WK1_5 Alternative Fatty Acid Oxidation / Fatty Acid Synthesis and Metabolism Flashcards
fatty acid (FA) metabolism couples to central metabolic pathways through..
Acetyl-CoA
free fatty acids (FA) can be taken up by most tissue and used as energy source except.. (2)
brain and RBCs
greater 90% of FA in plasma are esters (_____, _____, and ______)
TAGs, cholesterol esters, phospholipids
does saturated FA have double bonds?
no
does unsaturated FA have double bonds?
yes
between the 2 double bonds present in unsaturated FA, which one is natural?
cis
trans double bonds are produced as by-product of _____
hydrogenation
which double bond is solid at body temperature?
trans
in FA nomenclature, carboxylate is numbered as carbon #_
1
in FA nomenclature, number before colon represents..
length of chain
in FA nomenclature, number after colon represents..
how many double bonds
in FA nomenclature, numbers in parentheses represents..
positions in unsaturation
carbon at methyl terminus is the ______ carbon
omega
FA biosynthesis occurs primarily in the..
liver cytosol
T/F mitochondrial Acetyl-CoA cannot be exported to the cytosol
TRUE
acetyl moiety enters ctyosol as _____ following condensation with oxaloacetate
citrate
acetyl moiety enters cytosol as citrate following..
condensation with oxaloacetate
regulation of transport is via [?], which is high under the fed state
[citrate]
regulation of transport is via [citrate], which is high under the _____ state
fed state
during fed state, large amounts of ATP inhibit _____ in TCA cycle
isocitrate dehydrogenase
oxaloacetate is transported back into _____ through transporters, permuting efficient cycle of transfer of acetate into cytosol
mitochondrila matrix
regulation of fatty acid biosynthesis is through..
Acetyl-CoA carboxylase
biotin mediates carboxylation of acetyl ova through a ______ type of mechanism
swinging arm
insulin activates through…
phosphatase activation
insulin activates through phosphatase activation (______)
fed state
insulin-dependent activation of Acetyl-CoA carboxylase ______ fatty acid biosynthesis
upregulates
FA synthesis occurs in the ______ and uses ______
cytosol; NADPH (not NADH)
FA is cleaved by..
palmitoyl thiesterase
further ______ and ______ of FA occurs in smooth ER
elongation; desaturation
carbon skeleton rearrangements set enzyme up for next..
condensation
2 carbon acetate condenses with Malonyl-CoA, with release of..
carbon dioxide
______ enhances availability of extracellular fatty acids to permit adipose tissue uptake and formation of TAGs
insulin
LPL _____ FA on TAGs in chylomicrons
hydrolyzes
______ transport FA
adipocytes
______ is basic building bock for TAG synthesis
glycerol
in _____, glycerol kinase phosphorylates glycerol released following delivery of FA to adipose tissue
liver
synthesis of TAG involves activation of FA by _____ and _____
CoA-SH; sequential condensation
_____ mobilizes fats (TAGs) in adipose tissue
epinephrine
_____ blocks lipolysis through activation of phosphodiesterase (hydrolysis of cAMP) to enhance synthesis of fats
insulin
mobilization of FA reserves in adipocytes is initiated by _____
hormone sensitive lipase
hormonal activation of cAMP-dependent protein kinase through _____
adenylate cyclase
phosphorylation of lipase initiates TAG _____
degradation
phosphorylation of acetyl CoA carboxylase _____ FA synthesis
inhibits
glycerol is released and transported to liver for _____
reuptake
FA transported to tissues in complex with..
albumin
beta oxidation of fatty acids occurs in ______
mitochondrial matrix
FA is activated by conjugation with..
HS-CoA
what kind of molecule is carnitine?
carrier molecule
FA acyl chain is transferred to carnitine by..
carnitine palmitoyl transferase
malonyl CoA _____ carnitine palmitoyl transferase preventing FA synthesis from occurring simultaneously as oxidation
inhibits
net production of _____ ATP per palmitate oxidized
129
formation of ketone bodies arise from elevations in..
lacetyl-CoA
where does ketone body formation occur?
in liver
formation of CoA allows..
FA oxidation
ethanol metabolism involves formation of _____, and can deplete _____ needed for glycolysis
NADH; NAD+
excess NADH causes metabolic disorders, including inhibition of _____ and _____
TCA cycle; FA oxidation
accumulation of FA in liver can result in fatty liver (_____)
steatosis
metabolism of ethanol results in large increases in..
NADH
_____ is _inhibited due to depletion of oxaloacetate
TCA cycle
_____ is inhibited due to depletion of pyruvate
gluconeogenesis
_____ is inhibited due to depletion of NAD+
glycolysis
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
C: stearic acid has 18 carbons and fully reduced
what molecule acts as the carbon carrier to move acetyl CoA across the mitochondrial membrane for fatty acid biosynthesis?
citrate
which cofactor/vitamin is used to transfer carboxylate moieties?
biotin
which apolipoprotein acts to transport lipids from the liver to peripheral tissues?
VLDL
alcoholism typically requires consumption of 30-50% of total calories as ethanol, and is commonly associated with increases in which metabolite?
ketone bodies + NADH
what are the functions of cholesterol?
- structural component in membranes
- precursor of bile acids/steroid hormones/vitamin D
what are the regulations of cholesterol?
- liver plays central role in regulating cholesterol availability
- cholesterol precipitates along endothelial lining of blood vesicles (plaque formation ) contributing to cardiovascular disease
_____ catalyzes rate limiting step of cholesterol biosynthesis
HMG CoA reductase
_____ provides all carbons for cholesterol biosynthesis
acetate
T/F all nucleated cells can make cholesterol
TRUE
familial hypercholesterolemia results in..
deposition of cholesterol
HMG CoA reducatase catalyzes..
the rate liming step of cholesterol biosynthesis
cholesterol is precursor to..
bile acids, steroid hormones, and vitamin D
most plasma cholesterol is _____ (at alcohol) with fatty acid to enhance hydrophobicity
esterified
T/F cholesterol is synthesized by all tissues
TRUE
T/F HMG CoA reductase activity is regulated by extracellular cholesterol (LDL) in patients homozygous for FH
FALSE. HMG CoA reductase activity is NOT regulated by extracellular cholesterol (LDL) in patients homozygous for FH
HMG CoA redutase activity _____ in normal cells deprived of LDL
increases
addition of extracellular LDL _____ HMG CoA reductase activity in normal cells but not FH patients
inhibits
what suggests a receptor for LDL?
high-affinity association (Kd=nM)
LDL particles bind to surface, but _____, in some patients homozygous for FH
NOT internalized
LDL receptor internalization is mediated by..
clathrin coated pits
T/F cystoplasmic portion of LDL receptor has ability to bind a range of lipoprotein particles of varying size and composition
TRUE
flexible linkers connect..
adjacent ligand binding modules
_____ directs LDL receptor to coated pit for internalization
Asn-Pro-Val-Tyr
what is required to liberate cholesterol esters?
lysosomal mediated degradation of LDL receptor
what blocks LDL-dependent regulation of HMG CoA reductase (blocks acidification of lysosome)?
chloroquine
delivery of cholesterol to golgi transcriptionally _____ HMG CoA reductase and LDL receptor
down regulates
upon cholesterol depletion, sterol regulatory element-binding protein (SREPB) is transported to..
golgi
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
SCAB (SREBP cleavage activating protein)
_____ selectively inhibit HMG CoA reductase to lower plasma cholesterol
statins
statins are taken up by _____ to block HMG CoA reductase
liver
decreases in liver cholesterol _____ the transcription of both HMG CoA reductase and _____
upregulate; LDL receptors
newly produced LDL receptors sequester additional cholesterol from _____
blooe
_____ is digested and _____ is released fro liver metabolism
LDL; cholesterol
statin _____ synthesis of liver cholesterol
prevents
_____ maintain cholesterol necessary for liver function
LDL receptors
_____ patients have large accumulation of cholesterol in lysosomes
Neumann-Pick C
HDL is taken up through _____
receptor mediated endocytosis
_____ disease arises from defects in NPC2 and NPC1
NewmanPick
_____ and _____ work together to extract cholesterol and delivery cholesterol to membrane
NPC2; NPC1
LDL receptors act to mediate….
transport of extracellular apolipoprotein complexes through endocytosis via clathrin coated pits
statins are competitive inhibitors of which enzyme?
HMG CoA reductase
which tissue/organ primarily takes up dietary fats carried by chylomicrons?
adipose tissue & muscle
fatty acid metabolism couples to central metabolism through…
formation of acetyl-CoA
all tissues, except _____ and _____, can use fatty acids as energy
brain and mature RBCs
why can’t the brain use fatty acids as the blood brain barrier block transport?
because free fatty acids are actually bound to albumin, which is too big to cross blood-brain barrier in healthy people
_____ have no mitochondria, and cannot metabolize acetyl-CoA
mature RBCs
[LIKELY HIGH YIELD] cis-double bonds create a _____ that disrupts the acyl chain packing
kink
kink acts to..
increase fluidity
in fats (TAGs) kinks change the…
phase transition temperature
trans-fatty acids are created as a byproduct of…
hydrogentation
hydrogenation is an industrial mechanism to _____ double bonds and _____ the shelf life of fats
reduce; increase
double bonds are sites of _____, as there provide a site for oxygen reactivity
oxidation
_____ bonds pack very well together (have a high _____), and are often thought to be hard to metabolize and to promote artherosclerosis
trans-double bonds; phase transition
biosynthesis occurs principally in…
cytosol
building blocks for FA biosynthesis arises from
Acetyl-CoA
only in the presence of excess _____ ( when energy needs of cellar met), is FA synthesis activated
citrate
[LIKELY HIGH YIELD] what is the regulated step of FA biosynthesis?
acetyl CoA carboxylase
_____ signals a fed state
insulin
insulin _____ FA biosynthesis through the regulation of acetyl CoA carboxylase
activates
_____ is involved in transfer of carboxylates
biotin
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
swinging arm mechanism
biotin inolves a swinging arm mechanism that moves between the 2 active sites involved in.. (2)
1) carboxylation of biotin
2) transfer of the carboxylate to acetyl CoA to form malonyl CoA
inactivation of acetyl CoA carboxylase involves..
AMP or phosphorylation of AMPK (AMP-activated kinase)
AMPK i sunder the control of _____ or _____, which both indicate a need for cellular energy
glucagon or epinephrin
FA biosynthesis involves enzyme FA synthase, which acts to form..
palmitate
transfer of acetyl CoA is energetically _____, as the thioester bond in acetyl-CoA is maintained on the enzyme
favorable
the ______ in malonyl CoA is maintained following transfer to the enzyme
thioester bond
FA synthase has 7 distinct catalytic sites that permit the highly efficient catalysis of a..
palmitate
insulin-dependent up regulation of lipoprotein lipase acts to..
shift metabolism to promote FA uptake by adipose tissue
glycerol can be made from _____ or from _____
glycolytic intermediates; absorbed glycerol
formation of ester bonds requires an activation step, which involves..
formation of a thirster born with CoA
mobilization of fats is opposed by _____, which activates a phosphodiesterase that hydrolyzes cAMP
insulin
_____ promotes mobilization of fats through activation of hormone sensitive lipase, which hydrolyzes a single phosphoester linkage
epinephrine
where does beta oxidation o FAs occur?
in the mitochondrial matrix
critical to oxidation is the regulated transfer of activated FAs which permits the transfer of the FAs to _____ for transport into the mitochondrial matrix
carnitine
malonyl CoA _____ transport of FAs into the mitochondrial matrix for beta-oxidation
inhibits
what is formed by the spontaneous breakdown of acetoacetic acid?
acetone
acetone is _____, and is commonly smelled on breath
volutile
acetoacetic acid and beta-hydroxybutryic acid are both _____ and their formation regenerates the _____ needed for further FA degradation
water soluble; CoA-SH
ketones bodies are highly _____, and cross the blood brain barrier, providing a source of energy for the brain
soluble
ketone bodies arise from elevations in _____
acetyl-CoA
almost all ketone bodies arise from _____
FA degradation
depletion of NAD+ limits ability to carry out..
glycolysis
excess NADH inhibits _____ and _____
TCA cycle; FA oxidation
