Chapter 20 Flashcards
1
Q
… are hydrophobic lipids consisting of glycerol triesters of fatty acids such as palmitic and oleic acids
A
triacylglycerols
2
Q
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 …
A
lipid-water interfaces; surface area; bile acids
3
Q
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
A
bile acids; bile salts
4
Q
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 …
A
1,2-diacylglycerols; 2-acylglycerols; soaps; interfacial activation.
5
Q
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.
A
colipase
6
Q
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 …
A
intestinal mucosa; absorption of the digestion products
7
Q
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 …
A
intestinal wall
8
Q
Bile acids are likewise required for the efficient intestinal absorption of the …
A
lipid-soluble vitamins A, D, E, and K.
9
Q
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
A
intestinal fatty acid–binding protein (I-FABP)
10
Q
….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.
A
Lipoproteins
11
Q
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
A
chylomicrons
12
Q
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.
A
very low density lipoproteins; intermediate density lipoproteins; low density lipoproteins; High density lipoproteins
13
Q
the HDL, which are the most …of the lipoproteins, are also the
A
dense; smallest
14
Q
The protein components of lipoproteins are known as …or just …
A
apolipoproteins; apoproteins
15
Q
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.
A
hydrophilic; hydrophobic; amphipathic
16
Q
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
A
lipoprotein lipase
17
Q
The chylomicrons shrink as their triacylglycerols are p rogressively hydrolyzed until they are reduced to cholesterol
enriched …
A
chylomicron remnants
18
Q
Chylomicrons therefore deliver dietary triacylglycerols to …and …tissue, and dietary …to the liver
A
muscle; adipose; cholesterol
19
Q
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 …
A
energy; resynthesize triacylglycerols; dihydroxyacetone phosphate
20
Q
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.
A
IDL; LDL
21
Q
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
A
taking up LDL; receptor-mediated endocytosis
22
Q
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 …
A
clathrin-coated pits; clathrin-coated vesicles
23
Q
, 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
A
endosomes
24
Q
… is a general mechanism whereby cells take up large molecules, each through a corresponding specifi c receptor
A
Receptor-mediated endocytosis
25
HDL have essentially the opposite function of LDL: They ...from the tissues
remove cholesterol
26
A circulating HDL particle acquires its cholesterol by extracting it from ...
cell-surface membranes.
27
The ...is the only organ capable of disposing of significant quantities of cholesterol
liver
28
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
29
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
30
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
31
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
32
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
33
...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
34
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).
2. Hydration of the double bond by ... (EH) to form a ...
acyl-CoA dehydrogenase; enoyl-CoA hydratase; 3-L-hydroxyacyl-CoA.
35
The degradation of fatty acyl-CoA via β oxidation occurs in four reactions:
3. NAD+-dependent dehydrogenation of the β-hydroxyacyl-CoA by ...(HAD) to form the corresponding β-ketoacyl-CoA.
4. 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
36
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
37
...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)
38
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
39
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
40
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
41
the oxidation of one palmitate molecule has a net yield of ...ATP.
106
42
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
43
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.
44
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
45
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
46
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
47
(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
48
(propionyl-CoA to succinyl-CoA) The (S)-methylmalonyl-CoA product of the carboxylase reaction is converted to the R form by ...
methylmalonyl-CoA racemase
49
(propionyl-CoA to succinyl-CoA) (R)-Methylmalonyl-CoA is a substrate for ..., which catalyzes an unusual carbon skeleton rearrangement
methylmalonyl-CoA mutase
50
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
51
The active sites of nearly all α/β barrel enzymes are located at the ...ends of the barrel’s β strands. In methylmalonyl-CoA mutase, however, the AdoCbl is packed against the ....ends of the barrel’s β strands
C-terminal ; N-terminal
52
In free AdoCbl, the Co atom is axially liganded by an N atom of its DMB group and by the adenosyl residue’s 5′-CH2 group. In the enzyme, however, the DMB has swung aside to bind in a separate pocket and has been replaced by the side chain of...from the C-terminal domain. The adenosyl group is not visible in the structure due to disorder and hence has probably also swung aside.
His 610
53
In nearly all other α/β barrel–containing enzymes, the center of the barrel is occluded by large, often branched, ...side chains. In methylmalonyl-CoA mutase, however, the 2-carboxypropyl-CoA’s pantetheine group binds in a narrow tunnel along the center of the α/β barrel to put the methylmalonyl group of an intact substrate in close proximity to the unliganded face of the cobalamin ring. the tunnel is lined by small .. residues
hydrophobic; hydrophilic
54
The proposed methylmalonyl-CoA mutase reaction mechanism begins with the ... of the cobalamin C—Co bond; in other words, the C and Co atoms each acquire one of the electrons that formed the cleaved electron pair bond. The Co ion therefore alternates between its Co(III) and Co(II) oxidation states and hence functions as a reversible ...
homolytic cleavage; free radical generator.
55
M ethylmalonyl- CoA mutase catalyzes the conversion of a metabolite to a citric acid cycle intermediate other than.... However, such C4 intermediates are actually .., not substrates, of the citric acid cycle. In order for succinyl-CoA to undergo net oxidation by the citric acid cycle, it must first be converted to and then to...
acetyl-CoA; catalysts; pyruvate; acetyl-CoA
56
In mammalian cells, the bulk of β oxidation occurs in the mitochondria, but
....also oxidize fatty acids, particularly those with very long chains or branched chains.
peroxisomes
57
Peroxisomal
β oxidation, which differs only slightly from mitochondrial β oxidation, shortens very long chain fatty acids (>... carbon atoms), which are then fully degraded by the mitochondrial pathway.
22
58
(peroxisomal beta oxidation) ...catalyzes the reaction Fatty acyl-CoA + O2 →trans-Δ2-enoyl-CoA + H2O2 The enzyme uses an FAD cofactor, but the abstracted electrons are transferred directly to O2 to yield ...(hydrogen peroxide; hence the name “peroxisome”) rather than passing through the electron-transport chain with its concomitant oxidative phosphorylation
Acyl-CoA oxidase; H2O2
59
(peroxisomal beta oxidation) Peroxisomal fatty acid oxidation therefore generates ...fewer ATP per C2 cycle than mitochondrial fatty acid oxidation. ...converts the H2O2 produced in the oxidase reaction to H2O + O2.
1.5; Catalase
60
(peroxisomal beta oxidation) Peroxisomal enoyl-CoA hydratase and 3-L-hydroxyacyl-CoA dehydrogenase activities occur on a .... The reactions catalyzed are identical to those of the mitochondrial system
single polypeptide
61
(peroxisomal beta oxidation)... catalyzes the final step of oxidation. This enzyme is almost inactive with acyl-CoAs of length ...or less, so peroxisomes incompletely oxidize fatty acids
Peroxisomal thiolase; C8
62
By a process known as ..., acetyl-CoA is converted to acetoacetate or D-𝛃-hydroxybutyrate. These compounds together with acetone are somewhat inaccurately referred to as ...
ketogenesis; ketone bodies
63
(acetoacetate formation) Two molecules of acetyl-CoA are condensed to ... by thiolase (also called acetyl-CoA acetyltransferase) working in the reverse direction from the way it does in the final step of β oxidation
acetoacetyl-CoA
64
(acetoacetate formation) Condensation of the acetoacetyl-CoA with a third acetyl-CoA by ....orms 𝛃-hydroxy-𝛃-methylglutaryl-CoA (HMG-CoA). The mechanism of this reaction resembles the reverse of the thiolase reaction in that an active site thiol group forms an acyl-thioester intermediate
HMGCoA synthase
65
(acetoacetate formation) HMG-CoA is degraded to ...and …. in a mixed a ldol–Claisen ester cleavage by HMG-CoA lyase. The mechanism of this reaction is analogous to the reverse of the citrate synthase reaction.
acetoacetate; acetyl-CoA
66
(acetoacetate formation) HMG-CoA is also a precursor in ...biosynthesis. HMG-CoA lyase is present only in liver mitochondria and therefore does not interfere with cholesterol synthesis in the cytoplasm.
cholesterol
67
Acetoacetate may be reduced to D-β-hydroxybutyrate by ...
𝛃-hydroxybutyrate dehydrogenase
68
Fatty acid biosynthesis occurs through ..., the reverse of the β -oxidation process.
condensation of C2 units
69
Acetyl-CoA enters the cytosol in the form of ...via the ... ATP-citrate lyase then catalyzes the reaction
Citrate + CoA + ATP → acetyl-CoA + oxaloacetate + ADP + Pi
citrate; tricarboxylate transport system
70
...(ACC) catalyzes the first committed step of fatty acid biosynthesis and one of its rate-controlling steps. The reaction occurs in two steps, a CO2 activation and a carboxylation. The result is a three-carbon (malonyl) group linked as a ...to CoA
Acetyl-CoA carboxylase; thioester
71
There are two major isoforms of ACC. ... occurs in adipose tissue and ...occurs in tissues that oxidize but do not synthesize fatty acids, such as heart muscle
ACC1; ACC2
72
The product of the ACC-catalyzed reaction, ..., strongly inhibits the mitochondrial import of fatty acylCoA for fatty acid oxidation, the major control point for this process. Thus it appears that ACC2 has a regulatory function
malonyl-CoA
73
Although fatty acid synthesis begins with the synthesis of a CoA ester, malonyl-CoA, the growing fatty acid is anchored to ... (ACP
acyl-carrier protein
74
(rxns catalyzed by mammalian fatty acid synthase) These are priming reactions in which the synthase is “loaded” with the precursors for the condensation reaction. In mammals, ... (MAT) catalyzes two similar reactions at a single active site: An acetyl group originally linked as a thioester in acetyl-CoA is transferred to ACP (1a), and a malonyl group is transferred from malonyl-CoA to ACP (1b).
malonyl/ acetylCoA-ACP transacylase
75
(rxns catalyzed by mammalian fatty acid synthase) The 𝛃-ketoacyl-ACP synthase (KS; also known as condensing enzyme) first transfers the acetyl group from ACP to an enzyme ...(2a). In the condensation reaction (2b), the malonyl-ACP is decarboxylated, and the resulting carbanion attacks the acetylthioester to form a four- carbon ...
Cys residue; acetoacetyl-ACP
76
(rxns catalyzed by mammalian fatty acid synthase) Two reductions and a dehydration convert the β-keto group to an ...group. The coenzyme in both reductive steps is .... In β oxidation, the analogs of Reactions 3 and 5, respectively, use NAD+ and FAD. Moreover, Reaction 4 requires a D-β-hydroxyacyl substrate, whereas the analogous reaction in β oxidation forms the corresponding L isomer.
alkyl; NADPH
77
the fatty acid grows from its ...end, not from its methyl end
thioester
78
Palmitate, a saturated C16 fatty acid, is converted to longer chain saturated and unsaturated fatty acids through the actions of ...and ...
elongases; desaturases
79
Unsaturated fatty acids are produced by ...
terminal desaturases
80
... must consequently be obtained in the diet (ultimately from plants that have Δ12- and Δ15- desaturases) and is therefore an ...
Linoleic acid; essential fatty acid.
81
Triacylglycerols are synthesized from ... and ... or….
fatty acyl-CoA esters; glycerol-3- phosphate; dihydroxyacetone phosphate
82
The dihydroxyacetone phosphate used to make glycerol-3-phosphate for triacylglycerol synthesis comes either from glucose via the .. (Fig. 15-1) or from ...via an abbreviated version of gluconeogenesis (Fig. 16-15) termed ....
glycolytic pathway; oxaloacetate; glyceroneogenesis
83
Synthesis and breakdown of glycogen and triacylglycerols are processes that concern the whole organism, with its organs and tissues forming an interdependent network connected by the ...
bloodstream
84
As in glycogen metabolism (Section 16-3), hormones such as insulin and glucagon regulate the rates of the opposing pathways of lipid metabolism and thereby control whether fatty acids will be ...or ....
oxidized; synthesized
85
Fatty acid oxidation is regulated largely by the concentration of fatty acids in the blood, which is, in turn, controlled by the hydrolysis rate of triacylglycerols in adipose tissue by ...
hormone-sensitive triacylglycerol lipase.
86
cAMP-dependent phosphorylation simultaneously stimulates ...and inhibits...
fatty acid oxidation; fatty acid synthesis.
87
The ... therefore determines the rate and direction of fatty acid metabolism.
glucagon:insulin ratio
88
Factors such as substrate availability, allosteric interactions, and covalent modification (phosphorylation) control enzyme activity with response times of minutes or less. Such ... is complemented by ..., which requires hours or days and governs a pathway’s regulatory enzyme by altering the amount of enzyme present. This is accomplished through changes in the rates of protein ...
short-term regulation; long-term regulation; synthesis and/or breakdown.
89
an abundance of glucose, reflected in the level of insulin, promotes ... and the storage of fatty acids by adipocytes, whereas starvation, when glucose is unavailable, ...fatty acid synthesis and the uptake of fatty acids by adipocytes.
fatty acid synthesis;decreases
90
Glycerophospholipids have significant asymmetry in their C1- and C2-linked fatty acyl groups: C1 substituents are mostly ...fatty acids, whereas those at C2 are, by and large, ...fatty acids
saturated; unsaturated
91
In mammals, the head groups ethanolamine and choline are activated before being attached to the lipid:
1. ATP phosphorylates the ... group of choline or ethanolamine.
2. The phosphoryl group of the resulting phosphoethanolamine or ...then attacks CTP, displacing PPi, to form the corresponding CDP derivatives, which are ... of the polar head group.
OH
phosphocholine
activated phosphate esters
92
In mammals, the head groups ethanolamine and choline are activated before being attached to the lipid:
3. The C3-OH group of 1,2-diacylglycerol attacks the phosphoryl group of the activated CDP–ethanolamine or CDP–choline, displacing CMP to yield the corresponding …..
glycerophospholipid
93
William Lands showed that such side chain specificity results from “remodeling” reactions in which specific acyl groups of individual glycerophospholipids are exchanged by specific ...and ...
phospholipases; acyltransferases
94
Eukaryotic membranes contain signifi cant amounts of two other types of glycerophospholipids: ..., which contain a hydrocarbon chain linked to glycerol C1 via a vinyl ether linkage, and ... in which the alkyl substituent at glycerol C1 is attached via an ether linkage
plasmalogens; alkylacylglycerophospholipids,
95
Most sphingolipids are ...; that is, their polar head groups consist of carbohydrate units. ...are ceramide monosaccharides, whereas ...are sialic acid–containing ceramide oligosaccharides
sphingoglycolipids; cerebrosides; gangliosides
96
N-Acylsphingosine is synthesized in four reactions from the precursors palmitoyl-CoA and serine:
1. ... catalyzes condensation of palmitoyl-CoA with serine, yielding 3-ketosphinganine.
2. ... catalyzes the NADPHdependent reduction of 3-ketosphinganine’s keto group to form sphinganine (dihydrosphingosine).
3-Ketosphinganine synthase; 3-Ketosphinganine reductase
97
N-Acylsphingosine is synthesized in four reactions from the precursors palmitoyl-CoA and serine:
3. ...is formed by transfer of an acyl group from an acyl-CoA to sphinganine’s 2-amino group, forming an amide bond.
4. ...converts dihydroceramide to ceramide by an FAD-dependent oxidation reaction.
Dihydroceramide; Dihydroceramide dehydrogenase
98
Defects in the pathways for degrading these complex lipids are responsible for certain ...
lipid storage diseases
99
...and related compounds (Fig. 9-12) are derivatives of C20 fatty acids such as arachidonate, which is released from membrane phospholipids in response to hormones and other signal
Prostaglandins
100
In a healthy organism, an intricate balance is maintained between the biosynthesis, utilization, and transport of ..., keeping its harmful deposition to a minimum
cholesterol
101
... condense to form a linear molecule with 30 carbons that cyclizes to form the four-ring structure of cholesterol
isoprene units
102
...Is a Key Cholesterol Precursor
HMG-CoA
103
(cholesterol biosynthesis) 1. The CoA thioester group of HMG-CoA is reduced to an alcohol in an NADPH-dependent four-electron reduction catalyzed by HMG-CoA reductase, yielding ..., a C6 compound. This is the rate- determining step of cholesterol biosynthesis.
mevalonate
104
(cholesterol biosynthesis)
2. The new OH group is phosphorylated by ....
3. The phosphate group is converted to a pyrophosphate by …
4. The molecule undergoes an ATP-dependent decarboxylation reaction catalyzed by pyrophosphomevalonate decarboxylase to yield ...
mevalonate-5-phosphotransferase; phosphomevalonate kinase; isopentenyl pyrophosphate
105
(cholesterol biosynthesis-part 2) ...catalyzes the head-to-tail condensation of dimethylallyl pyrophosphate and isopentenyl pyrophosphate to yield the C10 compound geranyl pyrophosphate.
Prenyltransferase
106
(cholesterol biosynthesis-part 2) Prenyltransferase catalyzes a second head-to-tail condensation of geranyl pyrophosphate and isopentenyl pyrophosphate to yield the C15 compound .... The prenyltransferase catalyzes an SN1 reaction to form a carbocation intermediate with an ionization–condensation– elimination mechanism
farnesyl pyrophosphate
107
(cholesterol biosynthesis-part 2) 3... then catalyzes the head-to-head condensation of two farnesyl pyrophosphate molecules to form squalene.
. Squalene synthase
108
(cholesterol biosynthesis-part 2) ..., a linear hydrocarbon, cyclizes to form the tetracyclic steroid skeleton. this is converted to 2,3-oxidosqualene which then cyclizises to … which rearranges to … which is converted to cholesterol over a 19 step process
Squalene; protosterol; lanosterol
109
The bile acids that escape this recycling are further metabolized by intestinal microorganisms and excreted. This is the only route for...
cholesterol excretion.
110
...which catalyzes the rate-limiting step of cholesterol biosynthesis, is the pathway’s main regulatory site
HMG-CoA reductase,
111
The primary regulatory mechanism for HMG-CoA reductase activity is long-term feedback control of the ...
amount of enzyme present in the cell
112
High levels of circulating cholesterol, a condition known as hypercholesterolemia, can be treated with drugs called ...that inhibit HMG-CoA reductase
statins
113
This high degree of ...between the statins and the active site, a result of the enzyme’s ... accounts for the extremely low inhibition constants.
complementarity ; flexibility
114
...is a slow progressive disease that begins with the deposition of lipids in the walls of large blood vessels, particularly the coronary arteries
Atherosclerosis
115
The development of atherosclerosis is strongly correlated with the concentration of circulating ..
LDL
116
Individuals with the inherited disease familial hypercholesterolemia (FH) are deficient in functional ...
LDL receptors
117
The long-term ingestion of a high-fat/high-cholesterol diet has an effect similar to although not as extreme as ..
. familial hypercholesterolemia
118
Triacylglycerol digestion depends on the emulsifying activity of... and the activation of ...at the lipid–water interface.
bile acids; lipases
119
..., complexes of nonpolar lipids surrounded by a coat of amphipathic lipids and apolipoproteins, transport lipids in the bloodstream. Cells take up cholesterol and other lipids by the receptor-mediated endocytosis of LDL.
Lipoproteins
120
Fatty acid oxidation begins with the activation of the acyl group by formation of a ...with CoA. The acyl group is transferred to carnitine for transport into the mitochondria, where it is re-esterified to ...
thioester; CoA
121
β oxidation occurs in four reactions: (1) formation of an ..., (2) ...of the double bond, (3) ....to form a β-ketoacylCoA, and (4) ...by CoA to produce acetyl-CoA and an acyl-CoA shortened by two carbons. This process is repeated until fatty acids with even numbers of carbon atoms are converted to a...and the fatty acids with odd numbers of carbon atoms are converted to ...and one molecule of .... The acetyl-CoA is oxidized by the citric acid cycle and oxidative phosphorylation to generate ATP. Propionyl-CoA is converted to the citric acid cycle intermediate ..., in part, by the coenzyme B12-containing enzyme methylmalonyl-CoA mutase.
```
α,β double bond
hydration
dehydrogenation
thiolysis
acetyl-CoA
acetyl-CoA; propionyl-CoA
succinyl-CoA
```
122
The oxidation of unsaturated fatty acids requires an ...to convert Δ3 double bonds to Δ2 double bonds and a ...to remove Δ4 double bonds. The oxidation of odd-chain fatty acids yields propionyl-CoA, which is converted to succinyl-CoA through a cobalamin (B12)-dependent pathway. Very long chain fatty acids are partially oxidized by a three-enzyme system in ....
isomerase; reductase; peroxisomes
123
The liver uses acetyl-CoA to synthesize the ketone bodies ...and...., which are released into the bloodstream. Tissues that use the ketone bodies for fuel convert them back to acetyl-CoA.
acetoacetate ; β-hydroxybutyrate
124
In fatty acid synthesis, mitochondrial acetyl-CoA is shuttled to the cytosol via the ... and activated to malonylCoA by the action of acetyl-CoA carboxylase.
tricarboxylate transport system
125
A series of seven enzymatic activities, which in mammals are contained in a multifunctional homodimeric enzyme, extend acyl-ACP chains by ...carbons at a time. An enzyme-bound acyl group and malonyl-ACP condense to form a ... and .... Two reductions and a dehydration yield an acyl-ACP in a series of reactions that resemble the reverse of β oxidation but are catalyzed by separate enzymes in the cytosol. ...(C16), the normal product of fatty acid biosynthesis, is synthesized in seven such reaction cycles and is then cleaved from ACP by a thioesterase.
two; β-ketoacyl intermediate; CO2; Palmitate
126
Other fatty acids are synthesized from palmitate through the action of elongases and desaturases. Human triacylglycerols synthesized from fatty acyl-CoA and glycerol-3-phosphate or dihydroxyacetone phosphate tend to contain saturated fatty acids at ... and unsaturated fatty acids at ....
C1; C2
127
The opposing pathways of fatty acid degradation and synthesis are hormonally regulated. ...and … activate hormone-sensitive lipase in adipose tissue, thereby increasing the supply of fatty acids for oxidation in other tissues, and inactivate acetyl-CoA carboxylase. ...has the opposite effect. it also regulates the levels of acetyl-CoA carboxylase and fatty acid synthase by controlling their ...
Glucagon; epinephrine; Insulin; Insulin
