T4. LIPID METABOLISM Flashcards
(141 cards)
1
Q
Where are lipids mainly found structurally?
A
cis structure
2
Q
What types of lipids exist?
A
saturated or unsaturated
3
Q
What percentage of body weight do lipids constitute?
A
5–25%
4
Q
What percentage of body lipids are TAGs?
A
0.9
5
Q
What portion of daily caloric intake comes from lipids?
A
36894
6
Q
Which organs rely on FA for 80% of their energy?
A
heart, muscle, and liver
7
Q
What are the structural functions of lipids?
A
biological membranes
8
Q
What signaling function do lipids perform?
A
information transporters
9
Q
What is the main reserve function of lipids?
A
long-term energy storage
10
Q
Why are lipids a better energy source than carbs or amino acids?
A
more reduced, provide double energy (9 kcal/g vs 4 kcal/g)
11
Q
Why are lipids better for storage than carbs?
A
found in anhydrous form
12
Q
What is the first step in lipid metabolism?
A
Bile salts emulsify dietary fats in the small intestine forming mixed micelles
13
Q
What is the second step in lipid metabolism?
A
Interstitial lipases degrade TAGs
14
Q
What is the third step in lipid metabolism?
A
FA and breakdown products are taken up by intestinal mucosa and converted into TAGs
15
Q
What is the fourth step in lipid metabolism?
A
TAGs are incorporated with cholesterol and apolipoproteins into chylomicrons
16
Q
What is the fifth step in lipid metabolism?
A
Chylomicrons move through lymphatic system and bloodstream
17
Q
What is the sixth step in lipid metabolism?
A
Lipoprotein lipase activated by apoC-II converts TAGs to FA and glycerol
18
Q
What is the seventh step in lipid metabolism?
A
FA enters the cell
19
Q
What are the three sources from which cells obtain fatty acids?
A
diet, fats stored in cells, fats synthesized and exported by other organs
20
Q
What are the three phases of FA catabolism?
A
mobilization of TAG reserves, transport to mitochondria, oxidation
21
Q
Where does mobilization of triacylglycerol reserves occur?
A
white adipose tissue
22
Q
Which hormones regulate FA degradation?
A
glucagon, catecholamines, thyropin, growth hormones, insulin
23
Q
What kind of reaction is TAG hydrolysis?
A
hydrolytic reaction catalyzed by three enzymes
24
Q
Why do adipocytes have few glucagon receptors?
A
favors slow degradation of TAGs to maintain survival with low amounts
25
What is the main hormone regulating FA degradation?
glucagon
26
What binds to the adipocyte membrane during fasting or stress?
glucagon or adrenaline
27
What is the first intracellular step after hormone binding in adipocytes?
activation of adenylyl cyclase via G proteins
28
What does adenylyl cyclase activation cause?
increased cAMP and PKA activation
29
What does PKA phosphorylate during lipolysis?
HSL (hormone-sensitive lipase)
30
What else does PKA phosphorylate during lipolysis?
perilipin molecules on lipid vacuole surface
31
What happens when perilipin is phosphorylated?
dissociates from CGI-58 protein
32
What happens after CGI-58 is released?
associates with ATGL and activates it
33
What does activated ATGL do?
hydrolyzes TAGs to DAGs + fatty acids
34
What does phosphorylated perilipin do next?
associates with phosphorylated HSL
35
What is the role of phosphorylated HSL?
degrades DAGs to MAGs and fatty acids
36
What enzyme acts on monoacylglycerols?
MGL
37
What does MGL produce?
glycerol and fatty acids
38
How are free fatty acids transported in the blood?
bound to albumin
39
How do fatty acids enter tissues like myocytes?
via specific transporter
40
What happens to fatty acids inside tissues?
oxidized to produce ATP
41
What happens to glycerol released during lipolysis?
goes to the liver
42
What is required for fatty acids with fewer than 12 carbons to enter the mitochondria?
They can enter mitochondria directly without activation.
43
What must happen to fatty acids longer than 14 carbons before mitochondrial entry?
They must be activated and transported.
44
Where does activation of long-chain fatty acids occur?
On the outer mitochondrial membrane.
45
What enzyme activates fatty acids?
Acetyl-CoA synthase.
46
How many isoforms does acetyl-CoA synthase have and what are they based on?
Three isoforms: short, medium, and long chain.
47
What molecule is used to transport long-chain fatty acids across the mitochondrial membrane?
Carnitine.
48
What enzyme facilitates the binding of Acyl-CoA to carnitine?
Carnitine acyltransferase.
49
What happens during the action of carnitine acyltransferase?
It binds Acyl-CoA to carnitine and releases CoA.
50
What is the purpose of the carnitine transport mechanism?
To recover the cytosolic carnitine pool.
51
Where is carnitine acyltransferase I located?
Outer mitochondrial membrane.
52
Where is carnitine acyltransferase II located?
Mitochondrial matrix.
53
What type of regulation do carnitine acyltransferases undergo?
Allosteric regulation.
54
What is the canonical pathway of beta-oxidation?
It involves the breakdown of even-chain saturated fatty acids.
55
How many carbon units are removed per beta-oxidation cycle?
Two carbon units are removed as one acetyl-CoA.
56
How many times is the beta-oxidation cycle repeated for palmitoyl-CoA?
Seven times.
57
What are the four steps of beta-oxidation?
Oxidation, hydration, second oxidation, thiolysis.
58
Which enzyme catalyzes the first oxidation in beta-oxidation?
Acyl-CoA dehydrogenase.
59
What does the first oxidation step in beta-oxidation generate?
FADH2.
60
Which enzyme performs the hydration step in beta-oxidation?
Enoyl-CoA hydratase.
61
Which enzyme catalyzes the second oxidation step in beta-oxidation?
β-hydroxyacyl-CoA dehydrogenase.
62
What does the second oxidation step in beta-oxidation generate?
NADH.
63
Which step in beta-oxidation is considered a limiting step?
The second oxidation by β-hydroxyacyl-CoA dehydrogenase.
64
What enzyme catalyzes thiolysis in beta-oxidation?
β-ketoacyl-CoA thiolase.
65
What does thiolysis use to cleave the molecule?
Coenzyme A (CoA).
66
What is generated in the first oxidation and where does it go?
FADH2, goes to respiratory chain via complex III after ETF reduction.
67
How much ATP is produced per FADH2 molecule?
1.5 ATP.
68
How much ATP is produced per NADH molecule?
2.5 ATP.
69
How many total ATPs are produced from palmitoyl-CoA?
108 ATPs.
70
How many ATPs are effectively net produced from palmitoyl-CoA?
107 ATPs, accounting for one ATP used in activation.
71
How many ATPs are generated from glucose degradation?
32 ATPs.
72
Why is beta-oxidation slower than glucose metabolism?
It requires oxygen and is a slower process.
73
Which additional enzymes are needed for monounsaturated fatty acid oxidation?
Enoyl-CoA isomerase.
74
What does enoyl-CoA isomerase do?
Transfers the double bond to be recognized by beta-oxidation enzymes.
75
Which additional enzyme is needed for polyunsaturated fatty acid oxidation?
2,4-dienoyl-CoA reductase.
76
Why is less ATP produced in unsaturated fatty acid oxidation?
The first oxidation step (FADH2 production) does not occur.
77
Do the additional enzyme reactions occur in every cycle of beta-oxidation for unsaturated FAs?
No, only in the cycle where the double bond appears.
78
What is produced in the last cycle of odd-chain fatty acid oxidation?
One Acetyl-CoA and one Propionyl-CoA.
79
What is the fate of Propionyl-CoA?
It is converted to succinyl-CoA, which can enter the CAC or be used in gluconeogenesis.
80
Where are branched fatty acids oxidized?
In peroxisomes.
81
What is the main difference in oxidation of branched fatty acids?
First oxidation is catalyzed by an oxidase, not dehydrogenase.
82
What does oxidase do in branched FA oxidation?
Transfers electrons from FADH2 to oxygen, producing H2O2.
83
Why is H2O2 production in peroxisomes dangerous?
H2O2 is highly damaging.
84
What neutralizes H2O2 in peroxisomes?
Peroxidase enzyme.
85
What must happen to NADH and Acetyl-CoA produced in peroxisomes?
They must be transported to mitochondria for further oxidation.
86
What happens when branched FA becomes short enough?
It is transferred to mitochondria.
87
What are alternative pathways to beta-oxidation?
Alpha and omega oxidation.
88
When are alpha and omega oxidation activated?
When beta-oxidation fails.
89
What limits the fatty acid degradation pathway?
Substrate availability.
90
What regulates substrate availability for FA degradation?
Mobilization of TAGs from adipose tissue.
91
What hormones regulate TAG hydrolysis in adipose tissue?
Glucagon, adrenaline, and insulin.
92
What enzyme is central to hormonal regulation of lipolysis?
Hormone-sensitive lipase (HSL).
93
How is HSL activity controlled?
By phosphorylation and dephosphorylation.
94
What effect does phosphorylation have on HSL?
Activates lipolysis.
95
What effect does dephosphorylation have on HSL?
Inhibits lipolysis.
96
What controls the phosphorylation state of HSL?
cAMP concentration.
97
What is the mechanism to transport fatty acids into mitochondria?
Carnitine shuttle system.
98
Where is CPT1 located?
On the outer mitochondrial membrane.
99
What enzyme facilitates the synthesis of acyl-carnitine?
Carnitine palmitoyltransferase I (CPT1).
100
What molecule allosterically inhibits CPT1?
Malonyl-CoA.
101
What is the effect of malonyl-CoA on fatty acid transport?
It inhibits CPT1 and prevents FA transport into mitochondria.
102
How many carbon atoms does malonyl-CoA have?
Three carbon atoms.
103
How is malonyl-CoA synthesized?
By carboxylation of acetyl-CoA in the cytosol.
104
Which enzyme synthesizes malonyl-CoA?
Acetyl-CoA carboxylase (ACAC).
105
What activates acetyl-CoA carboxylase (ACAC)?
Insulin.
106
How does insulin affect fatty acid transport?
It inhibits fatty acid transport into mitochondria by activating ACAC and increasing malonyl-CoA.
107
When does inhibition of fatty acid transport occur?
After eating (well-fed state), when fatty acid oxidation is not necessary.
108
Which enzyme is involved in the first oxidation step of β-oxidation?
β-dehydrogenase.
109
What inhibits β-dehydrogenase?
High [NADH]/[NAD+] ratio.
110
Which step of β-oxidation is inhibited by high Acetyl-CoA?
Thiolase activity.
111
What do high [NADH] and [Acetyl-CoA] levels indicate?
High energy load.
112
What are ketone bodies?
Soluble metabolites from fatty acid degradation that can cross the blood-brain barrier and be used as energy.
113
Where are ketone bodies synthesized?
In hepatic cell mitochondria.
114
Why does ketone body synthesis occur during fasting?
Gluconeogenesis depletes CAC intermediates, redirecting Acetyl-CoA to ketone synthesis.
115
What are the three ketone bodies?
Acetone, acetoacetate, and D-β-hydroxybutyrate.
116
Why doesn't acetone remain in the blood?
It is highly volatile.
117
What is required for ketone body synthesis?
Thiolase and acetyl-CoA.
118
Which cells can perform ketone body synthesis?
Only hepatic cells.
119
What enzyme is unique to liver cells for ketone body synthesis?
HMG-CoA synthase.
120
What reaction is catalyzed by HMG-CoA synthase?
Condensation of two acetyl-CoA molecules to form HMG-CoA.
121
What is the next step after HMG-CoA formation in ketone synthesis?
HMG-CoA lyase cleaves HMG-CoA to form acetoacetate and acetyl-CoA.
122
What are the two fates of acetoacetate?
Spontaneous decarboxylation to acetone or reduction to β-hydroxybutyrate.
123
Which enzyme reduces acetoacetate to β-hydroxybutyrate?
β-hydroxybutyrate dehydrogenase.
124
Where are ketone bodies released after synthesis?
Into the blood.
125
How is D-β-hydroxybutyrate degraded in other tissues?
Converted back to acetoacetate by β-hydroxybutyrate dehydrogenase.
126
What happens after acetoacetate is regenerated in peripheral tissues?
D-β-ketoacyl-CoA transferase transfers CoA from succinyl-CoA to acetoacetate.
127
What are the products of the CoA transfer step in ketone degradation?
Succinate and acetoacetyl-CoA.
128
What enzyme lyses acetoacetyl-CoA?
Thiolase.
129
What are the final products of ketone body degradation?
Two acetyl-CoA molecules.
130
Why can’t liver cells degrade ketone bodies?
They lack D-β-ketoacyl-CoA transferase.
131
Why can only liver cells synthesize ketone bodies?
They exclusively express HMG-CoA synthase.
132
What causes disorders related to trans fats?
High intake of trans fats from animal and industrial sources.
133
What is the industrial source of trans fats?
Hydrogenation of vegetable polyunsaturated fats.
134
How much does high trans fat consumption increase the risk of death?
By 34%, mainly from heart disease.
135
Why do trans fats alter cholesterol synthesis?
Partial degradation in β-oxidation allows escape from mitochondria, interfering with cholesterol metabolism.
136
What are some effects of altered cholesterol metabolism?
Membrane degradation, altered gene expression.
137
What is ketoacidosis?
Accumulation of ketone bodies in the blood.
138
What is ketonuria?
Presence of ketone bodies in the urine.
139
What conditions cause ketonuria?
Diabetes, malnutrition, vomiting, high protein diets, or lack of glucose.
140
What is the effect of sustained increase in ketosis?
Increased acetoacetate and β-hydroxybutyrate in blood, decreased pH (acidosis).
141
What can extreme acidosis from ketosis lead to?
Coma and death.
