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

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2
Q

A major source of carbon for fatty acid synthesis is

A

dietary carbohydrates

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3
Q

Fatty acid synthesis occurs primarily in the ____. But also in the ____,_____, _____

A

liver. But also in the brain, kidneys, and adipose tissue

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4
Q

Fatty acids synthesis takes place in the ______ in contrast to degradation that takes place primarily in the

A

Cytoplasm, mitochondrial matrix

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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)
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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)
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7
Q

The formation of _____ is the committed step in fatty acid synthesis

A

Malonyl CoA

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8
Q

The synthesis of Malonyl CoA from Acetyl CoA is catalyzed by

A

Acetyl CoA carboxylase 1 , which contains a biotin prosthetic group

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9
Q

Intermediates in fatty acid synthesis are attached to an ______ carrier protein

A

acyl carrier protein (ACP)

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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

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11
Q

The enzymes of fatty acid synthesis are jointed in a single polypeptide chain called ______.

A

fatty acid synthase

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12
Q

Pyruvate dehydrogenase catalyzes

A

Pyruvate+ SH-CoA + NAD+ ——> Acetyl CoA + NADH + CO2

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13
Q

Pyruvate Carboxylase catalyzes

A

pyruvate to OAA

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14
Q

Citrate lyase catalyzes

A

Citrate +ATP ——> OAA + Acetyl CoA + ADP + Pi

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15
Q

Cytosolic malate dehydrogenase catalyzes

A

OAA + NADH —–> Malate + NAD+

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16
Q

Malic enzyme catalyzes

A

Malate + NADP+ ——–> NADPH + CO2 + pyruvate

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17
Q

Acetyl CoA carboxylase (ACC) catalyzes

A

Acetyl CoA + CO2 + ATP + Biotin (prosthetic group) —–> Malonyl CoA + ADP + Pi

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18
Q

Acetyl CoA is converted to malonyl CoA by ______

A

carboxylation using enzyme Acetyl CoA carboxylase (ACC)

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19
Q

The function of Acetyl CoA carboxylase (ACC) is to add ____ to acetyl CoA

A

CO2

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20
Q

Malonyl CoA contains ___ carbons while Acetyl CoA contains ___ carbons

A

3, 2

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21
Q

Acetyl CoA carboxylase (ACC) is allosterically regulated by

A
  • Citrate (+)

- Long chain fatty acids (-)

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22
Q

Acetyl CoA carboxylase (ACC) is positively allosterically regulated by

A

Citrate

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23
Q

Acetyl CoA carboxylase (ACC) is negatively allosterically regulated by

A

long chain fatty acids

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24
Q

Phosphorylation has what effect on Acetyl CoA carboxylase (ACC)

A

negative/ inhibits

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25
Q

Dephosphorylation has what effect on Acetyl CoA carboxylase (ACC)

A

positive/ induces it

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26
Q

Insulin has what effect on Acetyl CoA carboxylase (ACC)

A

Induce

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27
Q

Glucagon and epinephrine have what effect on Acetyl CoA Carboxylase (ACC)

A

inhibit it

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28
Q

Gene expression of Acetyl CoA Carboxylase is up-regulated by

A

high carbohydrate/low fat diet

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29
Q

Gene expression of Acetyl CoA carboxylase is down-regulated by

A

high fat/ low carbohydrate diet

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30
Q

The reactions of fatty acid synthesis occur on the

A

fatty acid synthase complex

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31
Q

____ carbon units form malonyl CoA are sequentially added to the growing fatty acyl chain to form _____ (16:0)

A

two, Palmitate

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32
Q

Fatty acid synthase (FAS) is a large _______ complex

A

multi-enzyme

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33
Q

Fatty acid synthase is a _____ is composed of ___ identical sub-units. (____kDa each)

A

dimer, composed of 2 identical subunits , 260 KDa each

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34
Q

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

A

7, Acyl carrier protein (ACP)

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35
Q

The acyl carrier protein (ACP) on fatty acid synthase has a ________ residue

A

phosphopantetheine (PP)

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36
Q

Two monomers of FAS arrange in a ______ conformation- with phosphopantetheine (PP) of one aligned with a _____ group of another

A

Head to tail, cysteinyl sulfhydryl group

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37
Q

ACP has a _____ arm

A

flexible arm ( Phosphopantetheine (PP))

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38
Q

The elongation phase of fatty acid synthesis starts with

A

the formation of acetyl ACP and Malonyl ACP

using Acetyl transacylase and malonyl transacyclase respectively

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39
Q

beta-ketoacyl synthase catalyzes

A

The condensation reaction in fatty acid synthesis

  • Acetyl ACP + Malonyl ACP —-> acetoacetyl ACP + ACP + CO2
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40
Q

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

A

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

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41
Q

Beta-Ketoacylsynthase catalyzes

A

The first reduction in fatty acid synthesis

Acetoacetyl ACP + NADPH + H+ ——> D-3-Hydroxybutryryl ACP + NADP+

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42
Q

3-Hydroxyacyl dehydratase catalyzes

A

Dehydration reaction in fatty acid synthesis

D-3-Hydroxybutyryl ACP —-> Crotonyl ACP + H2O

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43
Q

Enoyl Reductase catalyzes

A

The second reduction in fatty acid synthesis

Crotonyl ACP + NADPH + H+ —–> butyryl ACP + NADP+

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44
Q

Stoichiometry: Palmitate synthesis reaction

A

8 Acetyl CoA + 7 ATP + 14 NADPH + (6H+) = CH3(CH2)14COO- (palmitate) + (14 NADP +) + 8 CoA + 6H2O + 7 ADP + 7Pi

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45
Q

Fatty Acid Synthase allosteric is increased by what kind of diet

A

High carbohydrate / low fat

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46
Q

Fatty Acid synthase is inhibited by what type of diet

A

high fat diet as well as starvation

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47
Q

The major product of fatty acid synthase is _____

A

palmitate

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48
Q

longer fatty acids are formed by elongation reactions catalyzed by enzymes on the cytoplasmic face of the ______-

A

Endoplasmic Reticulum (ER)

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49
Q

What has an allosteric effect on regulation of FAS

A

presence of phosphorylated sugars

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50
Q

Endoplasmic reticulum enzymes responsible for the generation of unsaturated fatty acids

A
  • NADH-cytochrome b5 reductase
  • cytochrome b5
  • Stearoyl CoA desaturase
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51
Q

NADH-Cytochrom b5 reductase catalyzes

A
  • The first step in the generation of unsaturated fatty acids
  • transferes electrons form NADH to FAD.
52
Q

Explain the sequence of events on the endoplasmic reticulum that leads to the production of unsaturated fatty acids

A

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
Q

Glycerol phosphate dehydrogenase catalyzes

A

DHAP + NADH ——> Glycerol 3-P + NAD+

54
Q

Glycerol kinase catalyzes

A

Glycerol + ATP —–> ADP + Glycerol 3-P

55
Q

Glycerol 3-P + 2 Acyl-CoA —–>

A

Phosphatidic acid + 2 CoA

56
Q

Diacylglycerol + Acyl-CoA —->

A

Triacylglycerol (TAG) + CoA

57
Q

TAG packaged with apoproteins to form ________ and secreted into blood

A

Very low density lipoproteins (VLDL)

58
Q

_______ converts Acetyl CoA carboxylase into an inactive form by modifying three ____ residues

A

AMP- Activated protein kinase(AMPK), serine

59
Q

Eicosanoids are products generated by the oxidation of _____ carbon fatty acids (_______)

A

20 carbon fatty acids (Arachidonic acid)

60
Q

Eicosandoid hormones are derived form

A

polyunsaturated fatty acids

61
Q

Eicosandoids are ____ lived molecules, that serve as local ___-

A

short, hormones

62
Q

What are the 4 families of Eicosanoids

A
  • Prostaglandins
  • Prostacyclin
  • Thromboxane
  • leukotrienes
63
Q

Eicosanoids are ____ molecules and serve as _____ molecules

A

signaling molecules and serve as messenger molecules

64
Q

eicosanoids influence many pathways involved in _____, ______, ______, and ______

A

growth, inflammation, infection, and immunity

65
Q

Prostaglandin synthase catalyzes

A

Arachidonate —–> Prostaglandin H2 (PGH2)

66
Q

Lipoxygenases catalyze

A

Arachidonate —–> Leukotrienes

67
Q

DG lipase catalyzes

A

Diacylglycerols —-> Arachidonate

68
Q

PLA2 catalyzes

A

Phospholipids —–> Arachidonate

69
Q

Thromboxane synthase catalyzes

A

Prostaglandin H2 (PGH2) —-> Thromboxanes

70
Q

Prostacyclin synthase catalyzes

A

Prostaglandin H2 (PGH2) —–> prostacyclin

71
Q

ASA inhibits what enzyme

A

Prostaglandin synthase

72
Q

Metabolic action (s) of PGD2

A

Promotion of sleep

73
Q

Metabolic action (s) of PGE2

A

smooth muscle contraction
inducing pain, heat, and fever
bronchoconstriction

74
Q

Metabolic action (s) of PGF2alpha

A

Uterine contraction

75
Q

Metabolic action (s) of TXA2

A
  • Stimulation of platelet aggregation

- Vasoconstriction

76
Q

Metabolic action(s) of PGI2

A
  • Inhibition of platelet aggregation
  • Vasodilation
  • embryo implantation
77
Q

Metabolic action (s) of LTB4

A

Leukocyte chemotaxis

78
Q

Phosphatidic acid ——> Pi + Diacylglycerol is catalyzed by

A

Phosphatase

79
Q

There are how many mechanisms to form phospholipids

A

2 different mechanisms

80
Q

In mechanism 1 of phospholipid synthesis phosphatidic acid is cleaved by phosphatase to form _______

A

Diacylglycerol (DAG)

81
Q

In mechanism 1 of phospholipid synthesis diacylglycerol (DAG) reacts with various ______ to form different phospholipids

A

headgroups

82
Q

In mechanism 1 of phospholipid synthesis the headgroups must be _____ prior to this reaction

A

activated (this is done with headgroup reacting with CTP) thus making a CDP-headgroup

83
Q

In mechanism 1 of phospholipid synthesis the activated headgroup (CDP-headgroup) reacts with diaylglycerol (DAG) to form

A

glycerophospholipid and CMP

84
Q

What are the two major phospholipids produced by mechanism 1 of phospholipid synthesis

A
  • Phosphatidylcholine (PC)

- Phosphatidylethanolamine (PE)

85
Q

What are the two major phospholipids produced by mechanism 2 of phospholipid synthesis

A
  • Cardiolipin

- Phosphatidylinositol (PI)

86
Q

In mechanism 2 of phospholipid synthesis phosphatidic acid reacts with ____ to form ______ and ___

A

CTP to form CDP-Diacylglycerol (DAG) and PPi

87
Q

In mechanism 2 of phospholipid synthesis CDP-DAG reacts with ____ to form phosphatidylinositol (PI) and CMP

A

inositol

88
Q

In mechanism 2 of phospholipid synthesis CDP-DAG reacts with _______ to form diphosphatidyl glycerol (Cardiolipin), a component of the inner mitochondrial membrane

A

Phosphatidyl glycerol

89
Q

In mechanism 2 of phospholipid synthesis CDP-DAG reacts with phosphatidyl glycerol to form ________, a component of the inner mitochondrial membrane

A

diphosphatidyl glycerol (cardiolipin)

90
Q

Phosphatidylserine (PS) is formed by exchanging _____ for serine

A

ethanolamine of Phosphotidylethanolamine (PE)

91
Q

Phosphatidylserine (PS) can be reconverted to Phosphotidylethanolamine (PE) by _____

A

decarboxylation

92
Q

Phosphotidylethanolamine (PE) can me ______ to form Phosphatidylcholine (PC)

A

Methylated

93
Q

What is the most abundant sterol

A

cholesterol (about 0.05% of total body weight)

94
Q

Cholesterol is a component of membranes and precursor of biological active compounds such as

A
  • bile acids and bile salts
  • Vitamin D
  • Steroid hormones (progesterone, aldosterone, cortisol, testosterone, estradiol)
95
Q

What is the daily intake of cholesterol and about what percent is absorbed in the gut

A

about 250 mg per day, about 30-60% is absorbed in the gut

96
Q

What is the daily production of cholesterol and where is it produced

A

about 1 gram, mostly in the liver

97
Q

Biosynthesis of cholesterol is regulated by

A

dietary intake

98
Q

What is the daily excretion percentage of cholesterol

A

about 5%

99
Q

What is the daily re-absorption percentage of cholesterol

A

about 95%

100
Q

Cholesterol is a ______ compound made of ____ (#) fused rings

A

allicyclic compound, 4 fused rings

101
Q

What is the molecular weight of cholesterol

A

386 kDa

102
Q

Cholesterol has ____ carbons, ___ rings, ___ double bonds between _______, ___ 2 CH3 at C__ and C___, ___ member hydrocarbon chain attached to _____

A

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
Q

3-hyroxy-3 methylglutaryl CoA reductase (HMG CoA Reductase) catalyzes

A

First step in the synthesis of cholesterol (rate limiting step)

Acetyl CoA + NADPH —-> Mevalonate + NADP+

104
Q

What is the target for statins

A

HMG CoA reductase

105
Q

what is a major carrier of cholesterol in the blood

A

Low density lipoprotein

106
Q

Cholesterol is synthesized form ____ in how many stages

A

Acetyl CoA in 3 stages

107
Q

What are the 3 stages of cholesterol synthesis

A
  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
Q

The synthesis of _____ is the committed step in cholesterol formation

A

mevalonate

109
Q

The the cytoplasm HMG-CoA is converted into ______. In the mitochondria it is converted into ____ and ____

A

Mevalonate, Acetyl CoA and Acetoacetate

110
Q

Mevalonate is converted into 3-isopentenyl pyrophosphate in 3 consecutive reactions each requiring _____. In the last step, the release of ____ yields isopentenyl pyrophosphate

A

ATP, CO2

111
Q

The conversion of mevalonate to 3-isopentenyl is induced by

A

ATP

112
Q

The conversion of mevalonate to 3-isopentenyl is inhibited by

A

CO2

113
Q

Squalene (C30) is synthesized from ___ molecules of isopentenyl pyrophosphate (C5)

A

6

114
Q

Stage II of the biosynthesis of cholesterol starts with the

A

isomerization of isopentenyl pyrophosphate to dimethylallyl pyrophosphate

115
Q

The last step in the in the synthesis of squalene is a

A

reductive tail-to-tail condensation of two molecules of frankly pyrophosphate catalyzed by the ER enzyme squalene synthase

116
Q

Stage III of cholesterol biosynthesis

A

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
Q

Oxidosqualene cyclase holds

A

squalene epoxide in an appropriate conformation and initiates the reaction by pronating the epoxide oxygen

118
Q

The role of LDL is to

A

transport cholesterol to peripheral tissues and regulate de novo cholesterol synthesis at these sites

119
Q

LDL is composed of

A
  • unesterified cholesterol
  • phospholipid
  • cholesteryl ester
  • apolipoprotein B-100
120
Q

what are the three bad cholesterol particles

A

VLDL
IDL
LDL

121
Q

what is good cholesterol particle

A

HDL

122
Q

HDL properties

A
  • smallest
  • most dense
  • high protein and phospholipid content
123
Q

HDL has what three Apoproteins

A

ApoA-I
ApoC-II
Apo-E

124
Q

VLDL has what three Apoproteins

A

ApoB-100
ApoC-II
Apo-E

125
Q

IDL has what two apoproteins

A

ApoB-100

ApoE

126
Q

LDL has what one apoproteins

A

ApoB-100