Fatty Acid Catabolism Flashcards
(88 cards)
1
Q
cells can obtain fatty acid fuels from four sources:
A
- fats consumed in the diet fats
- stored in cells as lipid droplets
- fats synthesized in one organ for export to another
- fats obtained by autophagy
2
Q
Dietary Fats Are Absorbed in the Small Intestine
A
3
Q
apolipoproteins
targets:
A
proteins in their lipid-free form that bind lipids to form lipoproteins
target triacylglycerols, phospholipids, cholesterol, and cholesteryl esters for transport between organs
4
Q
chylomicrons
A
particles consisting of triacylglycerols, cholesterol, and apolipoproteins
5
Q
Storage of Excess Fatty Acids
A
- fatty acids are converted to triacylglycerols in the liver
- triacylglycerols are packaged with specific apolipoproteins into VLDLs
- VLDLs are secreted and transported in the blood to adipose tissue
- triacylglycerols are removed and stored in lipid droplets within adipocytes in the adipose tissue
6
Q
Hormones trigger mobilization of
A
stored triacylglycerols
7
Q
lipid droplets
A
organelles stored in adipocytes and steroid-synthesizing cells that contain neutral lipids
contain a core of triacylglycerols and sterol esters surrounded by a monolayer of phospholipids
8
Q
perilipins
A
family of proteins that coats the surface of lipid droplets to restrict access to the content of lipid droplets
prevent untimely lipid mobilization
9
Q
Mobilization of Triacylglycerols Stored in Adipose Tissue occurs when -
What triggers changes that open the lipd droplet to the action of three cytosolic lipases?
A
- mobilization occurs when hormones (glucagon and epinepherine) signal the need for metabolic energy
- PKA triggers changes that open the lipid droplet to the action of three cytosolic lipases
10
Q
free fatty acids, FFAs
A
fatty acids released by lipases
11
Q
serum albumin
A
blood protein that noncovalently binds and transports FFAs to target tissues
makes up ~½ of the total serum protein
12
Q
most of the biologically available energy of triacylglycerols resides in
A
their three long-chain fatty acids
13
Q
phosphorylates glycerol to form glycerol 3-phosphate in the entry of glycerol into the glycolytic pathway
A
glycerol kinase
14
Q
glyceraldehyde 3-phospbate can enter
A
glycolysis
15
Q
Fatty acids are activated and transported into
A
mitochondria
16
Q
small (< _____ carbons) fatty acids diffuse freely across mitochondrial membranes
A
<12 carbons
17
Q
Transports long-chain fatty acids (containing 14+ carbons) through the mitochondrial membrane
A
carnitine shuttle
- requires activation to a fatty acyl-CoA and
- attachment to carnitine
18
Q
fatty acyl-CoA synthetase
A
isozymes present in the outer mitochondrial membrane that activate the fatty acid by conversion to fatty acyl-CoA thioesters
fatty acid + CoA + ATP ⇄
fatty acyl-CoA + AMP + PPi
19
Q
compound that transports fatty acyl-CoAs destined for mitochondrial oxidation across the inner mitochondrial membrane
A
carnitine
20
Q
acyl-carnitine/carnitine cotransporter
A
- allows the passive transport of the fatty acyl-carnitine ester
- moves one carnitine into the intermembrane space as one fatty acyl-carnitine moves into the matrix
21
Q
_____ pools of coenzyme A located ______
A
2; cytosol and mitochondria
22
Q
coenzyme A in the mitochondrial matrix is largely used in:
A
oxidative degradation of pyruvate, fatty acids, and some amino acids
23
Q
coenzyme A in the cytosol is used in the biosynthesis of
A
fatty acids
24
Q
electron carrier that accepts electrons from FADH2
A
electron transfer flavoprotein (ETF)
25
flavoprotein that accepts electrons from ETF
ETF:ubiquinone oxidoreductase
## Footnote
passes electrons through ubiquinone into the mitochondrial respiratory chain
26
a multienzyme complex associated with the inner mitochondrial membrane that catalyzes steps 2-4 of the β-oxidation pathway for fatty acyl chains of 12+ carbons
allows efficient substrate channeling
trifunctional protein (TFP)
27
TFP is a ________ of alph4beta4 subunits
heterooctamer
## Footnote
α subunits contain enoyl-CoA hydratase and β-hydroxyacyl-CoA dehydrogenase activity
28
severe acidification of the blood and urine resulting from accumulated propionyl-CoA in the mitochondria being released to the blood as propionate
uses the carnitine shuttle
propionic acidemia
occurs in ~ 1 in 100,000 babies
29
the first intermediate of cytosolic fatty acid synthesis
blocks entry of fatty acids into mitochondria to prevent fultile cycling
malonyl-CoA
30
Oxidation of a Polyunsaturated Fatty Acid requires:
enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase
31
β oxidation in peroxisomes has four steps:
peroxisomes = organelles found in plants and animals
* dehydrogenation
* addition of water to the resulting double bond
* oxidation of the β-hydroxyacyl-CoA to a ketone
* thiolytic cleavage by coenzyme A
32
characterized by an inability to make peroxisomes
individuals lack all metabolism related to peroxisomes
Zellwger syndrome
33
characterized by the inability of peroxisomes to oxidize very-long-chain fatty acids
due to the lack of a functional transporter in the peroxisomal membrane
X-linked adrenoleukodystrophy (XALD)
34
a long-chain fatty acid with methyl branches that is derived from the phytol side chain of chlorophyll
the methyl group on the β carbon makes β oxidation impossible
phytanic acid
35
refsum disease
results from a genetic defect in phytanoyl-CoA hydroxylase
36
catalyzes the oxidation of D-β-hydroxybutyrate to acetoacetate in extrahepatic tissue
D-β-hydroxybutyrate dehydrogenase
37
Ketone bodies are used as fuel in all tissues except
liver
## Footnote
the liver lacks β-ketoacyl-CoA transferase
the liver is a producer of ketone bodies, not a consumer
38
α oxidation
removes a single carbon from the carboxyl end of the fatty acid
converts branched fatty acids to products that can undergo β oxidation to yield acetyl-CoA and propionyl-CoA
39
Two pools of fatty acyl-CoA
One pool is in the _______ and the other is in \_\_\_\_\_\_\_\_\_\_
cytosol; mitochondria
40
fatty acyl-CoA in the mitochondrial matrix can be used for
oxidation and ATP production
conversion to the carnitine ester commits it to oxidation
41
fatty acyl-CoA in the cytosolic pool can be used for
membrane lipid synthesis
42
the rate-limiting step for oxidation of fatty acids in mitochondria
carnitine-mediated entry (carnitine shuttle)
43
inhibits carnitine acyltransferase 1 and prevents the simultaneous synthesis and degradation of fatty acids
malonyl-CoA, the first intermediate in fatty acid synthesis
44
Step 1 of Fatty Acid Oxidation
β oxidation
fatty acids undergo oxidative removal of successive two-carbon units in the form of acetyl-CoA
45
Stage 2 of Fatty Acid Oxidation
* oxidation of acetyl-CoA groups to CO2 in the citric acid cycle
* occurs in the mitochondrial matrix
* generates NADH, FADH2, and one GTP
46
Stage 3 of Fatty Acid Oxidation
electron transfer chain and oxidative phosphorylation
generates ATP from NADH and FADH2
47
flavoprotein with tightly bound FAD that catalyzes the dehydrogenation of fatty acyl-CoA to yield a trans-∆2-enoyl-CoA
acyl-CoA dehydrogenase
48
Acyl-CoA Dehydrogenase Isozymes
* isozymes are specific for fatty-acyl chain lengths:
* VLCAD (inner mitochondrial matrix): 12-18 carbons
* MCAD (matrix): 4-14 carbons
* SCAD (matrix): 4-8 carbons
49
Hydration of the Trans-∆2-Enoyl-CoA
\_\_\_\_\_\_\_\_\_catalyzes the addition of water to the double bond of the trans-∆2-enoyl-CoA to form….
enoyl-CoA hydratase
...L-β-hydroxyacyl-CoA (3-hydroxyacyl-CoA)
50
catalyzes the dehydrogenation of L-β-hydroxyacyl-CoA
….to form
β-hydroxyacyl-CoA dehydrogenase
...
β-ketoacyl-CoA
enzyme is specific for the L stereoisomer
51
NADH dehydrogenase (Complex I)
electron carrier of the respiratory chain
accepts electrons from the NADH formed in the β-hydroxyacyl-CoA dehydrogenase reaction
52
catalyzes the reaction of β-ketoacyl-CoA with free coenzyme A to yield….
acyl-CoA acetyl-transferase (thiolase)
...acetyl CoA and a fatty acyl-CoA shortened by two carbons
53
β subunits contain ______ activity
thiolase activity
54
The Four β-Oxidation Steps Are Repeated to yield
Acetyl-CoA and ATP
55
The Overall Reaction for Stage 1 of
β Oxidation
palmitoyl-CoA + 7CoA + 7FAD + 7NAD+ + 7H2O ⟶
8 acetyl-CoA + 7FADH2 + 7NADH + 7H+
56
each FADH2 donates a pair of electrons to ETF
generates -
each NADH donates a pair of electrons to the mitochondrial NADH dehydrogenase
generates -
in total, _______ are formed for each pass through Beta oxidation
FADH2 - 1.5 molecules of ATP
NADH - 2.5 molecules of ATP
4 ATP are formed
57
The Overall Reaction for Stage 1 of
β Oxidation, Including Electron Transfers and Oxidative Phosphorylations
palmitoyl-CoA + 7CoA + 7O2 + 28Pi + 28ADP ⟶
8 acetyl-CoA + 28ATP + 7H2O
58
The Overall Reaction for the Complete Oxidation of Palmitoyl-CoA to CO2 and H2O
palmitoyl-CoA + 23O2 + 108Pi + 108ADP ⟶
CoA + 108ATP + 16CO2 + 23H2O
59
enoyl-CoA hydratase cannot catalyze the addition of H2O to a cis double bond
oxidation of unsaturated fatty acids requires two additional enzymes:
* enoyl-CoA isomerase (converts cis double bonds to trans)
* 2,4-dienoyl-CoA reductase (reduces cis double bonds)
60
acetone, acetoacetate, and D-β-hydroxybutyrate
formed from acetyl-CoA in the liver
ketone bodies
## Footnote
acetoacetate and D-β-hydroxybutyrate are transported to extrahepatic tissues and converted to acetyl-CoA to be oxidized in the citric acid cycle
61
oxidation of a monounsaturated fatty acid requires
an enoyl-CoA isomerase
62
isomerizes the cis-∆3-enoyl-CoA to the trans-∆2-enoyl-CoA
∆3,∆2- enoyl-CoA isomerase
63
beta oxidation requires double bond between
C2 and C3
64
Complete oxidation of odd-number fatty acids require \_\_\_\_\_\_\_extra reactions
three
65
three-carbon compounds formed by cattle and other ruminant animals during carbohydrate fermentation
propionate (CH3–CH2–COO−)
66
odd-number fatty acids are oxidized by the β-oxidation pathway to yield acetyl-CoA and a molecule of
propionyl-CoA
67
\_\_\_\_\_catalyzes the carboxylation of propionyl-CoA to form D-methylmalonyl-CoA
cofactor:
propionyl-CoA carboxylase
## Footnote
requires the cofactor biotin
68
Oxidation of Propionyl-CoA Step 2
\_\_\_\_\_\_\_\_\_\_catalyzes the epimerization of D-methylmalonyl-CoA to its L stereoisomer
methylmalonyl-CoA epimerase
69
Oxidation of Propionyl-CoA – Step 3
\_\_\_\_\_\_\_\_\_catalyzes the intramolecular rearrangement of L-methylmalonyl-CoA to form succinyl-CoA (which can enter the citric acid cycle)
requires:
methylmalonyl-CoA mutase
requires: 5′-deoxyadenosylcobalamin, or coenzyme B12, as its coenzyme
70
catalyzes the enzymatic condensation of two acetyl-CoA molecules to form acetoacetyl-CoA
reversal of the last step of β oxidation
thiolase
71
Transcription factors turn on the synthesis of proteins for \_\_\_\_\_\_\_\_\_\_
lipid catabolism
72
transcription factors that affect many metabolic processes in response to a variety of fatty acid–like ligands
PPAR family of nuclear receptors
73
stimulates the synthesis of enzymes required in β oxidation when there is an increased demand for energy from fat catabolism
PPARα
74
acyl-CoA dehydrogenase isozyme that acts on fatty acids of 4-14 carbons
medium-chain acyl-CoA dehydrogenase (MCAD)
75
individuals with two mutant MCAD alleles cannot oxidize fatty acids of\_\_\_\_\_\_\_
symptoms includes:
6-12 carbons
## Footnote
symptoms include fatty liver, high blood levels of octanoic acid (8:0), coma, and death
76
Other Genetic Defects in Fatty Acid Transport or Oxidation
* loss of the long-chain β-hydroxyacyl-CoA dehydrogenase activity of the trifunctional protein, TFP
* defects in the α or β subunits that affect all three activities of TFP
77
catalyzes the condensation of acetoacetyl-CoA with acetyl-CoA to form β-hydroxy-β-methylglutaryl-CoA (HMG-CoA)
HMG-CoA synthase
78
Differences Between the Peroxisomal and Mitochondrial Pathways
in peroxisomes, the flavoprotein acyl-CoA oxidase that introduces the double bond passes electrons directly to O2, producing H2O2
the enzyme catalase cleaves H2O2 to H2O and O2
the peroxisomal system is much more active on very-long-chain fatty acids and branched-chain fatty acids
79
catalyzes the cleavage of HMG-CoA to free acetoacetate and acetyl-CoA
HMG-CoA lyase
80
catalyzes the decarboxylation of acetoacetate to aceton
acetoacetate decarboxylase
81
catalyzes the reversible reduction of acetoacetate to D-β-hydroxybutyrate
D-β-hydroxybutyrate dehydrogenase
82
catalyzes the activation of acetoacetate
β-ketoacyl-CoA transferase
acetyl-CoA enters the citric acid cycle
83
Ketone Bodies are Overproduced in _______ and during \_\_\_\_\_\_\_\_
Diabetes; starvation
## Footnote
the accumulation of acetyl-CoA accelerates formation of ketone bodies
extrahepatic tissues do not have the capacity to oxidize them all
84
lowered blood pH
can be caused by increase levels of acetoactate, and D-β-hydroxybutyrate
acidosis
85
high levels of ketone bodies in the blood and urine
ketosis
86
condition when ketosis and acidosis are combined
ketoacidosis
87
Individuals with untreated diabetes have high _______ levels
acetone
## Footnote
individuals with untreated diabetes produce large quantities of acetoacetate
acetone formed from the decarboxylation of acetoacetate is volatile
imparts a characteristic odor to the breath
88
catalyzes the decarboxylation of acetoacetate to acetone
acetoacetate decarboxylase
