MBOD Block 4 Week 3 Flashcards
(194 cards)
3
Q
Where are fats primarily stored?
A
In adipose tissue
4
Q
How are fatta acids oxidized?
A
By B-oxidation pathway in mitochondria
5
Q
What is the path of dietary fatty acids?
A
They are carried from the intestine to tissues to be metabolized as part of chylomicrons.
6
Q
What is the path of stored fatty acids?
A
They are released from storage (lipolysis), and transported bound to serum albumin to be oxidized.
7
Q
Which bond is cleaved in B-oxidation?
A
The alpha-beta bond.
8
Q
What is Linolenate?
A
An 18 C FA with 3 double bonds (polyunsaturated); omega-3,6,9FA; Can also be called a cis delta-9,12,15 Octadecatrienoate.
9
Q
Where do glucose and triglycerides from the diet or from the liver release go?
A
To make TG.
10
Q
What are the stores of TG released as upon hormonal signals?
A
FA + Glycerol.
11
Q
What do lipolytic hormones do?
A
Increases adipocyte cAMP and activation of lipase. Serum free fatty acid levels increase.
12
Q
What are some lipolytic hormones?
A
Glucagon and Epinephrine
13
Q
What is a antilipolytic hormone?
A
Decreases adipocyte cAMP. Decreased serum free fatty acid (FFA).
14
Q
What is the major antyilipolytic hormone?
A
Insulin
15
Q
What does a lack of insulin result in, esp in Type 1 diabetes?
A
Excessive lipolysis leading to ketoacidosis.
16
Q
How do FA come into the muscle cell?
A
Carried on FA-albumin in the blood after the release by fat.
17
Q
What are the activated transport intermediates in mitochondrial long-chain FA metabolism.
A
FACoA and FA carnitine
18
Q
What are FACoA in the mitochondrial matrix oxidized to?
A
FAD2H, NADH, and AcCoA, which feed into the TCA and ETC or are made into Ketone bodies
19
Q
How many carbons are in a short chain FA?
A
2-4
20
Q
What type of membrane transport do short chain FA use?
A
Free diffusion
21
Q
What type of membrane transport do medium chain FA use?
A
Diffusion
22
Q
How many carbons are in a medium chain FA?
A
4-12
23
Q
How many carbons are in a long chain FA?
A
12-20
24
Q
What type of membrane transport do long chain FA use?
A
Carnitine cycle
25
Q
What is the site of catabolism for very long chain FA?
A
Peroxisome
26
Q
How many carbons are in a very long chain FA?
A
> 20
27
What are the metabolic routes for Fatty acyl CoA?
Energy, Membrane lipids, Storage
28
What is the role of Carnitine?
It carriers FA bound to it into the mitochondria.
29
What are the enzymes that reversibly transfer FACoA and FAcarnitine?
CPT1 and CPT2 (Carnitine palmitoyl-transferase I and II)
30
What facilitates the exchange of carnitine and acyl-carnitine?
Carnitine acylcarnitine Translocase
31
What is the first step of B-oxidation and the enzyme used?
Oxidize to double bond. Acyl CoA Dehydrogenase
32
What is the product of the first step of B-oxidation?
trans Fatty enoyl CoA
33
What is the second step of B-oxidation and the enzyme used?
Hydration adds -OH and -H across bond. Enoyl CoA hydratase
34
What is the product of the second step of B-oxidation?
L-B-Hydroxy acyl CoA
35
What is the third step of B-oxidation and the enzyme used?
Oxidize to double bond; C-OH=>C=O. B-hydroxy Acyl CoA Dehydrogenase
36
What is the product of the third step of B-oxidation?
B-Keto acyl CoA
37
What is the fourth step of B-oxidation and the enzyme used?
Cleaved (thiolysis). B-keto thiolase
38
What is the product of the fourth step of B-oxidation?
2 C shorter FACoA and AcCoA.
39
What are the similar processes between B-oxidation and the CAC?
Hydration, production of FADH2 and NADH
40
Where do the electrons from fatty acid oxidation go to; and what are the enzymes used?
The ETC. Acyl CoA dehydrogenase, Electron transferring flavoprotein (ETF), ETF-CoQ oxidoreductase.
41
How much does 1 palmitate undergoing 7 cycles of B-oxidation yield?
7 FADH2, 7NADH, 8AcCoA
42
How many ATP are produced by the 7FADH2 and 7 NADH?
28 ATP
43
How many ATP are produced by 8 AcCoA?
80 ATP
44
What is the net ATP yield from B-Oxidation?
106 ATP/palmitate
45
What is CPT1 inhibited by?
Malonyl CoA
46
What is the major control of FA oxidation?
Availability of FA
47
What occurs with oxidation of unsaturated FA?
The unconjugated double bonds are moved so that it becomes a conjugated double bond in the trans configuration.
48
What prevents double bonds from interferring with B-oxidation?
The isomerase and reductase working together.
49
What is the product of odd-chain FA oxidation?
Propinyl CoA and Acetyl CoA
50
What forms propionyl CoA?
The final thiolysis step in the oxidation of odd chain FA.
51
What are the two vitamins that are required for the metabolism of Propionic Acid?
Biotin and B12
52
What is the end product of the metabolism of Propionic Acid?
Succinyl CoA ->to CAC
53
What is Zellweger syndrome?
Lack of functional peroxisomes; defective import of proteins; VLCFA acumulate; liver kidney, and muscle damage.
54
What is formed from the oxidation of VLCFAs?
H2O2 and NADH
55
How long does the peroxisome oxidation of VLCFA repeat until?
Until there are 6-10 Carbons.
56
What is the result of Alpha-oxidation of branched chain FA?
PropCoA or AcCoA; repeats until the chain is 8C.
57
What does the branched chain FA that has been oxidized go to the mitochondria as?
FA-carnitine
58
What is Refsun's Disease?
A rare neurological disorder caused by defective alpha-oxidation. Phytanic acid is deposited in nerve tissue.
59
What does omega-oxidation convert FA to?
Dicarboxylic acids
60
What is the fate of dicarboxylic acids after omega-oxidation?
They may be excreted or conjugated to glycine or carnitine.
61
What is the treatment for disorders of FA Oxidation?
Avoid fasting; more smaller meals; less fat; provide energy needs with carbs-controls lipolysis and decreases dependence on fats and ketones for energy.
62
What does the B-oxidation of "even chain" FA in the mitohondria produce?
AcCoA, FADH2, and NADH
63
What does the B-oxidation of "odd chain" FA in the mitohondria produce?
FADH2, NADH, AcCoA, and propionyl CoA ->succinyl CoA
64
What does the B-oxidation of unsaturated FA in the mitohondria require?
Two extra enzymes, an isomerase and a reductase to modify the double bonds.
65
What do peroxisomes specialize in?
Very long and long-chain fatty acids (n>8).
66
What do peroxisomes produce?
AcCoA, FADH2, and H2O2.
67
What are branched-chain phytanic acids oxidized by?
Alpha-oxidation
68
What does alpha-oxidation do?
It removes one carbon from the carboxyl end.
69
What does B-oxidation alternately release in peroxisomes when dealing with branched-chain phytanic acids?
AcCoA and Propionyl CoA until the chain reaches 8 C, then it leaves the peroxisome as fatty acyl-carnitine.
70
Where does omega-oxidation occur?
In the ER.
71
What can accumulate abnormally in omega oxidation if B-oxidation is defective?
Dicarboxylic acids
73
What is the main thing that is occuring in the Fed State?
Glucose, FA, AA is used for fuel or stored.
74
What is the main thing that is occuring in the Fasted State?
Fat starts breaking down TG to FA and glycerol
75
What is the main thing that is occuring in the Basal Fasted State?
Fat releases FA which is used for energy and Ketone Body synthesis.
76
What is the main fuel source in the Starved State?
FA
77
Whatbecomes fuel for the brain in the Starved State?
KB
78
What are the key fuels in the fasting state?
Ketones
79
Where is HMG CoA synthase found?
In liver mitochondria
80
Where are ketones only made?
In the liver
81
What are the ketone bodies made in liver and metabolized in muscle, brain, etc.
Acetoacetate and B-hydroxybutyrate
82
What can acetoacetate be spontaneously decarboxylated to?
Acetone
83
What is the first step in ketone synthesis?
Two acetyl CoA condense to produce Acetoacetyl CoA.
84
What is the condensation of 2 Acetyl CoA catalyzed by?
Thiolase
85
What is the second step in ketone synthesis?
Acetoacetyl CoA and Acetyl CoA form HMG CoA
86
What catalyzes the formation of HMG CoA in ketone synthesis?
HMG CoA synthase
87
T/F The Liver can use ketones.
False
88
What is the third step in ketone synthesis?
HMG CoA is cleaved by HMG CoA lyase to form acetyl CoA and Acetoacetate.
89
What can acetoacetate be reduced to and by what enzyme?
B-Hydroxybutyrate; by B-hydroxybutyrate dehydrogenase. (reversible reaction)
90
How is acetone excreted?
Via the lungs
91
How can acetone be detected in the body?
By its odor - ketone breath
92
When can ketones partially replace glucose as fuel?
During fasting and starvation
93
What can acetoacetate and B-hydroxybutyrate affect in the body?
They can affect pH (ketoacidosis) and enter the urine (ketonuria), and cause extreme ketone body concentration (Ketosis). Can cause coma and death.
94
What is the key factor in the control of ketone synthesis?
Availability of FA
95
How is ketone synthesis regulated?
High NADH depletes OAA to help shunt AcCoA to make ketone bodies because less OAA is available for citrate.
97
What are the steps during pyruvate oxidation where NADH is produced?
Pyruvate dehydrogenase; isocitrate dehydrogenase; alpha-ketoglutarate dehydrogenase; malate dehydrogenase
98
What is the step in pyruvate oxidation where FADH2 is formed?
Succinate dehydrogenase
99
What do NADH and FADH2 give up to the ETC?
Their protons and electrons.
100
What creates a gradient across the mitochondrial inner membrane?
The pumping of protons by the protein complexes.
101
What is used as a source of energy to generate ATP by the ATP synthase?
The proton gradient.
102
What is the final step in the electron transport process?
Export of the newly formed ATP out of the mitochondrion to the cytosol where it can be used for synthesis, transport, etc.
103
When electrons move spontaneously between two compounds, which direction do they move?
In the direction that releases free energy.
104
Where do the electrons in NADH and FADH2 have a tendency to move?
To more positive reduction potentials and release free energy as they move.
105
How is the free energy of the electrons conserved in a chemical and electrical gradient?
By pumping the protons out of the matrix across the inner membrane.
106
What is Complex I of the ETC?
NADH Dehydrogenase complex
107
What are the two domains that complex I is composed of?
The membrane arm and the peripheral arm.
108
What does the peripheral arm of Complex I contain?
Most of the redox active centers.
109
What does the membrane arm of complex I contain?
All of the mitochondrially encoded subunits.
110
What is the inhibitor of complex I?
Rotenone
111
How does Rotenone inhibit complex I?
It binds to complex I and competes at one of the ubiquinone binding sites. Electron transfer from complex I is blocked.
112
What is the stoichiometry of protons pumped to electrons transferred?
4 protons to 2 electrons
113
How many electrons are passed for each NADH oxidized?
two
114
What are the three subunits in the membrane domain of complex I?
NuoM, NuoN, and NuoL; proton translocating subunits.
115
How many protons per pair of electrons does complex I pump?
Four
116
What are iron-sulfur centers?
Redox active ceners that can accept and then donate electrons in the electron transfer pathway.
117
What are the different varieties of the iron-sulfur clusters?
2Fe-2S; 4Fe-4S cluster; a 1Fe center coordinated with four cysteines; 3Fe-4S cluster
118
What do iron-sulfur clusters act as a conduit for?
For the electrons to travel from the FMN to ubiquinone.
119
What is FMN?
A cofactor tightly bound to the peripheral arm of complex I. (Flavin mononucleotide)
120
What are the four flavoproteins that feed electrons to ubiquinone?
Complex I, Complex II, Electron transfer flavoprotein dehydrogenase, sn-glycerophosphate dehydrogenase (an NADH shuttle)
121
What is the common thing among the flavoproteins?
The flavin gets the electrons first and then passes them on to the iron-sulfur centers.
122
What is the role of NADH in the ETC?
It is an obligatory 2 electron donor.
123
What is the role of Fe3+ in the ETC?
It is an obligatory one electron acceptor.
124
What is complex II?
A tetramer of non-identical subunits. It contains FAD and three iron sulfur clusters.
125
What is the only TCA cycle enzyme that is an integral membrane protein.
Succinate dehydrogenase
126
What does complex II consist of?
A tetramer of non-identical subunits. It contains FAD and three iron sulfur clusters. Two small hydrophobic membrane subunits with a heme sandwiched between the subunits.
127
What flavoprotein is part of the glycerophosphate shuttle for moving electrons from cytosolic NADH inot the electron transfer pathway?
Sn-glycerophosphate dehydrogenase.
128
What reaction does glycerophosphate dehydrogenase perform?
It converts dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate.
129
In which cells are levels of the mitochondrial form of the glycerol 3-phosphate dehydrogenase high?
Pancreatic islet cells.
130
What protein might be a candidate gene involved in patients with non-insulin dependent diabetes mellitus (NIDDM)?
Glycerol 3-phosphate dehydrogenase (levels are low)
131
What is ubiquinone?
A lipid soluble electron carrier that carries electrons between complexes in the electron transport pathway.
132
How many electrons can ubiquinone accept at a time?
One
133
What is ubiquinone called when it has accepted only one electron?
A semiquinone.
134
What is the state of ubiquinone when it has two electrons?
It is fully reduced.
135
What is the state of ubiquinone when it has no electrons?
It is fully oxidized.
136
How os the semiquinone stabilized?
By binding to protein sites.
137
What is another name for complex III?
The bc1 complex.
138
What are the extra subunits of complex III called that have no known function?
Supernumerary subunits.
139
What are the redox centers that you must know to understand complex III?
Two b type hemes that are contained in the same subunit and are directly above one another in the membrane and perpendicular to the membrane.
140
What is the mechanism that complex III operates by?
The Q cycle.
141
Where does the ubiquinone become oxidized?
At center P or the oxidation center.
142
What two paths are the two electrons of ubiquinone split into?
The Rieske iron sulfur center and the first b heme called BL.
143
Which path would the electrons prefer to choose?
The pathway toward the most positive reduction potential - to the iron-sulfur center.
144
What is the structure that forces the splitting of the electrons?
The bc1 complex.
145
What is the path of the electron that goes from the iron-sulfur center?
It goes to cytochrome c1 and is finally passed on to cytochrome c; it is used to reduce oxygen in complex IV, cytochrome c oxidase.
146
What is the path of the other non-productive electron from the first b heme BL?
It passes on to the second b heme BH and is given to a fully oxidized ubiquinone at the N center or reduction center.
147
What is the net movement of protons for every two ubiquinones that get oxidized?
4 out at the cytosol and two in from the matrix
148
How does Antimycin act as an inhibitor to complex III/bc1 complex?
It binds very tightly to the N center at the matrix side of the membrane and prevents electrons from reaching unbiquinone from the b hemes.
149
What binds at the P center and prevents entry of the loosely bound ubiquinone and stops electron flow through the complex?
Stigmatellin
150
How many electrons does it take to reduce oxygen?
4
151
What is charge compensation?
To take up a proton to compensate for the cost of using a electron. May be part of the driving force for proton pumping.
152
What are the redox centers in cytochrome c oxidase?
Copper A and copper B.
153
What are the contents of Copper A?
Two coper ions near one another; two hemes of the a type-heme a and heme a3; a magnesium ion and a zinc ion.
154
Where is the first place the electron goes upon leaving cytochrome c?
The copper A site.
155
What forms the binuclear center in cytochrome c?
Heme a3 and copper B
156
What forms a supercomplex?
Complex I, a dimer of complex II and complex IV.
157
What does the supercomplex facilitate?
It allows efficient transfer of electrons down the pathway.
159
What is ATP synthase?
A molecular motor that synthesizes ATP using the energy stored in the proton and membrane potential gradient.
160
What does the F1 part of ATPase contain?
The catalytic subunits
161
What does the Fo part of ATPase contain?
The proton channel; the stalk and 10 c subunits.
162
What happens when ATP synthesis is said to be uncoupled from respiration?
The F1 part of the ATPase is removed from the membranes; the oxidative phosphorylation cannot work.
163
What are the ways that mitochondria can become uncoupled?
Their membranes can be leaky; the addition of a chemical uncoupler
164
What are the chemical uncouplers?
Serve as one-way proton carriers what shuttle a proton across the membrane down the gradient. Include CCCP, 2,4-dinitrophenol (DNP), FCCP.
165
What is state 3 respiration?
Rapid oxygen consumption.
166
What is state 4 respiration?
When the ADP runs out and the slope drops back to a much lower level.
167
What is the appearance of the mitochondria when they are in state 3 respiration?
They have a large periplasmic space and the matrix appears condensed.
168
What is the appearance of the mitochondria when they are in state 4 respiration?
More typical with very little periplasmic space.
169
What is the uncoupler protein?
UCP1; termogenin; transports fatty acid anions across the inner membrane from the matrix in exchange for a counter ion.
170
What is the uncoupler protein activated by?
Free fatty acids that are produced by lipolysis in response to hormones.
171
What is a required cofactor of uncoupling protein?
Ubiquinone
172
What is the chemiosmotic hypothesis?
The inner membrane is impermeable to protons, which permits the controlled leak of protons down the gradient through the ATP synthase to make ATP.
173
What happened when light was applied to bacteriorhodopsin in a reconstitution experiment?
They pumped protons into the vesicles; the ATP synthase was able to make ATP.
174
What does the c subunit of the Fo subunits have in the middle of the helix?
Aspartate, which is required for the proton channel.
175
What is required for the F1 particle to be sensitive to oligomycin?
OSCP-oligomycin sensitivity conferring protein.
176
What is an antibiotic inhibitor of the ATPase?
Oligomycin
177
What is the subunit composition of F1?
Alpha 3, beta 3, gamma, delta, epsilon.
178
Which subunits of F1 are the active catalytic subunits?
The beta subunits
179
What causes distortions or conformational changes in the beta subunits of F1?
The significant differences in the gamma subunit interactions with the three catalytic beta subunits.
180
What is the model of how the ATP synthase works called?
The binding change mechanism.
181
What is the first postulate of the binding change mechanism?
That the energy of the proton gradient is not used to form ATP but to release ATP from a very tight binding site where it forms spontaneously.
182
What does the release of tightly bound ATP require?
The energy of the proton gradient converted into the mechanical energy of protein conformational changes.
183
What is the second postulate of the binding change mechanism?
That the three catalytic sites are each in a unique conformation and the conformations are interconvertible.
184
What are the three catalytic sites that represent the different stages of the catalytic cycle?
L-loose; T-tight; O-open
185
What is the third postulate of the binding change mechanism?
That conformational changes at the three sites are driven by rotation of the asymmetric gamma subunit relative to the F1 ball.
186
T/F Energy is needed to release ATP
True
187
What is the P/O ratio?
How many ATP molecules are produces per oxygen consumed.
188
How many electrons and protons does it take to reduce oxygen to water?
4
189
What is the elevator model?
It suggests that protons start their passage through the membrane in subunit a, then move onto one of the c subunits which then carries the proton as the ATPase rotor moves 1/12th or 1/10th of a full circle.
190
T/F The number of c subunits dictates efficiency.
True
191
How many ATP are produced per 4 protons?
One
192
What subunits form the rotor of the molecular motor of ATP synthase?
The c subunit ring is attached to the epsilon and gamma subunits.
193
What subunits form the stator of the stationary part of ATP synthase?
a subunit, b subunit, apha, beta and delta subunits.
194
How many ATP do we get for one glucose?
32 ATP
195
How many times per day does the ATP in your body turn over?
About 200 times.
196
What is the flux of adenine nucleotide through the ADP/ATP carrier close to every day?
Your body weight.
198
What are the two roles of cytochrome P450?
Drug metabolism and Lipid metabolism
199
Where did cytochrome P450 get its name from?
P=pigment, strong absorption band at 450nm; a reduced CO difference spectrum; proteins have a heme group.
200
What ligand is above the plane of the heme in cytochrome P450?
Thiolate anion, a sulfur with a negative charge.
