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MCBM EXAM 3-Preview > WK1_5 Alternative Fatty Acid Oxidation / Fatty Acid Synthesis and Metabolism > Flashcards

WK1_5 Alternative Fatty Acid Oxidation / Fatty Acid Synthesis and Metabolism Flashcards

1
Q

fatty acid (FA) metabolism couples to central metabolic pathways through..

A

Acetyl-CoA

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2
Q

free fatty acids (FA) can be taken up by most tissue and used as energy source except.. (2)

A

brain and RBCs

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3
Q

greater 90% of FA in plasma are esters (_____, _____, and ______)

A

TAGs, cholesterol esters, phospholipids

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4
Q

does saturated FA have double bonds?

A

no

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5
Q

does unsaturated FA have double bonds?

A

yes

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6
Q

between the 2 double bonds present in unsaturated FA, which one is natural?

A

cis

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7
Q

trans double bonds are produced as by-product of _____

A

hydrogenation

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8
Q

which double bond is solid at body temperature?

A

trans

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9
Q

in FA nomenclature, carboxylate is numbered as carbon #_

A

1

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10
Q

in FA nomenclature, number before colon represents..

A

length of chain

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11
Q

in FA nomenclature, number after colon represents..

A

how many double bonds

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12
Q

in FA nomenclature, numbers in parentheses represents..

A

positions in unsaturation

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13
Q

carbon at methyl terminus is the ______ carbon

A

omega

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14
Q

FA biosynthesis occurs primarily in the..

A

liver cytosol

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15
Q

T/F mitochondrial Acetyl-CoA cannot be exported to the cytosol

A

TRUE

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16
Q

acetyl moiety enters ctyosol as _____ following condensation with oxaloacetate

A

citrate

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17
Q

acetyl moiety enters cytosol as citrate following..

A

condensation with oxaloacetate

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18
Q

regulation of transport is via [?], which is high under the fed state

A

[citrate]

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19
Q

regulation of transport is via [citrate], which is high under the _____ state

A

fed state

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20
Q

during fed state, large amounts of ATP inhibit _____ in TCA cycle

A

isocitrate dehydrogenase

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21
Q

oxaloacetate is transported back into _____ through transporters, permuting efficient cycle of transfer of acetate into cytosol

A

mitochondrila matrix

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22
Q

regulation of fatty acid biosynthesis is through..

A

Acetyl-CoA carboxylase

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23
Q

biotin mediates carboxylation of acetyl ova through a ______ type of mechanism

A

swinging arm

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24
Q

insulin activates through…

A

phosphatase activation

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25
Q

insulin activates through phosphatase activation (______)

A

fed state

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26
Q

insulin-dependent activation of Acetyl-CoA carboxylase ______ fatty acid biosynthesis

A

upregulates

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27
Q

FA synthesis occurs in the ______ and uses ______

A

cytosol; NADPH (not NADH)

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28
Q

FA is cleaved by..

A

palmitoyl thiesterase

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29
Q

further ______ and ______ of FA occurs in smooth ER

A

elongation; desaturation

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30
Q

carbon skeleton rearrangements set enzyme up for next..

A

condensation

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31
Q

2 carbon acetate condenses with Malonyl-CoA, with release of..

A

carbon dioxide

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32
Q

______ enhances availability of extracellular fatty acids to permit adipose tissue uptake and formation of TAGs

A

insulin

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33
Q

LPL _____ FA on TAGs in chylomicrons

A

hydrolyzes

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34
Q

______ transport FA

A

adipocytes

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35
Q

______ is basic building bock for TAG synthesis

A

glycerol

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36
Q

in _____, glycerol kinase phosphorylates glycerol released following delivery of FA to adipose tissue

A

liver

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37
Q

synthesis of TAG involves activation of FA by _____ and _____

A

CoA-SH; sequential condensation

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38
Q

_____ mobilizes fats (TAGs) in adipose tissue

A

epinephrine

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39
Q

_____ blocks lipolysis through activation of phosphodiesterase (hydrolysis of cAMP) to enhance synthesis of fats

A

insulin

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40
Q

mobilization of FA reserves in adipocytes is initiated by _____

A

hormone sensitive lipase

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41
Q

hormonal activation of cAMP-dependent protein kinase through _____

A

adenylate cyclase

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42
Q

phosphorylation of lipase initiates TAG _____

A

degradation

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43
Q

phosphorylation of acetyl CoA carboxylase _____ FA synthesis

A

inhibits

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44
Q

glycerol is released and transported to liver for _____

A

reuptake

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45
Q

FA transported to tissues in complex with..

A

albumin

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46
Q

beta oxidation of fatty acids occurs in ______

A

mitochondrial matrix

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47
Q

FA is activated by conjugation with..

A

HS-CoA

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48
Q

what kind of molecule is carnitine?

A

carrier molecule

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49
Q

FA acyl chain is transferred to carnitine by..

A

carnitine palmitoyl transferase

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50
Q

malonyl CoA _____ carnitine palmitoyl transferase preventing FA synthesis from occurring simultaneously as oxidation

A

inhibits

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51
Q

net production of _____ ATP per palmitate oxidized

A

129

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52
Q

formation of ketone bodies arise from elevations in..

A

lacetyl-CoA

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53
Q

where does ketone body formation occur?

A

in liver

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54
Q

formation of CoA allows..

A

FA oxidation

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55
Q

ethanol metabolism involves formation of _____, and can deplete _____ needed for glycolysis

A

NADH; NAD+

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56
Q

excess NADH causes metabolic disorders, including inhibition of _____ and _____

A

TCA cycle; FA oxidation

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57
Q

accumulation of FA in liver can result in fatty liver (_____)

A

steatosis

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58
Q

metabolism of ethanol results in large increases in..

A

NADH

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59
Q

_____ is _inhibited due to depletion of oxaloacetate

A

TCA cycle

60
Q

_____ is inhibited due to depletion of pyruvate

A

gluconeogenesis

61
Q

_____ is inhibited due to depletion of NAD+

A

glycolysis

62
Q 
which of the following lipid designations corresponds to stearic acid (sterate)?
A) 16:0
B) 16:1
C) 18:0
D) 18:1
E) 20:4
A

C: stearic acid has 18 carbons and fully reduced

63
Q

what molecule acts as the carbon carrier to move acetyl CoA across the mitochondrial membrane for fatty acid biosynthesis?

A

citrate

64
Q

which cofactor/vitamin is used to transfer carboxylate moieties?

A

biotin

65
Q

which apolipoprotein acts to transport lipids from the liver to peripheral tissues?

A

VLDL

66
Q

alcoholism typically requires consumption of 30-50% of total calories as ethanol, and is commonly associated with increases in which metabolite?

A

ketone bodies + NADH

67
Q

what are the functions of cholesterol?

A
  • structural component in membranes

- precursor of bile acids/steroid hormones/vitamin D

68
Q

what are the regulations of cholesterol?

A
  • liver plays central role in regulating cholesterol availability
  • cholesterol precipitates along endothelial lining of blood vesicles (plaque formation ) contributing to cardiovascular disease
69
Q

_____ catalyzes rate limiting step of cholesterol biosynthesis

A

HMG CoA reductase

70
Q

_____ provides all carbons for cholesterol biosynthesis

A

acetate

71
Q

T/F all nucleated cells can make cholesterol

A

TRUE

72
Q

familial hypercholesterolemia results in..

A

deposition of cholesterol

73
Q

HMG CoA reducatase catalyzes..

A

the rate liming step of cholesterol biosynthesis

74
Q

cholesterol is precursor to..

A

bile acids, steroid hormones, and vitamin D

75
Q

most plasma cholesterol is _____ (at alcohol) with fatty acid to enhance hydrophobicity

A

esterified

76
Q

T/F cholesterol is synthesized by all tissues

A

TRUE

77
Q

T/F HMG CoA reductase activity is regulated by extracellular cholesterol (LDL) in patients homozygous for FH

A

FALSE. HMG CoA reductase activity is NOT regulated by extracellular cholesterol (LDL) in patients homozygous for FH

78
Q

HMG CoA redutase activity _____ in normal cells deprived of LDL

A

increases

79
Q

addition of extracellular LDL _____ HMG CoA reductase activity in normal cells but not FH patients

A

inhibits

80
Q

what suggests a receptor for LDL?

A

high-affinity association (Kd=nM)

81
Q

LDL particles bind to surface, but _____, in some patients homozygous for FH

A

NOT internalized

82
Q

LDL receptor internalization is mediated by..

A

clathrin coated pits

83
Q

T/F cystoplasmic portion of LDL receptor has ability to bind a range of lipoprotein particles of varying size and composition

A

TRUE

84
Q

flexible linkers connect..

A

adjacent ligand binding modules

85
Q

_____ directs LDL receptor to coated pit for internalization

A

Asn-Pro-Val-Tyr

86
Q

what is required to liberate cholesterol esters?

A

lysosomal mediated degradation of LDL receptor

87
Q

what blocks LDL-dependent regulation of HMG CoA reductase (blocks acidification of lysosome)?

A

chloroquine

88
Q

delivery of cholesterol to golgi transcriptionally _____ HMG CoA reductase and LDL receptor

A

down regulates

89
Q

upon cholesterol depletion, sterol regulatory element-binding protein (SREPB) is transported to..

A

golgi

90
Q

in golgi, proteolysis occurs by _____ to generate activated transcription factor (SREBP) in nucleus, which transcriptionally up regulates LDL receptor protein, HMG CoA reductase, and genes encoding all 26 steps in cholesterol biosynthesis

A

SCAB (SREBP cleavage activating protein)

91
Q

_____ selectively inhibit HMG CoA reductase to lower plasma cholesterol

A

statins

92
Q

statins are taken up by _____ to block HMG CoA reductase

A

liver

93
Q

decreases in liver cholesterol _____ the transcription of both HMG CoA reductase and _____

A

upregulate; LDL receptors

94
Q

newly produced LDL receptors sequester additional cholesterol from _____

A

blooe

95
Q

_____ is digested and _____ is released fro liver metabolism

A

LDL; cholesterol

96
Q

statin _____ synthesis of liver cholesterol

A

prevents

97
Q

_____ maintain cholesterol necessary for liver function

A

LDL receptors

98
Q

_____ patients have large accumulation of cholesterol in lysosomes

A

Neumann-Pick C

99
Q

HDL is taken up through _____

A

receptor mediated endocytosis

100
Q

_____ disease arises from defects in NPC2 and NPC1

A

NewmanPick

101
Q

_____ and _____ work together to extract cholesterol and delivery cholesterol to membrane

A

NPC2; NPC1

102
Q

LDL receptors act to mediate….

A

transport of extracellular apolipoprotein complexes through endocytosis via clathrin coated pits

103
Q

statins are competitive inhibitors of which enzyme?

A

HMG CoA reductase

104
Q

which tissue/organ primarily takes up dietary fats carried by chylomicrons?

A

adipose tissue & muscle

105
Q

fatty acid metabolism couples to central metabolism through…

A

formation of acetyl-CoA

106
Q

all tissues, except _____ and _____, can use fatty acids as energy

A

brain and mature RBCs

107
Q

why can’t the brain use fatty acids as the blood brain barrier block transport?

A

because free fatty acids are actually bound to albumin, which is too big to cross blood-brain barrier in healthy people

108
Q

_____ have no mitochondria, and cannot metabolize acetyl-CoA

A

mature RBCs

109
Q

[LIKELY HIGH YIELD] cis-double bonds create a _____ that disrupts the acyl chain packing

A

kink

110
Q

kink acts to..

A

increase fluidity

111
Q

in fats (TAGs) kinks change the…

A

phase transition temperature

112
Q

trans-fatty acids are created as a byproduct of…

A

hydrogentation

113
Q

hydrogenation is an industrial mechanism to _____ double bonds and _____ the shelf life of fats

A

reduce; increase

114
Q

double bonds are sites of _____, as there provide a site for oxygen reactivity

A

oxidation

115
Q

_____ bonds pack very well together (have a high _____), and are often thought to be hard to metabolize and to promote artherosclerosis

A

trans-double bonds; phase transition

116
Q

biosynthesis occurs principally in…

A

cytosol

117
Q

building blocks for FA biosynthesis arises from

A

Acetyl-CoA

118
Q

only in the presence of excess _____ ( when energy needs of cellar met), is FA synthesis activated

A

citrate

119
Q

[LIKELY HIGH YIELD] what is the regulated step of FA biosynthesis?

A

acetyl CoA carboxylase

120
Q

_____ signals a fed state

A

insulin

121
Q

insulin _____ FA biosynthesis through the regulation of acetyl CoA carboxylase

A

activates

122
Q

_____ is involved in transfer of carboxylates

A

biotin

123
Q

biotin involves a _____ mechanism that moves between the 2 active sites involved in carboxylation of biotin and transfer of the carboxylate to acetyl CoA to form malonyl CoA

A

swinging arm mechanism

124
Q

biotin inolves a swinging arm mechanism that moves between the 2 active sites involved in.. (2)

A

1) carboxylation of biotin

2) transfer of the carboxylate to acetyl CoA to form malonyl CoA

125
Q

inactivation of acetyl CoA carboxylase involves..

A

AMP or phosphorylation of AMPK (AMP-activated kinase)

126
Q

AMPK i sunder the control of _____ or _____, which both indicate a need for cellular energy

A

glucagon or epinephrin

127
Q

FA biosynthesis involves enzyme FA synthase, which acts to form..

A

palmitate

128
Q

transfer of acetyl CoA is energetically _____, as the thioester bond in acetyl-CoA is maintained on the enzyme

A

favorable

129
Q

the ______ in malonyl CoA is maintained following transfer to the enzyme

A

thioester bond

130
Q

FA synthase has 7 distinct catalytic sites that permit the highly efficient catalysis of a..

A

palmitate

131
Q

insulin-dependent up regulation of lipoprotein lipase acts to..

A

shift metabolism to promote FA uptake by adipose tissue

132
Q

glycerol can be made from _____ or from _____

A

glycolytic intermediates; absorbed glycerol

133
Q

formation of ester bonds requires an activation step, which involves..

A

formation of a thirster born with CoA

134
Q

mobilization of fats is opposed by _____, which activates a phosphodiesterase that hydrolyzes cAMP

A

insulin

135
Q

_____ promotes mobilization of fats through activation of hormone sensitive lipase, which hydrolyzes a single phosphoester linkage

A

epinephrine

136
Q

where does beta oxidation o FAs occur?

A

in the mitochondrial matrix

137
Q

critical to oxidation is the regulated transfer of activated FAs which permits the transfer of the FAs to _____ for transport into the mitochondrial matrix

A

carnitine

138
Q

malonyl CoA _____ transport of FAs into the mitochondrial matrix for beta-oxidation

A

inhibits

139
Q

what is formed by the spontaneous breakdown of acetoacetic acid?

A

acetone

140
Q

acetone is _____, and is commonly smelled on breath

A

volutile

141
Q

acetoacetic acid and beta-hydroxybutryic acid are both _____ and their formation regenerates the _____ needed for further FA degradation

A

water soluble; CoA-SH

142
Q

ketones bodies are highly _____, and cross the blood brain barrier, providing a source of energy for the brain

A

soluble

143
Q

ketone bodies arise from elevations in _____

A

acetyl-CoA

144
Q

almost all ketone bodies arise from _____

A

FA degradation

145
Q

depletion of NAD+ limits ability to carry out..

A

glycolysis

146
Q

excess NADH inhibits _____ and _____

A

TCA cycle; FA oxidation

MCBM EXAM 3-Preview (18 decks)

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