Chapter 20 Flashcards
… are hydrophobic lipids consisting of glycerol triesters of fatty acids such as palmitic and oleic acids
triacylglycerols
since triacylglycerols are water insoluble, whereas digestive enzymes are water soluble, triacylglycerol digestion takes place at … The rate of triacylglycerol digestion therefore depends on the … of the interface, which is greatly increased by the churning peristaltic movements of the intestine combined with the emulsifying action of …
lipid-water interfaces; surface area; bile acids
The … (also called …) are amphipathic detergent-like molecules that act to solubilize fat globules by dispersing them into micelles. Bile acids are cholesterol derivatives that are synthesized by the liver and secreted as glycine or taurine conjugates (Fig. 20-1) into the gallbladder for storage
bile acids; bile salts
Pancreatic lipase (triacylglycerol lipase) catalyzes the hydrolysis of triacylglycerols at their 1 and 3 positions to form sequentially … and … together with the Na+ and K+ salts of fatty acids (…). The enzymatic activity of pancreatic lipase greatly increases when it contacts the lipid–water interface, a phenomenon known as …
1,2-diacylglycerols; 2-acylglycerols; soaps; interfacial activation.
Binding to the lipid–water interface requires mixed micelles of phosphatidylcholine and bile acids, as well as pancreatic
…, a 90-residue protein that forms a 1:1 complex with lipase.
colipase
The mixture of fatty acids and mono- and diacylglycerols produced by lipid digestion is absorbed by the cells lining the small intestine (the…). Bile acids not only aid lipid digestion; they are essential for the …
intestinal mucosa; absorption of the digestion products
The micelles formed by the bile acids take up the nonpolar lipid degradation products so as to permit their transport across the unstirred aqueous boundary layer at the …
intestinal wall
Bile acids are likewise required for the efficient intestinal absorption of the …
lipid-soluble vitamins A, D, E, and K.
Inside the intestinal cells, fatty acids form complexes with…, a cytoplasmic protein that increases the effective solubility of the water-insoluble substances and also protects the cell from their detergent-like effects
intestinal fatty acid–binding protein (I-FABP)
….are globular micelle-like particles that consist of a nonpolar core of triacylglycerols and cholesteryl esters surrounded by an amphiphilic coating of protein, phospholipid, and cholesterol.
Lipoproteins
Intestinal mucosal cells convert dietary fatty acids to triacylglycerols and package them, along with dietary cholesterol, into lipoproteins called …. These particles are released into the intestinal lymph and are transported through the lymphatic vessels before draining into the large veins
chylomicrons
The bloodstream then delivers chylomicrons throughout the body. Other lipoproteins known as … (VLDL), …(IDL), and …(LDL) are synthesized by the liver to transport endogenous (internally produced) triacylglycerols and cholesterol from the liver to the tissues. … (HDL) transport cholesterol and other lipids from the tissues back to the liver.
very low density lipoproteins; intermediate density lipoproteins; low density lipoproteins; High density lipoproteins
the HDL, which are the most …of the lipoproteins, are also the
dense; smallest
The protein components of lipoproteins are known as …or just …
apolipoproteins; apoproteins
the helices in apolipoproteins have …and …side chains on opposite sides of the helical cylinder, suggesting that lipoprotein α helices are …and fl oat on phospholipid surfaces, much like logs on water.
hydrophilic; hydrophobic; amphipathic
Chylomicrons adhere to binding sites on the inner surface (endothelium) of the capillaries in skeletal muscle and adipose tissue. The chylomicron’s component triacylglycerols are hydrolyzed through the action of the extracellular enzyme… The tissues then take up the liberated monoacylglycerol and fatty acids
lipoprotein lipase
The chylomicrons shrink as their triacylglycerols are p rogressively hydrolyzed until they are reduced to cholesterol
enriched …
chylomicron remnants
Chylomicrons therefore deliver dietary triacylglycerols to …and …tissue, and dietary …to the liver
muscle; adipose; cholesterol
Very low density lipoproteins (VLDL), which transport endogenous triacylglycerols and cholesterol, are degraded by lipoprotein lipase in the capillaries of adipose tissue and muscle. The released fatty acids are taken up by cells and oxidized for …or used to … The glycerol backbone of triacylglycerols is transported to the liver or kidneys and converted to the glycolytic intermediate …
energy; resynthesize triacylglycerols; dihydroxyacetone phosphate
the VLDL remnants, which have also lost some of their apolipoproteins, appear in the circulation first as …and then as …. About half of the VLDL, after degradation to IDL and LDL, are taken up by the liver.
IDL; LDL
Animal cells acquire cholesterol, an essential component of cell membranes either by synthesizing it or by …, which are rich in cholesterol and cholesteryl esters. The latter process occurs by …(engulfment
taking up LDL; receptor-mediated endocytosis
The LDL particles are sequestered by LDL receptors, cell-surface transmembrane glycoproteins that specifically bind apoB-100. LDL receptors cluster into …which gather the cell-surface receptors that are destined for endocytosis while excluding other cell-surface proteins. The coated pits invaginate from the plasma membrane to form …
clathrin-coated pits; clathrin-coated vesicles
, after divesting themselves of their clathrin coats, the vesicles fuse with vesicles known as …, whose internal pH is ~5.0. Under these conditions, the LDL particle dissociates from its receptor
endosomes
… is a general mechanism whereby cells take up large molecules, each through a corresponding specifi c receptor
Receptor-mediated endocytosis
HDL have essentially the opposite function of LDL: They …from the tissues
remove cholesterol
A circulating HDL particle acquires its cholesterol by extracting it from …
cell-surface membranes.
The …is the only organ capable of disposing of significant quantities of cholesterol
liver
liver cells take up HDL by an entirely diff erent mechanism: Rather than being engulfed and degraded, an HDL particle binds to a cell-surface receptor named …(for scavenger receptor class B type I) and selectively transfers its … to the cell. The lipiddepleted HDL particle then dissociates from the cell and re-enters the circulation
SR-BI; component lipids
The triacylglycerols stored in adipocytes are mobilized in times of metabolic need by the action of … (Section 20-5). The free fatty acids are released into the bloodstream, where they bind to …
hormone-sensitive lipase; serum albumin
fatty acids are progressively degraded by… units and that the process involves the oxidation of the carbon atom β to the carboxyl group. This process is called …
two-carbon; 𝛃 oxidation
Before fatty acids can be oxidized, they must be “primed” for reaction in an ATP dependent acylation reaction to form fatty acyl-CoA. The activation process is catalyzed by a family of at least three ….(also called thiokinases) that differ in their chain-length specificities.
acyl-CoA synthetases
A long-chain fatty acyl-CoA cannot directly cross the inner mitochondrial membrane. Instead, its acyl portion is fi rst transferred to …, a compound that occurs in both plant and animal tissues.
carnitine
…which can transfer a variety of acyl groups are located, respectively, on the external and internal surfaces of the inner mitochondrial membrane. The translocation process itself is mediated by a specific carrier protein that transports …into the mitochondrion while transporting free carnitine in the opposite direction.
Carnitine palmitoyl transferases I and II; acyl-carnitine
The degradation of fatty acyl-CoA via β oxidation occurs in four reactions:
1. Formation of a trans-α,β double bond through dehydrogenation by the flavoenzyme … (AD).
- Hydration of the double bond by … (EH) to form a …
acyl-CoA dehydrogenase; enoyl-CoA hydratase; 3-L-hydroxyacyl-CoA.
The degradation of fatty acyl-CoA via β oxidation occurs in four reactions:
- NAD+-dependent dehydrogenation of the β-hydroxyacyl-CoA by …(HAD) to form the corresponding β-ketoacyl-CoA.
- Cα—Cβ cleavage in a thiolysis reaction with CoA as catalyzed by… (KT; also called just thiolase) to form acetyl-CoA and a new acyl-CoA containing two fewer C atoms than the original one.
3-Lhydroxyacyl-CoA dehydrogenase; 𝛃-ketoacyl CoA thiolase
the rxn catalyzed by acyl-CoA dehyrogenases is thought to involve removal of a ..at Cα and transfer of a hydride ion equivalent from Cβ to …
proton; FAD
…transfers an electron pair from FADH2 to the flavo-iron–sulfur protein ETF:ubiquinone oxidoreductase, which in turn transfers an electron pair to the mitochondrial electron- transport chain by reducing coenzyme Q. Reduction of O2 to H2O by the electron-transport chain beginning at the CoQ stage results in the synthesis of approximately 1.5 ATP per electron pair transferred
Electron-transfer flavoprotein (ETF)
long-chain enoyl co-As are converted to acetyl CoA and a shorter acyl CoA by mitochondrial … protein (more than one enzyme activity on a single polypeptide chain). This protein is also a … complex ( a complex of polypeptides catalyzing more than one rxn)
trifunctional; multienzyme
thiolase rxn of beta oxidation:
1. an active site … goup adds to the beta-keto group of acyl-CoA
2. C-C … yields a thioester between acyl CoA and the active site thiol group, together with an acetyl CoA carbanion intermediate stabilized by e- withdrawal into the thioester’s carbonyl group –> …
3. an enzyme acidic group protonates the .., yielding acetyl CoA
4&5.CoA displaces the enzyme … group from the enzyme-thioester intermediate, yielding an acyl CoA shorted by … C atoms
thiol;
bond cleavage; Claisen ester cleavage
acetyl-CoA carbanion
thiol; 2
Each round of β oxidation produces one …, one …, and one …. Oxidation of acetyl-CoA via the citric acid cycle generates an additional …and …., which are reoxidized through oxidative phosphorylation to form ATP.
NADH; FADH2; acetyl-CoA
FADH2; 3 NADH
the oxidation of one palmitate molecule has a net yield of …ATP.
106
A 𝛃,𝛄 Double Bond: The first enzymatic difficulty occurs after the third round of β oxidation: The resulting cis-β,γ double bond–containing enoyl-CoA is not a substrate for enoyl-CoA hydratase. …, however, converts the cis-Δ3 double bond to the …-Δ2 form. The Δ2 compound is the normal substrate of enoyl-CoA hydratase, so β oxidation can continue.
Enoyl-CoA isomerase; trans
A Δ4 Double Bond Inhibits…: The next difficulty arises in the fifth round of β oxidation: The presence of a double bond at an even-numbered carbon atom results in the formation of 2,4-dienoyl-CoA, which is a poor substrate for enoyl-CoA hydratase. However, NADPH-dependent 2,4- dienoyl-CoA reductase reduces the Δ4 double bond.
Enoyl-CoA Hydratase.
The Unanticipated Isomerization of 2,5-Enoyl-CoA by 3,2-Enoyl-CoA Isomerase: Mammalian 3,2-enoyl-CoA isomerase catalyzes a reversible reaction that interconverts Δ2 and Δ3 double bonds. A carbonyl group is stabilized by being conjugated to a…double bond. However, the presence of a Δ5 double bond (originating from an unsaturated fatty acid with a double bond at an odd-numbered C atom such as the Δ9 double bond of linoleic acid) is likewise stabilized by being conjugated with a Δ3 double bond. If a 2,5-enoyl-CoA is converted by 3,2-enoyl-CoA isomerase to …, which occurs up to 20% of the time, another enzyme is necessary to continue the oxidation:
Δ2; 3,5-enoyl CoA
The Unanticipated Isomerization of 2,5-Enoyl-CoA by 3,2-Enoyl-CoA Isomerase:
.. isomerizes the 3,5 diene to a 2,4 diene, which is then reduced by 2,4-dienoylCoA reductase and isomerized by 3,2-enoyl-CoA isomerase as in Problem 2 above. After two more rounds of β oxidation, the cis-Δ4 double bond originating from the cis-Δ12 double bond of linoleic acid is also dealt with as in Problem 2
3,5–2,4-Dienoyl-CoA isomerase
The final round of β oxidation of fatty acids with an odd # of Cs yields …, which is converted to … for entry into the citric acid cycle
propionyl-CoA; succinyl-CoA
(propionyl-CoA to succinyl-CoA) The first reaction, catalyzed by …, requires a biotin prosthetic group and is driven by the hydrolysis of ATP to ADP + Pi. The reaction resembles that of pyruvate carboxylase
propionyl-CoA carboxylase
(propionyl-CoA to succinyl-CoA) The (S)-methylmalonyl-CoA product of the carboxylase reaction is converted to the R form by …
methylmalonyl-CoA racemase
(propionyl-CoA to succinyl-CoA) (R)-Methylmalonyl-CoA is a substrate for …, which catalyzes an unusual carbon skeleton rearrangement
methylmalonyl-CoA mutase
the sixth ligand of 5’-deoxyadenosylcobalamin is a 5’-deoxyadenosyl group in which the deoxyribose C5’ atom forms a covalent … bond, one of only two carbon-metal bonds known in bio
C-Co
