biochem lecture 9 pt 1 Flashcards

1
Q

glwhat molecules can be used to synthesize glucose via gluconeogenesis

A

pyruvate, lactate, etc.

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2
Q

gluconeogenesis

A

synthesis of glucose from non carbon precursors

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3
Q

what are glycolysis and gluconeogenesis

A

opposite pathways

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4
Q

what do both pathways have in common

A

reciprocally regulated

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5
Q

what do mammals require to sustain us

A

carbs

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6
Q

where do we get carbs

A

diet, glycogen stores (liver and muscle), gluconeogenesis

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7
Q

absorptive phase

A

immediate access of glucose from the things we eatt

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8
Q

post-absorptive phase

A

short term starvation conditions; we rely on glycogen stores to provide glucose source

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9
Q

what do we rely on for glucose in short-term starvation conditions

A

glycogen stores

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10
Q

what happens if we don’t get more glucose (no more from diet or we’ve depleted stores)

A

we begin gluconeogenesis

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11
Q

how does gluconeogenesis initiate/progress

A

initiates slowly overtime, gradually increases to sustain organ function

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12
Q

what happens when you go beyond intermediate starvation to prolonged starvation (many days)

A

we see decrease in gluconeogenesis

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13
Q

why is there decrease in gluconeogenesis after a while

A

cuz there is a lack of carbon skeletons necessary to provide glucose via gluconeogenesis

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14
Q

what do you need in order to sustain life

A

supplementation of carbs

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15
Q

main sources of glucose needed to sustain life

A

dietary/exogenous, glycogen stores, and gluconeogenesis

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16
Q

when are glucose stores depleted

A

periods of starvation, fasting beyond a day

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17
Q

gluconeogenes invovles

A

pyruvate –> glucose

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18
Q

how many pyruvates do we need to make 1 glucose

A

2 pyruvates

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19
Q

what is required

A

2 NADH, 4 ATP, 2 GTP

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20
Q

glucogenic molecule

A

any molecule that can be converted into pyruvate

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21
Q

examples of glucogenic molecules

A

lactate, AAs, glycerol

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22
Q

so what does that mean if a molecule is glucogenic

A

can derive gluocse from that precursors

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23
Q

what are glycerol again

A

backbone of neutral fats

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24
Q

what are bypass reactions

A

unique to gluconeogenesis

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25
Q

describe bypass rxns

A

diff enzymes that catalyze a step in glycolysis, deff enzymes catalyzing the reverse step

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26
Q

what are irreversible glycolytic enzymes

A

hexokinase, PFK, pyruvate kinase

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27
Q

what are enzymes of gluconeogenesis

A

pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphate, glucose-6-phosphate

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28
Q

what are irreversible steps in glycolysis

A

exergonic

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29
Q

what are these steps then in other drxn

A

exergonic

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30
Q

each of these bypass rxns enzyme catalyzes what

A

an exergonic step

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31
Q

are these steps reversible or irreversible

A

technically reversible, but its mostly unidirectional so irreversible

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32
Q

what is importance of having unique enzymes

A

is something is unidirectional, then we can’t have the same enzymes

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33
Q

in order to have each of those steps occurring in one direction, and not influenced by flux, what do you need

A

need a different enzyme

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34
Q

how are the 3 glycolytic and 4 gluconeogenic enzymes controlled

A

reciprocally controlled by same hormones insulin and glucagon

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35
Q

describe example of this reciprocal control

A

if you’re stimulating glycolysis, means that 3 enzymes that catalyze 3 exergonic steps are gonna be active, while simultaneous inactivation of gluconeogenic bypass rxn enzymes

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36
Q

what is understanding the importance of bypass rxns crucial force

A

understanding how we have reciprocal control in a seemingly reversible process (glycolysis vs. gluconeogenesis)

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37
Q

what are key points of regulation going to involve

A

these bypass reactions

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38
Q

what 4 enzymes are bypass reactions in gluconeogenesis catalyzed by

A

pyruvate carboxylase, phosphoenolpyruvate carboxylase, fructose-1,6-bisphosphatase, glucose-6-phosphotase

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39
Q

why is it 4 steps instead of 3

A

process for PEP to pyruvate conversion in glycolysis is one step BUT pyruvate to PEP is two step process (via formation of oxaloacetate)

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40
Q

what catalyzes the first step in pyruvate to PEP

A

pyruvate carboxylase

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41
Q

what catalyzes the 2nd step

A

phosphoenolpyruvate carboxylase

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42
Q

what enzyme catalyzes the bypass of pyruvate kinase

A

pyruvate carboxylase

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43
Q

what do carboyxlaes do

A

tack on carbons to structures

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44
Q

what do decarboxylases do

A

remove carbons from structure

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45
Q

what does pyruvate carboxylase do

A

addition of carbon in form of bicarbonate to pyruvate, generates oxaloacetate

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46
Q

what rxn does pyruvate carboxylase do

A

pyruvate –> oxaloacetate

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47
Q

what rxn (thermodynamically speaking) is pyruvate carboxylase catalyzing

A

exergonic or irreversible step

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48
Q

what cofactor requirement do carboxylases have

A

biotin

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49
Q

what activates carboxylase

A

acetyl CoA

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50
Q

what is acetyl CoA an indicator of

A

low E state in the cell;

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51
Q

what is acetyl CoA serving as low E indicator important for

A

important for catalyzing synthesis of glucose

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52
Q

what kinda rxn is this first bypass step

A

anaplerotic rxn

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53
Q

what is an anaplerotic rxn

A

rxns that replenish intermediates in a pathway

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54
Q

what is oxaloacetate synthesized for

A

final product in TCA: in order to keep eTCA going, we have synthesis of oxaloacetate thru this bypass rxn

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55
Q

what does the second enzyme do

A

oxaloacetate –> phosphoenolpyruvate

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56
Q

what enzyme for second one

A

phosphoenolpyruvate carboxykinase (PEPCK)

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57
Q

when does PEPCK synthesis increase

A

increases in fasting

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58
Q

where does first bypass step occur

A

pyruvate to oxaloacetate conversion is in mitochondrial matrix

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59
Q

where does second bypass step occurs

A

in cytosol

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60
Q

so what is needed in order for gluconeogenesis to occur

A

oxaloacetate needs to go thru interconversion steps involving malate formation

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61
Q

describe thermodynamics of pyruvate carboxylase

A

metabolically irreversible

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62
Q

what does pyruvate use as a cofacto

A

biotin

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63
Q

what is pyruvate carboxylase allosterically activated by

A

acetyl CoA

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64
Q

what kinda rxn is pyruvate carboxylase step

A

anaplerotic for TCA cycle

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65
Q

how is pyruvate carboxylase anaplerotic for TCA cycle

A

cuz it replenishes oxaloacetate for TCA cycle

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66
Q

where does pyruvate carboxylase step occur

A

mitochondria

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67
Q

what is biotin utilized by

A

carboxylase

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68
Q

how is biotin utilized

A

covalently associated to specific lysine residue in active site of carboxylase

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69
Q

what happens to pyruvate and where

A

pyruvate is carboxylated into oxaloacetate, by pyruvate carboxylase, in mitochondria

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70
Q

what is needed for pyruvate to enter gluconeogenic pathway

A

needs to enter mitochondrial matrix

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71
Q

how does pyruvate get into mitochondrial matrix

A

specific transporters

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72
Q

basically what is needed for pyruvate to go into TCA cycle

A

needs to get into mitochondrial matrix

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73
Q

what happens to pyruvate in mitochondria

A

converted to oxaloaecetate by pyruvate carboxylase

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74
Q

what happens to oxaloacetate in mitochondria

A

converted to malate

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75
Q

who does oxaloacetate –> malate

A

malate dehydrogenase

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76
Q

what does oxaloacetate to malate conversion allow for

A

export of carbon skeletons originally derived from pyruvate back into cytosol from mitochondrial matrix

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77
Q

sum up conversion step in first two bypass rxns

A

pyruate –> oxaloacetate (in mitochondria) –> malate (shuttled out of mitochondria) –> oxaloacetate

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78
Q

why do we need to do a bunch of conversion reactions

A

becuase there is no oxaloacetate transporter, so it can’t be shuttled out of mitochondria

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79
Q

what enzyme carries out this interconversion

A

malate dehydrogenase

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80
Q

sum up what malate dehydrogenase does

A

oxaloacetate –> malate (by malate dehydrogenase), malate shuttled out of mitochondria into cytosol, then cytosolic malate dehydrogenase which does malate –> oxaloacetate

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81
Q

what enzyme does oxaloacetate –> malate

A

malate dehydrogenase

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82
Q

what enzyme does malate –> oxaloacetate

A

cytosolic malate dehydrogenase

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83
Q

what happens once we get malate –> oxaloacetate

A

we can continue on w/ gluconeogenesis

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84
Q

what is 3rd bypass rxn

A

fructose -1,6-bisphosphate –> fructose-6-phosphate

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85
Q

what enzyme for 3rd bypass rxn

A

fructose-1,6-bisphosphatase

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86
Q

what kinda rxn (thermodynamically) is fructose-1,6-bisphosphatase

A

metabolically irreversible rxn

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87
Q

what are allosteric inhibitors of F-1,6-BPase

A

AMP, fructose-2,6-bisphosphate

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88
Q

what is the glycolytic counterpart for this 3rd bypass rxn

A

conversion of F6P into F,1-6-BP

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89
Q

what enzyme in glycolysis

A

PFK-1

90
Q

why do we require diff enzymes

A

both exergonic steps but occurring in opposite directions, so diff enzymes needed

91
Q

describe reciprocal control in gluconeogenesis and glycolysis

A

if one enzyme active other one is gonna be shut down

92
Q

what is fructose-2,6-bisphosphate important for

A

reciprocal regulation of these two enzymes

93
Q

what is final bypass step of gluconeogenesis

A

glucose-6-phosphate –> glucose

94
Q

what enzyme catalyzes final bypass step

A

glucose-6-phosphatase

95
Q

describe thermodynamics of this final bypass rxn

A

irreversible

96
Q

what kinda rxn is G6P to glucose

A

hydrolysis rxn

97
Q

where is glucose-6-phosphatase found

A

only liver and kidney

98
Q

so only which tissues can serve as as source of glucose from gluconeogenesis

A

liver and kidney

99
Q

what enzyme catalyzes the glycolytic counterpart

A

hexokinase

100
Q

what are we doing to glucose-6-phosphate to glucose

A

dephosphorylating it

101
Q

why do we phosphorylate glucose to G6P

A

traps it inside cell

102
Q

what would happen without glucose-6-phosphatase in gluconeogenesis

A

that glucose would be trapped in cell, can’t go to other parts of body; so we need to dephosphorylate it

103
Q

what is main source of glucose via gluconeogenesis

A

liver, little bit from kidney

104
Q

what is glucose-6-phosphate a precursor for

A

glycogen and glucose synthesis

105
Q

where is glucose-6-phosphatase found in

A

only liver and kidney

106
Q

where is glucose-6-phosphatase hgihly regulated

A

in liver

107
Q

what is glucose-6-phosphate a starting point for

A

pentose phosphate pathway

108
Q

is glucsoe-6-phosphatase expressed in every tissue or only limited ones

A

limited tissue expression; only liver and kidney

109
Q

where are major contributions/release of glucose into blood gonna come from

A

liver mainly

110
Q

so why is liver strictly regulating glucose-6-phosphatase enzyme

A

because major contributions/release of glucose come from the liver

111
Q

how many NTPS (so like ATP/GTP) does it take to synthesize glucose

A

6 NTPs

112
Q

how many NTPs are generated from glycolysis

A

2 nucleotide triphosphate molecules

113
Q

is gluconeogenesis favorable or unfavorable

A

unfavorable (because we are synthesizing something)

114
Q

how much extra high phosphoryl transfer potential molecules does it take to drive this unfavorable gluconeogenesis pathway

A

4 extra

115
Q

how many pyruvates required to make glucose

A

2 pyruvates

116
Q

what does gluconeogenesis require

A

some investment of ATP E

117
Q

why do we need an input of E to synthesize glucose

A

because it’s endergonic

118
Q

does that E needed to synthesize glucose only come from ATP

A

no; body needs additional E sources

119
Q

where is flux through a pathway controlled at

A

rate-limiting steps

120
Q

how can flux thru the rate determining steps be altered

A

allosteric control, covalent modifications, substrate cycles/futile cycles, genetic control (regulate transcription/translation of enzymes)

121
Q

what can you do when you have 2 directly opposing pathways

A

reciprocal control

122
Q

why can we control flow of intermediates thru these pathways at these exergonic rate limiting steps

A

because these steps are unidirectional; by limiting or depleting reactant of that step, you can limit the amount of byproduct produced in that step

123
Q

what are reciprocally regulated in the liver

A

glycolysis and gluconeogenesis

124
Q

what does this reciprocal regulation allow

A

prevents both pathways from operating at the same time

125
Q

what does high. [AMP] indicate for glycolysis and gluconeogenesis

A

low energy state; need ATP

126
Q

what does high [ATP] mean

A

high E state, intermediates are abundant

127
Q

what is another allosteric regulator of gluconeogenesis/glycolysis

A

citrate concentration

128
Q

high [citrate] means

A

high energy state, abundant intermediates

129
Q

what does insulin stimulate

A

glycolysis

130
Q

what does glucagon stimulate

A

gluconeogenesis

131
Q

what are allosteric regulators

A

AMP, ATP, citrate

132
Q

what is liver a major site for

A

major site for carb metaboism

133
Q

what does insulin promote

A

glucose uptake and storage in liver, thus glycolysis

134
Q

what does insulin do in other tissues

A

inhibits glycolysis

135
Q

what does insulin do in liver

A

stimulates glycolysis; important for generating ATP E, necessary to fuel glycogenolysis, etc.

136
Q

what does glucagon stimulate

A

gluconeogenesis

137
Q

when is glucagon activated

A

intermediate starvatino conditions

138
Q

what do the points of control for allosteric regulation primarily involve

A

bypass reactions

139
Q

what are indicators of a high E state in the celly

A

acetyl CoA, ATP, citrate

140
Q

what do high E state indicators stimulate

A

gluconeogenesis

141
Q

what are low E state indicators

A

AMP, ADP

142
Q

what do low E state indicators do

A

inhibit gluconeogenesis

143
Q

what does high AMP indicate

A

energy state is low, so we need ATP

144
Q

what does low E state do

A

stimulates glycolysis while reciprocally inhibiting gluconeogenesis

145
Q

what does a lot of ATP, TCA cycle intermediates (citrate, acetyl CoA) mean

A

high E state

146
Q

what are allosteric regulators here

A

ATP/ADP/AMP, TCA cycle intermediates (citrate/acetyl CoA)

147
Q

what does ATP and TCA cycle intermediates do

A

inhibits glycolysis and stimulate gluconeogenesis

148
Q

describe futile cycle

A

what happens if both gluconeogenesis and glycolysis were activated; gluconeogenesis: fructose-1,6-bisphosphate –>fructose-6-phosphate, and then fructose-6-phosphate –> fructose-1,6-bisphosphate in glycolysis. if both enzymes active at the same time, it would be a futile cycle

149
Q

is futile cycle actually happening

A

nope; whenever one enzyme is active, the reciprocal enzyme is inactive

150
Q

what is a big part to understanding what futile cycles are

A

understanding that they do reciprocal regulation of enzymes catalyzing the opposing step in that cycle

151
Q

consider FBP-ase 1 (gluconeogenic enzyme) and PFK-1 (glycolytic enzyme). what is an important regulator for both enzymes

A

fructose-2,6-bisphosphate

152
Q

what is fructose-2,6-bisphosphate

A

isomer of fructose-1,6-bisphosphate

153
Q

is F-2,6-BP a player in gluconeogenesis/glycolysis?

A

no; it is not serving as an intermediate in either of these 2 pathways

154
Q

what is fructose-2,6-bisphosphate form important for

A

reciprocal regulation of PFK-1 and FBPase-1

155
Q

what does fructose-2,6-bisphosphate serve as

A

allosteric regulator of these two enzymes

156
Q

what does fructose-2,6-bisphosphate do to PFK-1 and FBPase-1

A

activates PFK-1 (glycolysis) while simultaneously inhibiting FBPase-1 (gluconeogenic enzyme)

157
Q

what do high levels of F26BP favor

A

activation of PFK-1

158
Q

what does activation of PFK-1 favor

A

glycolysis

159
Q

what kind of regulation is that of PFK-1 and FBPase 1 by F-2,6-BP

A

reciprocal regulation

160
Q

what does F26BP’s regulation of PFK-1 and FBPase-1 involve

A

two more enzymes

161
Q

what are these 2 more enzymes called

A

PFK-2 and FBPase-2

162
Q

are PFK-2 and FBPase-2 the same as PFK-1 and FBPase-1

A

nope

163
Q

what does PFK-2 correspond to

A

formation of F-26-BP

164
Q

what does FBPase-2 correspond to

A

reduction in F-2,6-BP levels

165
Q

so what are these enzymes with 2 in their names involved in

A

regulation or control of level of F,2-6-BP

166
Q

what does active PFK-2 favor

A

formation of fructose-2,6-bisphosphate

167
Q

what does increase in fructose-2,6-bisphosphate do

A

activates PFK-1 while inhibiting FBPase-1

168
Q

what does activates PFK-1 while inhibiting FBPase-1 do

A

favors glycolysis

169
Q

basically what does PFK-2 being active do

A

increase in F-2,6-BP, increases PFK-1, inhibits FBPase-1, which favors glycolysis

170
Q

what does FBPase-2 do

A

dephosphorylates fructose-2,6-bisphosphate do

171
Q

what does de-phosphorylating fructose-2,6-bisphosphate do

A

lowers levels of F-2,6-BP

172
Q

what does lowering F26BP do

A

less activation of PFK-1 (so less PFK1) and less inhibition of FBPase-1 (so more FBPase-1)

173
Q

what does less PFK1 and more FBPase-1 do

A

favors gluconeogenesis and inhibits glycolysis

174
Q

basically what does active FBPase-2 do

A

decrease in F-2,6-BP, so decrease PFK-1, increasees FBPase-1, which favors gluconeogenesis

175
Q

can hormones stimulate futile cycle

A

yes

176
Q

what does glucagon do

A

stimulates gluconeogenesis

177
Q

what does glucagon in liver do

A

inhibits glycolysis

178
Q

how does glucagon work in futile cycle

A

simulates cAMP, activates PKA, phosphorylates FBPase-2 and PFK2

179
Q

what does PKA do to FBPase-2 and PFK-2

A

phosphorylates them

180
Q

what does phosphorylating FBP-ase 2 do

A

activates it

181
Q

what does phosphorylating PFK-2 do

A

inhibits it

182
Q

so describe what glucagon does in futile cycle

A

glucagon –> cAMP –> PKA –> activates FBPase2, inhibits PKA-2 –> lowers F-2,6-BP –> inhibits PFK-1 and activates FBPase-2 –> favors gluconeogenesis and inhibits glycolysis

183
Q

if glucagon is active, does that mean higher or lower levels of fructose-2,6-bisphosphate

A

lower levels of f-2,6-bp

184
Q

what does glucagon do

A

stimulates gluconeogenesis

185
Q

how does glucagon stimulate gluconeogenesis in liver

A

lby lowering F-26-BP, activates FBPase-1 and inhibits PFK-1, activating gluconeogenesis

186
Q

what does insulin do

A

favors glycolysis, inhibits gluconeogenesis

187
Q

what other enzyme is at play in futile cycle

A

PP2

188
Q

how does insulin work in futile cycle

A

insulin activates PP2

189
Q

what does PP2 do to PFK2 and FBPase-2

A

dephosphorylates them

190
Q

what does dephosphorylating of PFK-2 by PP2 do

A

activates PFK-2

191
Q

what does dephosphorylating FBPase-2 by PP2 do

A

inactivates FBPase-2

192
Q

what does PP2’s dephosphorylating activity do to F-26-BP

A

activates it

193
Q

so what does insulin do to f-26-bp

A

increases fructose-2,6-bp

194
Q

what does increasing f-26-bp do

A

activates PFK-1, inhibits FBPase-1, favors glycolysis over gluconeogenesis

195
Q

what does insulin do in futile cycle (full pathway)

A

insulin –> PP2 –> inactivates FBPase2, activates PKA-2 –> increases F-2,6-BP –> increases PFK-1 and decreases FBPase-2 –> favors glycolysis and inhibits gluconeogenesis

196
Q

what does cori cycle involve

A

interconversion of waste products, their recycling to synthesize more glucose in liver via gluconeogenesis

197
Q

what was one of the issues with gluconeogenesis

A

we don’t have enough NTP equivalence from glycolysis to fuel gluconeogenesis

198
Q

what would we end up with if we just relied on glycolysis to fuel gluconeogenesis

A

energy deficiency

199
Q

corci cycle

A

describes interconnectedness b/w glycolysis and gluconeogenesis, specificaly where ATP needed to drive gluconeogenesis comes from

200
Q

where does ATP oxidation needed to drive gluconeogenesis come fom

A

beta oxidation of fats in liver

201
Q

overall what happens in cori cycle

A

pyruvate (lactic acid) generated thru fermentation accumulates in muscle, travels to liver, converted back to pyruvate, and goes thru gluconeogenesis to synthesize glucose

202
Q

what can happen in intermediate starvation conditions

A

that glucose can be used in glycolysis, like in muscle, brain, etc.

203
Q

what is gluconeogenic pathway coupled to

A

some ATP generated via oxidation of fatty acids

204
Q

what is cori cycle important for understanding

A

important in understanding linkage and thus how gluconeogenesis and glycolysis are regulated

205
Q

what happens as a result of liver being a major organ for intermediary metabolism

A

a lot of blood flow into and out of liver

206
Q

how are energy rich molecules and nutrients available from diet made available

A

partial digestion in stomach and upper parts of intestines

207
Q

where do those energy rich molecules go

A

transported to liver

208
Q

how are E rich molecules transported to liver

A

via blood flow via hepatic portal system

209
Q

how are those products from liver distributed to various parts of body

A

byproducts of the various metabolic processes that occur from liver leads to its distribution

210
Q

what does massive amount of bloodflow into and out of liver allow

A

means you can distribute intermediates of carb metabolism AND fatty acid metabolism, protein metabloism

211
Q

what is liver a big time player in

A

distribution of various types of dietary fuels, receiving waste products and intermediates that can be used in recycling pathways (like in cori cycle)

212
Q

what is cori cycle interaction b/w

A

interaction of glycolysis and gluconeogenesis

213
Q

describe cori cycle step 1

A

lactate from peripheral tissues goes to liver and made to glucose (lactate –> glucose in liver)

214
Q

cori cycle step 2

A

glucose goes back to peripheral tissues (like muscle)

215
Q

cori cycle step 3

A

uses lipid for energy

216
Q

talk about placement of liver in circulation

A

first pass at removing nutrients absorbed from intestine, makes nutrients available to other tissues

217
Q

what does liver participate in

A

interconversion of all types of metabolic fuels (carbs, AAs, fatty acids)

218
Q

what does liver regulate

A

distribution of dietary fuels, supplies fuel from its own reserves

219
Q

where does liver supply fuel

A

from its own reserves

220
Q

what does cori cycle do

A

generates ATP

221
Q

how does cori cycle make ATP

A

(lactate –> glucose –> lactate) thru this interconversion