Test 3 Review Flashcards

(230 cards)

1
Q

TWO enzymes _______, _________ are needed in Gluconeogenesis to bypass the highly irreversible step catalyzed by Pyruvate kinase in Glycolysis.

A

Pyruvate carboxylase and PEP carboxykinase

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2
Q

Decarboxylation of oxaloacetate is energetically favorable and can help drive?

A

PEP formation.

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3
Q

______ is used as the phosphoryl group donor which is catalyzed by PEP carboxykinase

A

GTP

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4
Q

PC is a mitochondrial enzyme that is allosterically activated by______.

A

Acetyl CoA

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5
Q

Accumulation of Acetyl CoA from fatty acid oxidation (during fasting/starvation) signals the liver to direct ?

A

Pyruvate to Oxaloacetate for Gluconeogenesis.

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6
Q

_____ _________ uses biotin as a cofactor to “carry” CO2 in the form of carboxybiotinyl group.

A

Pyruvate Carboxylase

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7
Q

________ __ ___ _________ is the third reaction unique to Gluconeogenesis and is metabolically irreversible

A

Fructose 1,6-bisphosphatase

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8
Q

F1,6BPase is allosterically inhibited by ______ and _________ ___ ___ ____________(F2,6BP). PFK1 and F1,6BPase will NOT be active at the same time (reciprocal regulation in the liver).

A

F1,6BPase is allosterically inhibited by AMP and Fructose 2,6-bisphosphate (F2,6BP). PFK1 and F1,6BPase will NOT be active at the same time (reciprocal regulation in the liver).

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9
Q

_________ _________, the LAST of the gluconeogenesis reactions, produces FREE Glucose, which is released from hepatocytes into the blood stream

A

Glucose 6-phosphatase

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10
Q

G6Pase is localized to the __________ ___________ and is most strongly expressed in LIVER. It may transport the G6P into the ER where the active site can then hydrolyze the phosphate.

A

G6Pase is localized to the endoplasmic reticulum (ER) membrane and is most strongly expressed in LIVER. It may transport the G6P into the ER where the active site can then hydrolyze the phosphate.

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11
Q
Which of the following enzymes occurs in both glycolysis and gluconeogenesis?
3-Phosphoglycerate kinase. 
Hexokinase. 
Glucose 6-phosphatase. 
Phosphofructokinase-1. 
Pyruvate kinase.
A

3-Phosphoglycerate kinase.

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12
Q
Under what metabolic conditions does gluconeogenesis typically occur?
Starvation
Fasting
Intense exercise
A and B
All of the above
A

A and B

All of the above

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13
Q

Pyruvate Dehydrogenase (PDH) is a multienzyme complex. What advantages do complexes like PDH have?

A

Increased rate of movement between enzyme active sites (close proximity).
Substrate channeling to reduce intermediate side reactions.
Opportunities for coordinate control of all reactions carried out by the complex.

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14
Q

3 enzymes make up the whole PDH complex What are they?

A
E2 = Dihydrolipoamide acetyltransferase (60 subunits)
E1 = Pyruvate dehydrogenase (60 subunits)
E3 = Dihydrolipoamide dehydrogenase (12 subunits)
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15
Q

The First Cofactor, _________ decarboxylates Pyruvate, the First Substrate, and forms the acetaldehyde adduct of TPP, HETPP.

A

Thiamine PP (TPP)

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16
Q

STEP 2 uses a Second Cofactor, _____________, as an oxidizing agent to convert the Acetaldehyde-TPP adduct to the oxidized Acetyl-dihydrolipoamide form.

A

LIPOAMIDE (a prosthetic group),

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17
Q

_________ is the Third Cofactor involved in the Pyruvate Dehydrogenase Complex, and is also the Second Substrate

A

Coenzyme A

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18
Q

STEP 4: A _________ of E3 Oxidizes the Reduced Lipoamide of E2

A

STEP 4: A disulfide group of E3 Oxidizes the Reduced Lipoamide of E2

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19
Q

_____ is the Fourth Cofactor involved in the PDH complex. This prosthetic group serves as the oxidant to convert reduced _____ back to the active oxidized _______ form.

A

FAD is the Fourth Cofactor involved in the PDH complex. This prosthetic group serves as the oxidant to convert reduced Dithiols back to the active oxidized disulfide form.

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20
Q
Gluconeogenesis must use “bypass reactions” to circumvent three reactions in the glycolytic pathway that are highly exergonic and essentially irreversible.  Reactions carried out by which three of the enzymes listed must be bypassed in the gluconeogenic pathway?
Hexokinase
Phosphoglycerate kinase
Phosphofructokinase-1
Pyruvate kinase
Triosephosphate isomerase
A

Hexokinase
Phosphofructokinase-1
Pyruvate kinase

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21
Q

Which of the following statements about gluconeogenesis in animal cells is true?
A) A rise in the cellular level of fructose-2,6-bisphosphate stimulates the rate of gluconeogenesis.
B) The conversion of fructose 1,6-bisphosphate to fructose 6-phosphate is not catalyzed by phosphofructokinase-1, the enzyme involved in glycolysis.
C) The conversion of glucose 6-phosphate to glucose is catalyzed by hexokinase, the same enzyme involved in glycolysis.
D) The conversion of phosphoenolpyruvate to 2-phosphoglycerate occurs in two steps, including a carboxylation.

A

The conversion of fructose 1,6-bisphosphate to fructose 6-phosphate is not catalyzed by phosphofructokinase-1, the enzyme involved in glycolysis.
`

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22
Q

Which of the following coenzymes is required by E1 of the pyruvate dehydrogenase complex for catalytic activity?

thiamine pyrophosphate
lipoic acid
FAD
NAD+
biotin
A

thiamine pyrophosphate

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23
Q

Which of the following serves as a “swinging arm” in Pyruvate Dehydrogenase when it transfers a reaction intermediate from one active site to the next?

A

Lipoamide

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24
Q

How many electrons can be carried by the prosthetic group in cytochrome c ?

A

1

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25
Cytochrome c oxidase forms a transient radical at a _____ side chain adjacent to the heme a3-ligated O2
tyrosine
26
Which complex is unable to directly contribute free energy to power ATP synthesis?
Complex 2
27
The functional core of Complex III includes: -cytochrome c1, iron-sulfur protein (Rieske). -cytochrome c1, cytochrome b, myoglobin. -cytochrome c1, cytochrome b, iron-sulfur protein (Rieske). all of the above none of the above
cytochrome c1, cytochrome b, iron-sulfur protein (Rieske).
28
How many ATP molecules are synthesized from the oxidation of 1 NADH molecule?
2.5
29
What is gluconeogenesis, when does it occur?
Occurs when dietary glucose is not available and liver used glycogen stores. Glucose is then synthesized from non-carbohydrate pre-cursors
30
Non-carbohydrate precursors are?
lactate, pyruvate, citric acid intermediates, and AA residues
31
Before non-carbohydrate precursors can enter into gluconeogenesis what must they be converted into?
oxaloacetate
32
What is the enzyme that converts pyruvate to oxaloacetate?
pyruvate carboxylase
33
What is the enzyme that converts oxaloacetate into Phosphoenolpyruvate?
PEPCK
34
What organic compound does pyruvate carboxylase use to catalyze ATP driven fromation of axaloacetate from pyruvate?
Botin
35
What occurs when PEPCK converts oxaloacetate to phosphoenolpyruvate?
a rxn occurs that uses GTP as a phosphoryl-group donor
36
Both __________ and ________ occur in the mitochondria but where do enzymes that convert PEP to glucose occur?
Pyruvate Carboxylase and PEPCK cytosolic
37
For human gluconeogenesis to occur what must happen since conversion to oxaloacetate occurs in mitochondria and the rest of gluconeogenesis occurs in the cytosol?
Oxaloacetate must either leave mitochondria or PEP mitochondria to cytosol
38
Fructose-1-6-bisphosphate is converted to Fructose-6-phosphate by what enzyme in gluconeogenesis?
Fructose Bisphosphotase
39
What enzyme converts Fructose-6-phosphate to Glucose-6-phosphate
Glucose-6-phosphatase
40
For cytosolic PEPCK, what must oxaloacetate be converted into?
Aspartate or Malate where the mitochondrial transport systems exsist
41
The most common transport system is called the __________ _______ route
Malate Dehydrogenase route
42
What is the Malate Dehydrogenase route?
Results in transport of Reducing Equivalents from mitochondria to cytosol and uses mitochondrial NADH and produces cytosolic NADH
43
The Aspartate Aminotrasnferase route does not use what?
NADH and because it does not produce cytosolic NADH it is not commonly used with the exception of when lactate is the pre-cursor used
44
Glycolytic Rxns catalyzed by Phosphofructokinase and hexokinase are _________ in gluceoneogenesis direction and therefore?
endergonic and therefor must be bypassed by gluceneogenic enzymes
45
Fructose-6-phosphate becomes glucose-6-phosphate in gluconeogenesis via?
isomerization
46
What is the cost of the bypass of glycolytic enzymes?
Net loss is 4 ATP due to Glycolsis netting 2 ATP but conversion from pyruvate back to glucose costs 6 ATP
47
What is Fructose-2-6-Bisphosphate?
Activates Phosphofructokinase Inhibits Fructose-1-6-Bisphosphate (Allosteric Activator)
48
What determines the concentration of Fructose-2-6-Bisphosphate in the cell?
Depends on balance between it's rate of synthesis and degradation by phosphfructokinase and fructose bisphosphate 2
49
Fructose-2-6-Bisphosphate is a __________ enzyme that is regulated by a variety of allosteric inhibitors and by phosphorylation and dephosphorylation as catalyzed by PKA and Phosphoprotein kinase
bi-functional
50
Balance between gluconeogenesis and glycolsis is under what type of control?
hormonal control
51
A drop in blood glucose would result in what pathway being favored? (gluceoneogenesis or glycolsis)
gluceoneogenesis
52
A raising of blood glucose would result in? | gluceoneogenesis or glycolsis
promotion of glycolsis
53
The liver, depending on levels of blood glucose will convert _________ to _________ using Liver PFK-2. Vice versa the liver converts __________ to __________ using FBPase2
The liver, depending on levels of blood glucose will convert fructose-6-phosphate to fructose-2-6-phosphate using Liver PFK-2. Vice versa the liver converts fructose-2-6-phosphate to fructose-6-phosphate using FBPase2
54
What allosteric effect does Acetyl-CoA have?
activates pyruvate carboxylase
55
Pyruvate kinase is allosterically inhibited by?
Alanine in liver
56
What is the Net equation of Gluconeogenesis?
2 Pyruvate + 2 NADH + 4 ATP+ 2GTP+6H20+2H ---> Glucose +2NAD+2GTP+6Pi
57
Where do all reactions of the TCA cycle occur?
in the mitochondria of eukaryotic cells
58
What is step 1 of the TCA cycle?
the conversion of pyruvate to Acetyl-CoA
59
What enzyme complex is used for the conversion of pyruvate to Acetyl-CoA?
Pyruvate dehydrogenase
60
What are the 3 enzymes that make up the Pyruvate dehydrogenase complex?
E2: Dihydrolipoamide acetyl transferase E1: Pyruvate Dehydrogenase E3: Dihydrolipoamide dehydrogenase
61
The Coenzymes associated with E2 are?
Lipoic Acid and coenzyme A
62
What does Lipoic Acid do within the E2 complex?
convalently linked to a lys res. | accepts hydrozy ethyl carboanion from TPP as acteyl group
63
What does Coenzyme A do within the E2 complex?
Acts as a substrate | Accepts a acteyl group from lipoamide
64
The Coenzymes associated with E1 are?
Thiamine Pyrophosphate
65
What does Thiamine Pyrophosphate do within the E1 complex?
Decarboxylates pyruvate yeilding a hydroxyethyl TPP carbanion
66
The Coenzymes associated with E3 are?
Flavin Adenine Dinucleotide | Nicotinamide Adenine Dinucleotide
67
Flavin Adenine Dinucleotide does what within the E3 complex?
is reduced by lipoamide
68
Nicotinamide Adenine Dinucleotide does what within the E3 complex?
substrate for E3 | is reduced by FADH2
69
What are the regulatory steps in the TCA Cycle?
1) Pyruvate De-hydrogenase 2) Citrate synthase 3) )Isocitrate De-hydrogenase 4) )Alpha ketogluarate dehydrogenase
70
pyruvate dehydrogenase converts?
pyruvate to acetyl-coa
71
Citrate synthase converts?
Acetyl-CoA to citrate
72
Isocitrate De-hydrogenase converts?
Isocitrate to alpha-ketoglutarate
73
Alpha ketogluarate dehydrogenase converts?
Alpha ketogluarate to succinyl-coA
74
The enzymes in the TCA cycle that are reversable are?
1) Aconitase 2) Succinyl-CoA synthase 3) Succinate De-hydrogenase 4) Fumarase 5) Malate dehydrogenase
75
Which steps in the TCA cycle produce NADH?
1-pyruvate dehydrogenase 2-Isocitrate De-hydrogenase 3-Alpha ketogluarate dehydrogenase 4-Malate Dehydrogenase
76
What steps in the TCA cycle produce FADH2?
Succinate Dehydrogenase
77
What steps in the TCA cycle produce GTP?
Succinyl-CoA synthase
78
What are the allosteric inhibtors of the TCA cycle?
NADH and ATP
79
What are the steps of citrate synthesis?
1-Asp375 deprotonates acetyl-coA at methyl group generating an enol -which is stablized by H-bonding to His274 2-Acetyl-CoA enolate attacks oxaloacetate while His 320 donates a proton to oxaloacetate carbonyl. Forms citryl-coA 3-Citryl-CoA is hydrolzed to a citrate and coA
80
What are the steps of Aconitase?
1-Removes H2O from citrate to form c-c bond of cis-aconitate 2-Rearranges by re-addition of H2O to form 2R, 3S-isocitrate
81
What are the Steps of Isocitrate De-hydrogenase?
1-Two H atoms removed from the 2ndary OH of Isocitrate forming alpha-keto group THIS FORMS NADH
82
What are the Steps of the PDH Complex?
1-E1: 1st cofactor TPP decarboxylates pyruvate forming acetylaldehyde adduct HETPP 2-2nd cofactor Lipoamide acts as oxidizing agent to convert HETPP to oxidized Acetlyl-Dihydrolipoamide form 3-E3: Transfers the Acetyl Group from dihydrolipoamide adducts to hs-coA forming acetyl coA 4-Disulfide group of E3 oxidzes the reduced lipoamide of E2 5-FAD group of E3 oxidizes the reduced dithols of E2 forming FADH2
83
Step 1 of PDH Complex- CoFactor: What's formed:
Step 1 of PDH Complex- CoFactor: TPP What's formed: HETPP
84
Step 2 of PDH Complex- CoFactor: What's formed:
Step 2 of PDH Complex- CoFactor: Lipoamide What's formed: Acetyl-dihydrolipoamide
85
Step 3 of PDH Complex- CoFactor: What's formed:
Step 3 of PDH Complex- CoFactor: Coenzyme A What's formed: Acetyl-CoA
86
Step 4 of PDH Complex- CoFactor: What's formed:
Step 4 of PDH Complex- CoFactor: None What's formed: Lipoamide reactivated
87
Step 5 of PDH Complex- CoFactor: What's formed:
Step 5 of PDH Complex- CoFactor: FAD What's formed:FADH2
88
What are the steps of alpha-ketoglutarate de-hydrogenase complex?
with an input of coAsh and output of NADH alpha-ketoglutarate is converted into succinyl-coA
89
What are the steps of Succinyl-CoA synthetase?
1-succinyl-coA reacts with free phosphate to form succinyl-phosphate and CoA 2-FAD group transfers electrons through iron sulfur clusters to Q forming QH2 3-This forms succinate
90
What are the steps of Succinate dehydrogenase complex?
Substrates adjacent CH2 groups undergo two 2H removal and yeild trans double bond resulting in FADH2 + Fumarate
91
What are the Steps of Fumerase?
Stereospecific addition of H2O to the trans double bond of Fumerate to L-malate
92
What are the steps of Malate De-hydrogenase?
NAD+ is used to oxidize 2ndary OH of Malate to a ketone producing NADH and forming oxaloacetate
93
In the malate dehydrogenase reaction, where does equilibrium lie and what does these mean?
Equilibrium leans towards malate, which means oxaloacetate is limiting substrate of TCA cycle
94
Energy in the TCA cycle is conserved through what reduced coenzymes>
3 NADH, 1 FADH2 and 1 GTP | NADH and FADH2 will be reoxidized in ETC
95
The total ATP yield from glycolsis to the TCA cycle is ____ total ATP
32
96
The TCA cycle itself produces how many ATP through what reduced coenzymes
6 NADH->15 ATP 2FADH->3 ATP 2 GTP->2 ATP
97
The pyrvate dehydrgenase complex controls supply of what?
Acetyl CoA | this makes it a key regulatory point
98
What is PDH complex controlled by?
Product inhibition by NADH and Aceytl-CoA | Covalent modification of E- (phosphorolation)
99
What hormone activates PDH?
insulin
100
What molecules turn off PDH?
NADH and Acetyl-CoA
101
Where do the final stages of aerobic oxidation of biomolecules occur?
in the mitochondria
102
Reduced co-enzymes from the TCA cycle enter?
the electron transport chain to be oxidized to produce a proton gradient to drive ATP synthesis
103
NADH and NAD+ enter the mitochondria for ETC how?
They have no carrier so they instead have two systems called: Glycerol Phosphate Shuttle Malate Aspartate Shuttle
104
Transport of ATP, ADP, and Pi across the membrane is performed by>
Adeneine Nucleotide Translocase Antiport mechanism for ATP/ADP Symport mechanism for Pi and H+
105
Electrons flow through ETC components in a direction towards?
More positive reduction potiential (E) values | Electrons flow from NADH to O2
106
What mobile coenzymes serve as electron carriers between ETC complexes?
Ubiquinone and Cytochrome c
107
How do electrons enter the ETC?
``` 2 at a time via NADH or oxidation of succinate Flavin coenzymes (FMN or FAD) Fe ions can accept/donate 1 e- at a time ```
108
What are the cytochromes?
Heme proteins where Fe(II)/Fe(III) are used for e- transfer
109
How do cytochromes get there names?
Each of the different groups of cytochromes contain different forms of heme A, B, C and these are how they get there names
110
What is Ubiquinone?
A lipid soluble molecule that diffuses with lipid bilayer and accepts electrons from complexes 1 and 2 passing them to 3
111
What are the inhibitors of complex one?
Rotenone or Amytal
112
What does complex 1 do?
Containing both NADH and Ubiquinone oxidoreductase it transfers electrons from NADH ultimately to Q and transfers E- ashydride ion to FMN FMN transfers Electrons through complex one to Q
113
What does complex 2 do?
Accepts electrons from succinate and catalyzes the reaction of Q to QH2 (this reaction consumes protons but no net loss occurs) FAD here is reduced by 2 e-trans. of hydride ion from succinate, releasing 2H into matrix.
114
What is the inhibitor of complex 3?
Antimycin A
115
What does complex 3 do?
Transfers e- from ubiquonol (Q) to cytochrome c | The oxidation of one QH2 is accompanied by the translocation of 4 H+ across the membrane to intermembrane space
116
Complex 3 has a special feature involving Coenzyme Q-What is this feature?
It has two binding cites for Co-enzyme Q Qo-binds near ISP and close to heme bl Q1- binds both Q and the semiquinone Anion Q- near heme bh close to matrix
117
Sum up the Q cycle:
- Q is reduced to QH2 in a two step reaction involving a fixed semiquinone intermediate. 2nd electron is transfered to semiquinone to mobile QH2 - For every pair of electrons that pass through complex 3 to cytochrome c, 4 protons are translocated across the membrane (these are released from QH2) - 2 molecules of cytochrome c are reduced and these mobile carriers transport e- to complex IV
118
Complex IV contains what powerful oxidizer?
cytochrom c oxidase
119
What does complex IV do?
Catalyzes 4-electron reduction of molecular O2 to 2 H2O
120
Where does complex IV receive it's electrons?
Cytochrome c which links III and IV
121
What are the 4 redox factos in complex IV?
Cytochrome A Cytochrome A3 Single Cub ion Pair of copper ions Cua
122
How are the redox factors in complex IV organized?
Cua is in the center (2 ions) which is bridged by sulfer of 2 cys Site of intial transfer from cytochrome c
123
What are the postulates of the Chemosmotic theory?
1) Intact inner mitochondrial membrane is required for proton gradient 2) Electron transport through ETC generates a proton gradient (It pumps H+ from the matrix into the intermembrane space) 3) Return of protons into the matric via the inner membrane spanning the enzyme, ATP synthase, catalyzes phosphorylation of ADP
124
Oxidation of substrated is _________ to the phosphorylation of ADP.
coupled
125
Coupling: | Respiration (Consumtion of O2) only proceeds when?
ADP is present
126
Coupling: | The amount of O2 consumed depends on?
The amount of ADP that is added
127
Digestion of triacylglycerols is aided by the cholesterol derivatives collectively known as - bile acids (bile salts) - isoprenes. - lanosterols - statins - squalenes
bile acids (bile salts)
128
Which of the following accurately ranks lipoproteins from highest to lowest density? - Chylomicrons > HDL > LDL > IDL > VLDL - HDL > IDL > LDL > VLDL > Chylomicrons - HDL > LDL > IDL > VLDL > Chylomicrons - Chylomicrons > VLDL > IDL > LDL > HDL - VLDL > IDL > LDL > HDL > chylomicrons
HDL > LDL > IDL > VLDL > Chylomicrons
129
Uncouplers are considered __________ and why?
pronatophores because they disapate the proton gradient developed during respiration
130
What do uncouplers specifically do?
Transport H+ across the inner mitochondrial membrane | This accelerates oxidation of substrates because no phosphorylation of ADP to ATP
131
What type of molecule are uncouplers?
typically lipid soluble, weak, organic acids
132
What is protonmotive force?
energy derived from proton concentration gradient
133
How does the proton gradient provide energy?
Protons translocate into intermembrane space by electrons trans flow into membrane via ATP synthase H+ forms a proton circuit that drives ATP synthesis
134
Complex V involves what enzyme?
ATP synthase
135
FoF1 ATP synthase (complex V) uses flow of?
protons to drive synthesis of ATP
136
For each ATP synthesized by ATP synthase, how many electrons flow out>
3H+ per ATP
137
What does the F1 matrix of ATP synthase contain?
Catalytic subunits that condense Pi with ADP to form ATP
138
What does Fo of ATP synthase contain?
Proton channels that span the membrane and directs proton flow through the "turbine"
139
Passage of protons from the intermembrane space of ATP synthase through Fo does what?
Drives ATP synthesis from ADP and Pi
140
Where is the F1 subunit on ATP synthase?
Inner face of membrane in contact with matrix
141
Where is the Fo subunit on ATP synthase?
On inner membrane bilayer. C subunits form cylindrical membrane bound base which forms rotor of protein driven turbine
142
The alpha3 beta 3 oligimer of F1 (ATP SYNTHASE) is connected to?
the c unit by multisubunit "camshaft"
143
Each protomer of F1 can assume how many positions?
1 of 3 possible confirmations
144
What are the three conformations that F1 can assume?
Open Conformation Loose Conformation Tight Conformation
145
What are the steps of the confomations when ADP and Pi bind?
1-ADP and Pi bind to L 2-Inward passage of protons causes rotation, L closes to T, O opens to L, T opens to O 3-ATP synthesized from ADP and Pi in T confirmation is released as F1 sights convert to O conformation
146
What causes the rotation of C base turbine in ATP synthase?
Flow of H+ from inner membrane into matrix
147
Each c subunit of the ATP Synthase is made of how many helieces?
2 helieces
148
The conformation of of the c subunit occurs upon protonation of?
Asp61
149
The ATP synthase mechanism uses ____ H+ per turn that synthesizes ___ ATP
10 H+ per turn | 3 ATP
150
What is the P/O ratio per: NADH FADH
NADH=2.5 | FADH=1.5
151
The regulation of oxidative phosphorylation depends on?
substrate availability and cell energy demand
152
What are the important substrates in the regulation of Oxidative phosphorylation?
NADH, O2 and ATP
153
ATP/ADP in what control mechanism in oxidative phosphorylation?
2ndary
154
A high ratio of ____/_____ inhibits oxidative phosphorylation by ____ binding to reg. subunits in complex IV
A high ratio of ATP/ADP inhibits oxidative phosphorylation by ATP binding to reg. subunits in complex IV
155
__________ and ________ are the two major forms of stored energy.
Triglycerol and Glycogen are the two major forms of stored energy
156
Why are triaglycerols (TG) are very efficent energy stoes because:
TG are stored in anhydrous form | Fatty acids are more chemically reduced than AA or monosaccrides
157
Even though TG are efficent energy stores, they are _________ and due to this may be difficult to transport.
insoluble
158
Since TG are insoluble, they need what to facilitate absorption?
They need to be emulsified then digested
159
What emulsifies TG?
Bile salts and Lipases
160
What are the most abundant bile salts?
Taurocholate and Glycocholate
161
Bile salts are considered _________ because they are both hydrophilic and hydrophobic.
Amphipathic
162
How do bile salts work?
They emulsify lipids to make them more soluble and make them better subtrates for lipases
163
Bile salt ______ are critical for lipid absorption in intestinal mucousa.
micelles
164
What do pancreatic lipases?
They work with colipase to cleave TG into smaller pieces. | Results in free fatty acids and 2 monoglycerol
165
__________ containing emulsified Fatty acids and 2 monoglycerols with bile salts carry lipids close to cell membrabe of intestinal cells to facilitate absorption
Micelles
166
How many bile salts are lost (not reabsorbed in ileum)
10% are lost, but cholesterol is modified by liver to make more
167
Fatty acids within cells must be "chaperoned" by what protein?
Intestinal Fatty Acid binding protein I-FABP
168
How does I-FABP bind to Fatty acid?
Uses arg and gln with 2 water mol to coordinate carboxyl group on fatty acid
169
After Fatty acids are transported, what are they made into for distrubtion?
Lipoproteins
170
What are chloromicrons?
Lipoproteins specifically synthesized in intestinal cells to traffic dietary lipids
171
During absorption, cholesterol combines with acetyl coA in intestinal cells to form esters that?
are absorbed by chloromicrons
172
What are apoprotiens?
They give structure to lipoproteins and help direct lipoprotein metabolism
173
Chloromicrons transition from ________ to _______ for delivery to muscle for energy and adipocytes for storage.
intestine to blood
174
How is chloromicron triaglycerols cleared from blood?
Lipoprotein lipase which is a capillary enzyme
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How is lipoprotein lipase activated?
By APO-C-II
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APO-C-II is a small protein that in present in ______ and is _________ (meaning only acts in blood).
chloromicrons and extracellular
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What are the products of lipoprotein lipase?
3 free fatty acids and free glycerol
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VLDL is?
Very low density lipoprotein
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How is the TG removed from VLDL
by lipoprotein lipase
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What is LDL
A lipoprotein that is enritched with cholesterol and cholesterol esters that acts as a delivery system
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How do cells interact with LDL?
they have their own LDL receptor on their surface for when LDL is needed. Then it brings LDL in which shuts of cholesterol biosynthesis and turns on enzyme ACAT that esterfies it for storage
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HDL is used for?
used to transport excess cholesterol from tissues and brings it back to liver
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What is Atherosclerosis?
Accumulation of LDL leading to deposition of LDL in blood vessels Leads to inflammatory response Thickens vessel wall leads to plague formation
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What is familial hypercholesterol?
Mutation in LDL receptor that leads to a increase of LDL in blood
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What is Tangier diesase?
Mutation of ABCAI transporter
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What is the ABCAI transporter and how does it impact Tangier disease
Required to efflux cholesterol out of cells to HDL Mutation of this causes macrophages to be engourged with LDL and Blood vessels due to inflammation
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Where are Triaglycerols stored?
in adipocytes
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What is hormone sensitive lipase?
hydrolyzes stored TG to 3 FFA and 1 glycerol | stimulated by glucacon adn epinephrine
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What carries free fatty acids in the blood?
Serum Albumin
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Where does Beta oxidation occur?
in mitochondrial matrix
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How many FA does Beta oxidation degrade at a time?
2 carbons at a time
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What are the three stages of beta oxidation?
Activation of FA in the cytosol Transport into mitochondrial matrix Oxidation to Acetyl-CoA (-2 C units)
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What occurs during the activation stage of beta oxidation?
- FA in cytosol is activated by conversion to CoA thioesters by Acyl-CoA synthetase - ATP hydrolysis drives reaction and forms AMP and Pi - Hydroylsis of relased PPi by phyrophosphatases to 2 Pi pulls reaction forward
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What occurs during the transport stage of beta oxidation?
- Carnitine shuttle system transfers long chain fatty acetyl-coA from cytosol into mitochondrial matrix - Fatty Acetyl-CoA then is converted to Acylcarnitine - Mitochondrial beta oxidation enzymes then degrade Fatty acetyl CoA
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What occurs during the oxidation stage of beta oxidation?
-in 1 round 4 steps produce acetyl-coA and shorten fatty acetyl-coA chain by 2 carbons
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What molecules does each round of the oxidation stage of beta oxidation produce?
``` 1 mol of: QH2 NADH Acetyl-CoA Fatty Acetyl-CoA ```
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What enzyme does stage 3 step 1 of beta oxidation use?
Acyl-CoA dehydrogenase
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Acyl-CoA dehydrogenase comes in 3 sets. What are they?
long chain mid-chain short chain
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What does Acyl-CoA dehydrogenase do?
Transfer e- from FAD to 2nd FAD on ETF then reduces Q with help of Ubiqinone oxireductase
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What is the net of Acyl-CoA dehydrogenase?
QH2 and trans double bond Acyl-coA
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Steps 2-4 of stage 3 of Beta oxidation is carried out by a trifunctional enzyme. What are the individual enzymes for each step?
Step 2-ECH (2-enol-coA-hydratase) Step 3-HACD (L-3-hydroxylacyl-coA) Step 4-KACT (3-ketoacyl-coa Thiolase)
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Step 4 of stage 3 carried out by KACT does what?
- enzyme from cys adds to beta keto group of acyl-coA - Carbon/Carbon bond cleavage via claisen ester produced acyl-coA intermediate - Another residue donates H+ which causes carbanion releases acyl-coA - Free CoA attacks acyl-group off thiol which generates new acyl-coa(-2C)
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Palmitoyl CoA requires 7 cycles of beta oxidation but yeilds how much ATP?
10 ATP
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The beta oxidation cleavage product of odd chain Fatty acids is?
Propinyl-coA
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What are the enzymes required to convert Propinyl-CoA to succinul-CoA
Propionyl-coA carboxylase Methylmalonyl-CoA racemase Methylmalonyl-CoA mutase
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Methylmalonyl-CoA mutase uses a cofactor that is derived from?
Vitamin B12 and has a corrine ring with 4 pyrole nitrogens bound to Co3+ ion
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What is special about Methylmalonyl-CoA mutase's B12 derived cofacter?
it carries out carbon skeleton rearrangement
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After Propionyl-coA is converted to succinyl-coA, it enters the TCA staying for what steps?
it stays for steps 5-7 until conversion to malate which upon that time exits into the cytosol where it undergoes oxidative phosphorylation to pyruvate
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Beta oxidation of Unsaturated Fatty Acids involves?
2 extra enzymes: Enol-CoA isomerase 2-4-Dienol-CoA Reductase
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During starvation or fasting, the liver converts acetyl-coA to what?
keton bodies
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What is ketoacidosis?
When the blood becomes to acidic because there are too many ketones in blood
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What are the two most common ketone bodies?
Beta-Hydroxybutyrate Acetoacetate Acetone is lease common
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Acetoacetate is unstable and can undergo decarboxylation by beta-elimination of CO2 to form what? And what happens to that produce?
Acetone which is then excreted by the body
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Beta-hydroxybutyrate is the primary form of circulating ketone bodies. Why?
Because it is the reduced form of acetoacetate and can be used for fuel by almost all cells
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Ketone body formation occurs why?
Because the TCA cycle is not operating due to lack of oxaloacetate
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Why does equilibrium favor Beta-hydroxybutyrate?
because the level of NADH>NAD
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The liver cannot use ketone bodies because?
it lacks Ketoacyl-CoA transferase
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In type one diabetes we normally see an increase in ?
Ketone bodies
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Transport of Acetyl-CoA to the Cytosol from the Mitochondria is?
exported in the form of Citrate via the Citrate Transport System to the cytosol.
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For Acetyl-Coa to be transported into the mitochondira it must first be converted into?
Malonyl CoA | -this is a committed step
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What enzyme converts Acetyl-CoA to Malonyl CoA?
Acetyl-CoA carboxylase
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Acetyl-CoA carboxylase is inhibited by?
Fatty Acyl CoA also glucagon and Epinephrrine
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What are the 4 separate stages of Fatty Acid Synthesis
- Condensation of the precursors - Reduction of a keto intermediate - Dehydration of a secondary alcohol - Reduction of a trans double bond
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______ ____from catabolism of carbohydrates and amino acids provides the building blocks for fatty acid (FA) synthesis
Acetyl-CoA
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Successive rounds of FA Synthesis continue until a C16 ________ group is formed.
palmitoyl
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NADPH is used for building things in
Fatty Acid synthesis
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Two molecules of ATP are needed at _________ _________ and ________ _________ for fatty acid synthesis
pyruvate carboxylase and citrate lypase
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Due to the energy intensive process of FA biosynthesis, this is only done in the
fed state
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What is the main building block of FA synthesis
Malonyl CoA
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Fatty acid synthesis occurs in the?
cytosol