
spherical particles required for lipid transport between the tissues; polar lipids & apolipoproteins (activate enzymes) on the surface and hydrophobic tails pointed toward the core
chylomicrons
the lipoproteins generated from dietary fats, made in the small intestine; require Apo B48
what apolipoprotein is on chylomicrons
Apo B48 (also Apo C-II and Apo E)
describe the role of lipoprotein lipase
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
HDL (good cholesterol)
pulls cholesterol from the peripheral tissues and shuttles it to the liver to be excreted as bile salts or shut down cholesterol biosynthesis
LDL (bad cholesterol)
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
apolipoprotein B48
gut; chylomicrons
-involved in release of chylomicrons from the enterocyte into lymphatic system (lacteals) and endocytosis of remnants
apolipoprotein C-2
chylomicrons and VLDL
*lipoprotein lipase activation
apolipoprotein B 100
liver; VLDL
-involved in release of VLDL from liver and endocytosis of remnants
apolipoprotein E
receptor mediated endocytosis of remnants (after chewed up by lipoprotein lipase)
apolipoprotein D
cholesterol ester transfer protein (CETP) of HDL
apolipoprotein A-1
lecithin:cholesterol acyl transferase (LCAT) activation
digestion and uptake of triglycerides into intestinal cells
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
purpose of carnitine shuttle
bring fatty acids across the inner mitochondrial membrane for beta-oxidation
steps of carnitine shuttle
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
fatty acid beta-oxidation
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
net yield of ATP from beta-oxidation
106 ATP from a 16-C fatty acid
[108 made, 2 ATP used for activation]
what is the only organ that can make ketone bodies
the liver (but it cannot use them)
rate limiting enzyme in formation of ketone bodies
HMG CoA synthase
rate limiting enzyme in formation of acetyl-CoA from ketone bodies
succinyl-CoA transferase
which ketone body gets converted to acetyl-CoA
acetoacetate
ingredients for making complex lipids
backbone, fatty acid, polar head group (to make a phospholipid)
ATP citrate lyase
converts citrate to acetyl-CoA for fatty acid synthesis
what is the rate-limiting enzyme for fatty acid synthesis
acetyl-CoA carboxylase
acetyl-CoA carboxylase
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
fatty acid synthase
combines 7 malonyl-CoA with 1 acetyl-CoA to form a 16-C fatty acid
***requires 14 NADPH
how does malonyl-CoA regulate fatty acid synthesis and beta-oxidation
-stimulates fatty acid synthesis
-inhibits carnitine shuttle (to shut down beta-oxidation)
triglyceride synthesis in adipocytes
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
triglyceride breakdown in adipocytes
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
hormone sensitive lipase
an enzyme involved in breakdown of triglycerides in the adipocytes; must be phosphorylated (by PKA) to be active
prostaglandins
functions include vascular permeability, pain, and fever
-found in most cells
thromboxanes functions
functions include vasoconstriction and platelet aggregation
-found in platelets and macrophages
leukotrienes
functions include vasoconstriction, vascular permeability, leukocyte attraction, and inflammation
-found in inflammatory cells (neutrophils, macrophages, mast cells)
lipoxins
terminate the inflammatory response
-found in inflammatory cells (neutrophils, macrophages, mast cells)
what are the inflammatory mediators (eicosanoids)
-prostaglandins
-thromboxanes
-leukotrienes
-lipoxins (resolve inflammation)
where do the inflammatory mediators (eicosanoids) originate from
they all come from arachidonic acid
phospholipase A2
an enzyme that hydrolyzes fatty acids from the 2nd carbon of a phospholipid to form arachidonic acid
*requires calcium
what are the precursors for arachidonic acid
1) linoleic acid (omega 6)
2) linolenic acid (omega 3)
how are eiconasoids made from arachidonic acid
cyclooxygenases (COX 1 and COX 2)
how does aspirin work as a therapeutic drug
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
what is the rate-limiting enzyme of cholesterol synthesis
HMG CoA reductase
steps of cholesterol synthesis
acetate -> mevalonate -> activated isoprene -> squalene -> cholesterol
how do statins work
statins inhibit (competitive inhibitor) HMG CoA reductase, the rate-limiting enzyme for cholesterol synthesis
receptor basis of familial hypercholesterolemia
LDL receptor mutations (many different types of mutations but most mutations reside in the LDL-binding domain of the receptor)
