Lecture 25 - Lipid Metabolism Flashcards
1
Q
for mammals, what is 5-25% of body weight due to?
A
fat and lipids
2
Q
for mammals, what is 90% of their weight?
A
triaclglycerols
3
Q
how is fat stored in humans?
A
- adipocytes
- primarily subcutaneous + abdominal cavity
4
Q
are fats soluble?
A
highly insoluble
5
Q
how is fat digested?
A
by enzumes
6
Q
where is fat transported?
A
through plasma
7
Q
what is the process of fat absorption?
A
cellular uptake
8
Q
what is a result of fat being so insoluble?
A
-digestion, transport + absorption are problematic
9
Q
what is the digestion of fat facilitated by?
A
bile salt in the intestines
10
Q
what do bile salts do?
A
-emulsifying fat to aid in their hydrolysis
11
Q
what does pancreatic lipase do?
A
breaks down fat
12
Q
what does pancreatic lipase generate?
A
-mixture of glycerol, fatty acids, mono + di-acylglycerols
13
Q
fats are aggregated by certain ______ into ________ called _______
A
proteins
water-soluble units
lipoproteins
14
Q
where are lipoproteins transported?
A
through plasma
15
Q
how are lipoproteins divided?
A
by size, composition, and morphology
16
Q
what are lipoproteins divided into?
A
-chylomicrons and lipoproteins of various densities
17
Q
what are dietary triacylglycerols carried by?
A
lipoproteins
18
Q
what are dietary triaclyglycerols targed by?
A
cell surface receptors
19
Q
what happens after dietary triaclyglycerols have been targeted by cell surface receptors?
A
- they are hydrolyzed by lipoprotein lipase
- transported into cytosol
20
Q
how are triacylglycerols in adipose cells mobilized?
A
- by their hydrolysis in the cytosol
- using a hormone-sensitive lipase
21
Q
where are the fatty acids released?
A
- into the blood
- carried by 66-kD protein albumin
22
Q
fatty acids are ____ before they are degraded
A
activated
23
Q
what is required to activate fatty acids?
A
- ATP and CoA
- catalyzed by acyl-CoA synthetase
24
Q
What is the result of the hydrolysis of PPi for the activation of fatty acids?
A
pushes quilibriium far to the right
25
what is the reaction of fatty acid activation?
Fatty acid + CoA + ATP <> Acyl-CoA + AMP + PPi
26
why are there different acyl-CoA synthetases?
-specific to fatty acids of different length acyl chains
27
where does fatty acid activation happen?
-in the cytosol
28
where does the rest of the oxidation of fatty acid occur?
mitochondria
29
where does the degredation of fatty acids take place?
mitochondria
30
what happens to the acyl group during fatty acid degradation?
-acyl group is transferred to a carnitine
31
what happens to the carnitine during fatty acid degradation?
transported into the mitochrondrial matrix by a carnitine transporter
(unloads cargo on inside then carnitine shuttled back out)
32
what finally happens during fatty acid degradation?
-fatty acid then oxidized completely into acetyl-CoA
33
what kind of pathway is fatty acid degradation?
spiral pathway
| beta oxidation of fatty acids
34
what is a spiral pathway?
- each round the acyl chain is shortended by 2Cs
| - splitting out acetyl-CoA
35
what kind of reaction does the spiral fatty acid degradation pathway involve?
- oxidation reaction
| - occurs 2 C away from C=o group (beta)
36
what can be done with each acetyl-CoA?
each acetyl-CoA can be fed into the citric acid cycle
37
what does beta oxidation itself generate?
1 NADH
| 1 QH2
38
what does the degradation of unsaturated acyl chains require?
isomerization and reduction
39
what are the 4 (different) steps of degredation of unsaturated fatty acids?
1. after 3 rounds, oxidation of linoleate must be isomerized into trans form
2. next round proceeds as usual
3. reductase (which requires NADPH) used to remove one double bond when another cis double bond is encountered
4. isomerase to relocate double bond
40
what is a major difference in the beta oxidation of odd-numbered-chain fatty acids?
-acyl chains with odd number of carbons produces propionyl-CoA instead of acetyl-CoA
41
how is the beta oxidation of odd-numbered-chain fatty acids remedied?
- extend it using a carboxylase
| - turn it into a citric cycle intermediate
42
where does some fatty acid oxidation occur?
in peroxisomes
43
what is a peroxisome?
single-membrane bound
44
in plants where does all fatty acid oxidation take place?
in peroxisomes and glyoxysomes
45
where does most mammalian fatty acid oxidation occur?
mitochodnria
46
what happens to electrons in peroxisomal beta oxidation?
-electrons removed are deposited into O2 to make peroxide H2O2
47
what is the peroxisome responsible for?
shortening very long acyl chains
48
what else is carried out in peroxisomes?
branched-chain beta oxidation
49
where does synthesis of fatty acids occur?
solely i the cytosol on the smooth ER
50
in the synthesis of fatty acids, starting from acetyl-CoA ____ are added at at a time
2 Cs
51
the ______ pathway for fatty acids is very different from the beta oxidation and uses different ________
anabolic
| enzymes
52
what is the key coenzye in fatty acid synthesis?
acyl-carrier (AC) arm, phosphorylated to a Ser on the enzyme fatty acid synthase
53
how does fatty acid synthesis start?
with the carboxylation of Acetyl-CoA
54
what is the first step of fatty acid synthesis?
-elongating the C2 in acetyl-CoA by carboxylase
55
what are the first 3 steps of fatty acid synthesis?
1. 1 ATP required to load CO2 onto biotin
2. malonyl group transferred to ACP
3. Malonyl-ACP adds two carbons at a time to the chain using a mechanism similar to pyruvate carboxylase
56
what catalyzes all 7 steps of fatty acid synthesis?
fatty acid synthase
57
every step in fatty acid synthesis is carried out on a __________
single multi-function enzyme
58
where are the 2NADPH needed for fatty acid synthesis supplied by?
pentose phosphate pathway
59
during fatty acid synthesis what happens each time malonate is loaded onto ACP?
1 ATP is required (to carboxylate biotin)
60
how do you synthesize a C16 palmitate?
7 rounds of the fatty acid synthesis reaction must e repeated
61
what is the total energy cost of fatty acid synthesis?
7 ATP + 14 NADPH
62
fatty acid synthase can only synthesize saturated acyl chains up to _____
C16
63
some sphingolipids contain ____ and ____ fatty acids
C22 and C24
64
what is arachidonic acid?
- precursor to the eicosanoids
- C20 fatty acid
- multiple unsaturated C=C bonds
65
how are double bonds added to C16 palmitate?
by desaturase enzymes via a dehydrogenation rxn (an oxidation) where electrons are transferred to O2 making H2O
66
what can elongation be catalyzed by?
elongase
67
what is the result of mammals not being able to introduce a C=C bond beyond C9?
fatty acids like linoleate must be acquired in their diet for these so-called "essential fatty acids"
68
does the brain metabolize fat for energy?
no
69
why does the brain not metabolize fat for energy?
-lipids do not cross the blood/brain barrier
70
how does the brain get its energy?
relies on glucose
71
what are ketone bodies?
- class of molecules synthesized from acetyl-CoA
| - supplemental source of energy in ketogenesis
72
what are ketone bodies?
- water soluble
| - can pass through into central nervous system
73
how are triacylglycerols and phospholipids synthezied?
-from acyl-CoA groups using a citric cycle intermediate
74
how are fatty acid acyl groups activated in triacylycerosl?
activated by acyl-CoA syntheses
fatty acid + CoA + ATP ,. acyl-CoA + AMP + PPi
75
how does cholesterol synthesis begin?
- with acetyl-CoA
| - in a reaction that is similar to the first step in ketogenesis
76
where does cholesterol synthesis occur?
in the cytosol
77
what does mevalonate acquire in cholesterol synthesis?
- 2 PO4
| - is decarboxylated to produce a C5 molecule
78
what is isopentenyl pyrophosphate?
-precursor to cholesterol + other isoprenoids
79
what is the final step of cholesterol synthesis?
- 6 isopentenyl pyrophosphates are condensed together
| - forming a C30 compound squalene
80
what is cholesterol synthesis inhibited by?
-statins
81
what do statins bind to?
-they bind irreversibly to HMG-CoA reductase
82
what are another effect of statins?
- also shut off the synthesis of other isoprenoids
| - long-term use carries adverse affects
83
what are the 4 ways that cholesterol are used?
1. membrane additive
2. precursor to bile acids (cholate)
3. precursor to steroid hormones (testosterone + estrogen)
4. acylated to form a cholesteryl ester for storage or for packaging in VLDL
84
where can cells acquire cholesterol from?
cells can synthesize/acquire cholesterol from circulating LDL
85
what are HDL essential for?
essential for removing excess cholesterol from cells
