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71 Cards in this Set

  • Front
  • Back
What is the defining characteristic of lipids?
property of being hydrophobic
What do most lipids contain or are derived from?
fatty acids (FAs)
Nearly all mammalian FAs have an odd or even number of carbon atoms?
even
What are the number of carbon atoms and the sites of unsaturation in myristic acid?
14:0
What are the number of carbon atoms and the sites of unsaturation in palmitic acid?
16:0
What are the number of carbon atoms and the sites of unsaturation in palmitoleic acid?
16:1(9)
What are the number of carbon atoms and the sites of unsaturation in stearic acid?
18:0
What are the number of carbon atoms and the sites of unsaturation in oleic acid?
18:1(9)
What are the number of carbon atoms and the sites of unsaturation in linoleic acid?
18:2(9,12)
What are the number of carbon atoms and the sites of unsaturation in linolenic acid?
18:3(9,12,15)
What are the number of carbon atoms and the sites of unsaturation in arachidonic acid?
20:4(5,8,11,14)
What is the precursor of prostaglandins and other eicosanoids?
Arachidonic acid
What is the configuration of natural double bonds?
cis-configuration
How are trans fattyacids introduced to the body?
through the diet
How are fatty acids stored?
as esters of glycerol (acylglycerols)
What is the most common form of glycerol?
Tag - triacylglycerol - when all 3 hydroxyl groups of glycerol are esterified. Tags have FA attached to three different positions (all three FAs not need be the same type)
What is the most common TAG?
Oleic acid 18:1(9)
What is the advantage of storing energy as TAG vs glycogen?
TAGs pack together hydrophobicly excluding water.

Glycogen binds twice its weight in water.

TAGs yield 2.5 times as much ATP upon oxidation compared to glycogen.

Average person stores ~ 350 g glycogen in liver and muscle. This is ~ 1400 kilocalories (less than one days energy).

Average person stores ~ 10 kilograms TAG which is enough energy to survive several weeks.

Glycogen storage is limited.

TAG storage is unlimited. Adipocytes expand to keep accommodating more TAGs.
What happens to TAGs in the diet?
they are digested in the stomach and small intestine by gastric and pancreatic lipases to 2-monoacylglycerols and free FAs
Where are free fatty acids and 2-monoacylglycerols absorbed?
epithelial cells of small intestine
What does the liver do with excess carbohydrates and amino acids?
converts them to free fatty acids and TAGs
What is a chylomicron?
tag rich plasma lipoprotein
What is VLDL?
very low density lipoprotein (filled with tags)
What happens to TAGs circulating as chylomicrons and VLDLs in the blood stream when they come in contact with capillary endothelial cells of adipose tissue and skeletal muscle?
they are hydrolyzed by lipoprotein lipase that is located on the capillary endothelial cells
What happens to the fat droplets of TAGs that allows them to be saved for a fasted state?
They are coated with a protein called perilipin
How are TAGs released from the protein coat perilipin to be used in a fasted state?
they have to be phosphorylated (additional in adipocytes is the enzyme hormone sensitive lipase which also must be phosphorylated to be active and release TAGS)
When and how are perilipin and hormone sensitive lipase phosphorylated and thus activated?
When the hormone insulin goes low and glucagon goes high, glucagon activates the pathway to yeild cAMP dependent protein kinase A which phosphorylates the lipase and perilipin
What do free FA bind to in the serum>?
albumin which carries them through the bloodstream
What is transported to the liver and used in gluconeogenesis?
glycerol
How long does it take to go into ketosis?
greater than 2 days of fasting and the liver start converting FAs to ketones
How does obesity contribute to insulin resistance?
Obese individuals have elevated levels of FFAs in the bloodstream. The increased metabolism of FFAs decreases use of glc and glycogen. FA utilization blocks the insulin-stimulated transport of glc into muscle cells by blocking GLUT4 recruitment to the cell surface. Pancreatic b-cells fail under prolonged overproduction of insulin resulting in Type 2 diabetes.
What is the synthesis of fatty acids called?
lipogenesis
What happens to excess glucose and amino acids?
they are converted to acetyl coa and nadph which are used to synthesize palmitic acid
Where do all other FAs other than palmitic acid come from?
modifications to palmitic acid
Why are all FA chains synthesized in humans even numbered?
they are synthesized 2 carbons at a timme from acetyl coa and thus even in number
What are the enzymes used to synthesize palmitic acid?
just fatty acid synthase - a multienzyme complex
What is the rate limiting step in FA synthesis?
activation of acetyl Coa to malonyl coa
What is the reaction for the change of acetyl coa to malonyl Coa?
CO2 from bicarb is linked to acetyl coa carboxylase using atp energy. The CO2 is then transfered to acetyl Coa
How does fatty acid elognation occur?
Fatty acid synthase contains a phosphopantetheine moiety (PhP) which mediates acyl transfer and is derived from the vitamin pantothenic acid.

An acetyl group from acetyl-CoA is transferred to the PhP priming the rxn.

The acetyl group is transferred to another cys on fatty acid synthase to free the PhP.
Malonyl-CoA is added to the primed fatty acid synthase.

The CO2 from bicarbonate is released.

NADPH supplies the electrons for reduction.

All the carbon atoms in palmitic acid come from the acetyl groups.

Rxns 1 through 5 are repeated until palmitic acid is synthesized (16:0).
How does the fatty acid synthase know when to terminate elongation?
A thioesterase on fatty acid synthase recognizes the FA when it reaches a length of 16 carbons and releases the FFa
Where does glycolysis occur?
cytosol
Where does pyruvate from glycolysis go after glycolysis?
crosses into mt where it is converted to acetyl coa
Can acetyl coa cross the mt membrane?
no
Where does fatty acid synthesis occur?
cytosol
How does the FA synthesis in the cytosol occur if the acetyl coa is in the mt?
Citrate cleavage pathway. A tricarboxylic acid transporter moves citrate to the cytosol where ATP-citrate lyase cleaves citrate into acetyl coa and oaa
How is citrate formed from pyruvate in the mt matrix?
Pyruvate carboxylase converts pyruvate to Oxaloacetate while pyruvate dehydrogenase complex converts pyruvate to acetyl coa. Together they form citrate via citrate synthase.
What is the first reaction of beta-oxidation?
The enzyme acyl-CoA dehydrogenase is a flavoprotein that uses FAD as an electron acceptor to oxidize the acyl-CoA to a trans-desaturated at the 2-carbon-enoyl-CoA.

FADH2 will later donate these electrons to the oxidative phosphorylation pathway.
What is the second reaction of beta-oxidation?
Enoyl-CoA hydratase adds water (hydration) to remove the double bond forming 3-L-hydoxyacyl-CoA.
What is the third reaction of beta oxidation?
) In rxn 3 the enzyme 3-L-hydroxyacyl-CoA dehydrogenase oxidizes the b hydroxyl to a b ketone while reducing NAD+ to NADH.

NADH electrons can go to the oxidative phosphorylation pathway.
What is the fourth reaction of beta oxidation?
In the final step of b-oxidation, b-ketoacyl-CoA thiolase cleaves acetyl-CoA and attaches the two carbon shorter fatty acyl to another CoA.

Acetyl-CoA goes to the TCA cycle.

The shorter fatty acyl-CoA undergoes another b-oxidation until it is entirely acetyl-CoA.
Where does cholesterol come from?
Diet and synthesized from acetyl-coa in virtually all cells, particularly greatest in liver, intestine, adrenal cortex, and reproductive tissues
What is the structure of cholesterol?
contains four fused rings (A, B, C, D), a hydroxyl group at C3 of ring A, a double bond in ring B, an attached 8-member hydrocarbon chain on ring D, and two methyl groups
What is the structure of lipoproteins?
lipids in the core (Tags and cholesterol) with an outer shell of apolipoproteins and phospholipids
How are lipoproteins classified?
by their density - as the lipid core gets smaller, the outer shell makes up more of the lipoproteins mass and it becomes more dense
How much plasma cholesterol is free (unesterified)?
30%
How much plasma cholesterol is esterified at c3 to a long chain fatty acid?
70%
What happens to TAGs when they are absorbed by the small intestine?
They are packed into chylomicrons. Chylomicrons rich in both TAG and cholesterol receive ApoC-II from HDL then bind to skeletal muscle and adipose tissue endothelium.

ApoC-II activates lipoprotein lipase (LPL) which cleaves the TAGs for use by the cells.

The cholesterol rich chylomicron remnants (CR) reenter circulation and are taken up by the liver. CR binds to a remnant receptor on the liver’s surface.

CR is engulfed using receptor-mediated endocytosis.

An LDL-receptor similarly mediates LDL being engulfed.

The receptors are recycled to the hepatocyte’s surface while CR and LDL are digested by fusion of the endosome with lysosomes.
The liver synthesizes VLDL as necessary based on cholesterol and FA needs.

The main purpose of VLDL is to transport FAs and Cholesterol out to peripheral tissues.
What is HDL a reservoir for?
ApoE and ApoC-II, transfers these apolipoproteins to VLDL. ApoC-II activates LPL which releases FAs forming IDL and LDL.

Peripheral cells needing cholesterol and FAs express LDL receptors to endocytose the LDL.
What is the main purpose of HDL?
) is to transport excess cholesterol from peripheral cells to the liver (reverse cholesterol transport).
Where is HDL made?
the liver
What transfers free cholesterol and phospholipids from peripheral cell membranes to nascent HDL?
ATP-Binding Cassette Transporter (ABCA-1)
What is the purpose of LCAT or lecithin:cholesterol acyl transferase enzyme?
transfers the FA from position 2 of phosphatidylcholine (aka lecithin) to the 3-hydroxyl of cholesterol. Some of the choleseryl esters (CE) formed by LCAT are transferred to VLDL by cholesterol ester transfer protein (CETP).
What is the function of Phospholipid transfer protein (PLTP)?
Transfers phospholipids to VLDLs
What happens to HDL with unused CEs and TAGs?
Returns to the liver where hepatic lipase hydrolyzes TAGs
What is the function of scavenger receptor BI?
removes cholesterol esters
Where is HDL degraded?
liver
Where is arachidonic acid stored?
cell membranes; it is an essential fatty acid
What is required to form thromboxanes, series 2 prostaglandins, and leukotrienes?
arachidonic acid
What releases arachidonic acid from cell membranes?
phospholipase A2
What is the difference between series 1 and series 2 prostagladins?
Series 2 are omega 6 fatty acids derived from arachidonic acid and are inflammatory. Series 1 are omega-6 fatty acids derived from gamma-linolenic acid and are anti-inflammatory
Where are thromboxanes produced and what do they cause?
Produced in thrombocytes and cause platelet aggregation