Lipid metabolism II Flashcards
1
Q
How can one have excess triacylglycerol stores if the fat intake in diet is low
A
Major source of carbon for fatty acid synthesis is dietary carbohydrates
2
Q
A major source of carbon for fatty acid synthesis is
A
dietary carbohydrates
3
Q
Fatty acid synthesis occurs primarily in the ____. But also in the ____,_____, _____
A
liver. But also in the brain, kidneys, and adipose tissue
4
Q
Fatty acids synthesis takes place in the ______ in contrast to degradation that takes place primarily in the
A
Cytoplasm, mitochondrial matrix
5
Q
Components of fatty acid synthesis are located in the cytoplasm. what are they
A
- enzymes
- Acyl carrier proteins
- Co-factors
- Reducing power
- Energy (ATP)
6
Q
What ar the major steps in the synthesis of fatty acids
A
- formation of acetyl CoA
- Conversion of Acetyl CoA to malignly CoA
- Elongation (addition of carbons)
- Desaturation (introduction of double bonds)
7
Q
The formation of _____ is the committed step in fatty acid synthesis
A
Malonyl CoA
8
Q
The synthesis of Malonyl CoA from Acetyl CoA is catalyzed by
A
Acetyl CoA carboxylase 1 , which contains a biotin prosthetic group
9
Q
Intermediates in fatty acid synthesis are attached to an ______ carrier protein
A
acyl carrier protein (ACP)
10
Q
intermediates in fatty acid synthesis are attached to the _______ of an _______, whereas intermediates in fatty acid breakdown are covalently attached to the _______ group of ______
A
Sulfhydryl group of an acyl carrier protein (ACP), Sulfhydryl group of Coenzyme A
11
Q
The enzymes of fatty acid synthesis are jointed in a single polypeptide chain called ______.
A
fatty acid synthase
12
Q
Pyruvate dehydrogenase catalyzes
A
Pyruvate+ SH-CoA + NAD+ ——> Acetyl CoA + NADH + CO2
13
Q
Pyruvate Carboxylase catalyzes
A
pyruvate to OAA
14
Q
Citrate lyase catalyzes
A
Citrate +ATP ——> OAA + Acetyl CoA + ADP + Pi
15
Q
Cytosolic malate dehydrogenase catalyzes
A
OAA + NADH —–> Malate + NAD+
16
Q
Malic enzyme catalyzes
A
Malate + NADP+ ——–> NADPH + CO2 + pyruvate
17
Q
Acetyl CoA carboxylase (ACC) catalyzes
A
Acetyl CoA + CO2 + ATP + Biotin (prosthetic group) —–> Malonyl CoA + ADP + Pi
18
Q
Acetyl CoA is converted to malonyl CoA by ______
A
carboxylation using enzyme Acetyl CoA carboxylase (ACC)
19
Q
The function of Acetyl CoA carboxylase (ACC) is to add ____ to acetyl CoA
A
CO2
20
Q
Malonyl CoA contains ___ carbons while Acetyl CoA contains ___ carbons
A
3, 2
21
Q
Acetyl CoA carboxylase (ACC) is allosterically regulated by
A
- Citrate (+)
- Long chain fatty acids (-)
22
Q
Acetyl CoA carboxylase (ACC) is positively allosterically regulated by
A
Citrate
23
Q
Acetyl CoA carboxylase (ACC) is negatively allosterically regulated by
A
long chain fatty acids
24
Q
Phosphorylation has what effect on Acetyl CoA carboxylase (ACC)
A
negative/ inhibits
25
Dephosphorylation has what effect on Acetyl CoA carboxylase (ACC)
positive/ induces it
26
Insulin has what effect on Acetyl CoA carboxylase (ACC)
Induce
27
Glucagon and epinephrine have what effect on Acetyl CoA Carboxylase (ACC)
inhibit it
28
Gene expression of Acetyl CoA Carboxylase is up-regulated by
high carbohydrate/low fat diet
29
Gene expression of Acetyl CoA carboxylase is down-regulated by
high fat/ low carbohydrate diet
30
The reactions of fatty acid synthesis occur on the
fatty acid synthase complex
31
____ carbon units form malonyl CoA are sequentially added to the growing fatty acyl chain to form _____ (16:0)
two, Palmitate
32
Fatty acid synthase (FAS) is a large _______ complex
multi-enzyme
33
Fatty acid synthase is a _____ is composed of ___ identical sub-units. (____kDa each)
dimer, composed of 2 identical subunits , 260 KDa each
34
Each monomer of fatty acid synthase has _____ catalytic sites, which is the amount required for activity, as well as an _______. despite this monomers are not active and a dimer is required
7, Acyl carrier protein (ACP)
35
The acyl carrier protein (ACP) on fatty acid synthase has a ________ residue
phosphopantetheine (PP)
36
Two monomers of FAS arrange in a ______ conformation- with phosphopantetheine (PP) of one aligned with a _____ group of another
Head to tail, cysteinyl sulfhydryl group
37
ACP has a _____ arm
flexible arm ( Phosphopantetheine (PP))
38
The elongation phase of fatty acid synthesis starts with
the formation of acetyl ACP and Malonyl ACP
| using Acetyl transacylase and malonyl transacyclase respectively
39
beta-ketoacyl synthase catalyzes
The condensation reaction in fatty acid synthesis
- Acetyl ACP + Malonyl ACP ----> acetoacetyl ACP + ACP + CO2
40
Why does the initial condensation reaction in fatty acid make s 4-Carbon unit form 3C and 2C molecules and not 2 Acetyl ACP (2-C) molecules
The equilibrium for the synthesis of acetoacetyle ACP form two molecules of acetyl ACP is highly unfavorable . In contrast the equilibrium is favorable if Malonyl ACP is reactant because its decarboxylation contributes a substantial decrease in free energy
41
Beta-Ketoacylsynthase catalyzes
The first reduction in fatty acid synthesis
Acetoacetyl ACP + NADPH + H+ ------> D-3-Hydroxybutryryl ACP + NADP+
42
3-Hydroxyacyl dehydratase catalyzes
Dehydration reaction in fatty acid synthesis
D-3-Hydroxybutyryl ACP ----> Crotonyl ACP + H2O
43
Enoyl Reductase catalyzes
The second reduction in fatty acid synthesis
Crotonyl ACP + NADPH + H+ -----> butyryl ACP + NADP+
44
Stoichiometry: Palmitate synthesis reaction
8 Acetyl CoA + 7 ATP + 14 NADPH + (6H+) = CH3(CH2)14COO- (palmitate) + (14 NADP +) + 8 CoA + 6H2O + 7 ADP + 7Pi
45
Fatty Acid Synthase allosteric is increased by what kind of diet
High carbohydrate / low fat
46
Fatty Acid synthase is inhibited by what type of diet
high fat diet as well as starvation
47
The major product of fatty acid synthase is _____
palmitate
48
longer fatty acids are formed by elongation reactions catalyzed by enzymes on the cytoplasmic face of the ______-
Endoplasmic Reticulum (ER)
49
What has an allosteric effect on regulation of FAS
presence of phosphorylated sugars
50
Endoplasmic reticulum enzymes responsible for the generation of unsaturated fatty acids
- NADH-cytochrome b5 reductase
- cytochrome b5
- Stearoyl CoA desaturase
51
NADH-Cytochrom b5 reductase catalyzes
- The first step in the generation of unsaturated fatty acids
- transferes electrons form NADH to FAD.
52
Explain the sequence of events on the endoplasmic reticulum that leads to the production of unsaturated fatty acids
First, electrons are transferred from NADH to the FAD moiety of NADH-Cytochrom b5 reductase. The heme iron atom of cytochrome b5 is then reduced to the Fe2+ state. The noontime iron atom of the Stearoyl CoA denatures is subsequently converted into the Fe2+ state, which enables it to interact with O2 and the saturated fatty acyl CoA substrate (stearoyl CoA) . A double bond is formed in the fatty acid substrate (making it Oleoyl CoA) and two molecules of H2O are released. Two electrons come from NADH and two from the single bond the fatty acyl substrate
53
Glycerol phosphate dehydrogenase catalyzes
DHAP + NADH ------> Glycerol 3-P + NAD+
54
Glycerol kinase catalyzes
Glycerol + ATP -----> ADP + Glycerol 3-P
55
Glycerol 3-P + 2 Acyl-CoA ----->
Phosphatidic acid + 2 CoA
56
Diacylglycerol + Acyl-CoA ---->
Triacylglycerol (TAG) + CoA
57
TAG packaged with apoproteins to form ________ and secreted into blood
Very low density lipoproteins (VLDL)
58
_______ converts Acetyl CoA carboxylase into an inactive form by modifying three ____ residues
AMP- Activated protein kinase(AMPK), serine
59
Eicosanoids are products generated by the oxidation of _____ carbon fatty acids (_______)
20 carbon fatty acids (Arachidonic acid)
60
Eicosandoid hormones are derived form
polyunsaturated fatty acids
61
Eicosandoids are ____ lived molecules, that serve as local ___-
short, hormones
62
What are the 4 families of Eicosanoids
- Prostaglandins
- Prostacyclin
- Thromboxane
- leukotrienes
63
Eicosanoids are ____ molecules and serve as _____ molecules
signaling molecules and serve as messenger molecules
64
eicosanoids influence many pathways involved in _____, ______, ______, and ______
growth, inflammation, infection, and immunity
65
Prostaglandin synthase catalyzes
Arachidonate -----> Prostaglandin H2 (PGH2)
66
Lipoxygenases catalyze
Arachidonate -----> Leukotrienes
67
DG lipase catalyzes
Diacylglycerols ----> Arachidonate
68
PLA2 catalyzes
Phospholipids -----> Arachidonate
69
Thromboxane synthase catalyzes
Prostaglandin H2 (PGH2) ----> Thromboxanes
70
Prostacyclin synthase catalyzes
Prostaglandin H2 (PGH2) -----> prostacyclin
71
ASA inhibits what enzyme
Prostaglandin synthase
72
Metabolic action (s) of PGD2
Promotion of sleep
73
Metabolic action (s) of PGE2
smooth muscle contraction
inducing pain, heat, and fever
bronchoconstriction
74
Metabolic action (s) of PGF2alpha
Uterine contraction
75
Metabolic action (s) of TXA2
- Stimulation of platelet aggregation
| - Vasoconstriction
76
Metabolic action(s) of PGI2
- Inhibition of platelet aggregation
- Vasodilation
- embryo implantation
77
Metabolic action (s) of LTB4
Leukocyte chemotaxis
78
Phosphatidic acid ------> Pi + Diacylglycerol is catalyzed by
Phosphatase
79
There are how many mechanisms to form phospholipids
2 different mechanisms
80
In mechanism 1 of phospholipid synthesis phosphatidic acid is cleaved by phosphatase to form _______
Diacylglycerol (DAG)
81
In mechanism 1 of phospholipid synthesis diacylglycerol (DAG) reacts with various ______ to form different phospholipids
headgroups
82
In mechanism 1 of phospholipid synthesis the headgroups must be _____ prior to this reaction
activated (this is done with headgroup reacting with CTP) thus making a CDP-headgroup
83
In mechanism 1 of phospholipid synthesis the activated headgroup (CDP-headgroup) reacts with diaylglycerol (DAG) to form
glycerophospholipid and CMP
84
What are the two major phospholipids produced by mechanism 1 of phospholipid synthesis
- Phosphatidylcholine (PC)
| - Phosphatidylethanolamine (PE)
85
What are the two major phospholipids produced by mechanism 2 of phospholipid synthesis
- Cardiolipin
| - Phosphatidylinositol (PI)
86
In mechanism 2 of phospholipid synthesis phosphatidic acid reacts with ____ to form ______ and ___
CTP to form CDP-Diacylglycerol (DAG) and PPi
87
In mechanism 2 of phospholipid synthesis CDP-DAG reacts with ____ to form phosphatidylinositol (PI) and CMP
inositol
88
In mechanism 2 of phospholipid synthesis CDP-DAG reacts with _______ to form diphosphatidyl glycerol (Cardiolipin), a component of the inner mitochondrial membrane
Phosphatidyl glycerol
89
In mechanism 2 of phospholipid synthesis CDP-DAG reacts with phosphatidyl glycerol to form ________, a component of the inner mitochondrial membrane
diphosphatidyl glycerol (cardiolipin)
90
Phosphatidylserine (PS) is formed by exchanging _____ for serine
ethanolamine of Phosphotidylethanolamine (PE)
91
Phosphatidylserine (PS) can be reconverted to Phosphotidylethanolamine (PE) by _____
decarboxylation
92
Phosphotidylethanolamine (PE) can me ______ to form Phosphatidylcholine (PC)
Methylated
93
What is the most abundant sterol
cholesterol (about 0.05% of total body weight)
94
Cholesterol is a component of membranes and precursor of biological active compounds such as
- bile acids and bile salts
- Vitamin D
- Steroid hormones (progesterone, aldosterone, cortisol, testosterone, estradiol)
95
What is the daily intake of cholesterol and about what percent is absorbed in the gut
about 250 mg per day, about 30-60% is absorbed in the gut
96
What is the daily production of cholesterol and where is it produced
about 1 gram, mostly in the liver
97
Biosynthesis of cholesterol is regulated by
dietary intake
98
What is the daily excretion percentage of cholesterol
about 5%
99
What is the daily re-absorption percentage of cholesterol
about 95%
100
Cholesterol is a ______ compound made of ____ (#) fused rings
allicyclic compound, 4 fused rings
101
What is the molecular weight of cholesterol
386 kDa
102
Cholesterol has ____ carbons, ___ rings, ___ double bonds between _______, ___ 2 CH3 at C__ and C___, ___ member hydrocarbon chain attached to _____
Cholesterol has 27 carbons, 4 rings, 1 double bond between C5 and C6, 2 CH3 at C18 and C19, 1 OH at C3, 8 member hydrocarbon chain attached to C17
103
3-hyroxy-3 methylglutaryl CoA reductase (HMG CoA Reductase) catalyzes
First step in the synthesis of cholesterol (rate limiting step)
Acetyl CoA + NADPH ----> Mevalonate + NADP+
104
What is the target for statins
HMG CoA reductase
105
what is a major carrier of cholesterol in the blood
Low density lipoprotein
106
Cholesterol is synthesized form ____ in how many stages
Acetyl CoA in 3 stages
107
What are the 3 stages of cholesterol synthesis
1. ) synthesis of isopentenyl pyrophosphate, an activated isoprene unit that is the key building block of cholesterol
2. ) Stage two is the condensation of six molecules of isopentenyl pyrophosphate to form squalene
3. ) in stage three, squalene cyclizes and the tetracyclic product is subsequently converted into cholesterol
Note that the first stage takes place in the cytoplasm and the next tow in the endoplasmic reticulum
108
The synthesis of _____ is the committed step in cholesterol formation
mevalonate
109
The the cytoplasm HMG-CoA is converted into ______. In the mitochondria it is converted into ____ and ____
Mevalonate, Acetyl CoA and Acetoacetate
110
Mevalonate is converted into 3-isopentenyl pyrophosphate in 3 consecutive reactions each requiring _____. In the last step, the release of ____ yields isopentenyl pyrophosphate
ATP, CO2
111
The conversion of mevalonate to 3-isopentenyl is induced by
ATP
112
The conversion of mevalonate to 3-isopentenyl is inhibited by
CO2
113
Squalene (C30) is synthesized from ___ molecules of isopentenyl pyrophosphate (C5)
6
114
Stage II of the biosynthesis of cholesterol starts with the
isomerization of isopentenyl pyrophosphate to dimethylallyl pyrophosphate
115
The last step in the in the synthesis of squalene is a
reductive tail-to-tail condensation of two molecules of frankly pyrophosphate catalyzed by the ER enzyme squalene synthase
116
Stage III of cholesterol biosynthesis
Starts with cyclization of squalene. Squalene is first activated by conversion into squalene epoxide (2,3-oxidosqualene) in a reaction that uses O2 and NADPH. Squalene epoxide is then cyclized to lanosterol by oxidosqualene cyclase.
117
Oxidosqualene cyclase holds
squalene epoxide in an appropriate conformation and initiates the reaction by pronating the epoxide oxygen
118
The role of LDL is to
transport cholesterol to peripheral tissues and regulate de novo cholesterol synthesis at these sites
119
LDL is composed of
- unesterified cholesterol
- phospholipid
- cholesteryl ester
- apolipoprotein B-100
120
what are the three bad cholesterol particles
VLDL
IDL
LDL
121
what is good cholesterol particle
HDL
122
HDL properties
- smallest
- most dense
- high protein and phospholipid content
123
HDL has what three Apoproteins
ApoA-I
ApoC-II
Apo-E
124
VLDL has what three Apoproteins
ApoB-100
ApoC-II
Apo-E
125
IDL has what two apoproteins
ApoB-100
| ApoE
126
LDL has what one apoproteins
ApoB-100
