Gluconeogenesis Flashcards
(145 cards)
1
Q
gluconeogenesis is the biosynthesis of new
A
glucose
2
Q
where does gluconeogenesis occur
A
mostly liver
a little bit kidney
3
Q
when is kidney involved in gluconeogenesis
A
after llong starvartion, more than 48 hours
4
Q
what provides the liver energy to fuel gluconeogenesis
A
ß oxidation of fatty acids
5
Q
the high rate of a.a. metabolism in liver generates
A
urea
6
Q
what happens to the urea the liver generates
A
mvoes to kidney for excretion
7
Q
draw out the chart of effects of gluconeogenesis
A
pg 3
8
Q
the _____ realeased from adipose tissue is used by the liver for gluconeogenesis
A
glycerol
9
Q
skeletal mucsle does not have what enzyme
A
glucose 6 phosphatase
10
Q
because skeletal muscle does not have glucose 6 phosphatase, what does it do with gluconeogenesis
A
it cannot deliver free glucose to blood, so it just does gluconeogenesis to generate glucose for storage as glycogen
11
Q
draw out gluconeogenesis
A
pg 4
12
Q
name three starter compounds for gluconeogensis
A
lactate
glycerol
alanine
13
Q
lactate and alanine are turned into what to be used for gluconeogenesis
A
pyruvate
14
Q
how is lactate turned into pyruvate
A
oxidized
15
Q
how is alanine turned into pyruvate
A
transaminated
16
Q
pyruvate is converted to what to be used for gluconegoenesis
A
oxaloacetate
17
Q
oxaloacetate is converted to what to be used for gluconegenesis
A
phosphoenol pyruvate
18
Q
what sugars can be used as precurser for gluconeogenesis
A
pyruvate
lactate
oxaloacetate
19
Q
what protein can be used as precurser for gluconeogenesis
A
alanine - can be converted to TCA intermediates
20
Q
animals cannot produce glucose from
A
fatty acids
21
Q
what catalyses pyuvate → oxaloacetate
A
pyruvate carboxylase
22
Q
what is needed in the reaction of converting pyruvate to oxaloacetate
A
ATP
biotin
23
Q
what catalyzes the reaction of oxaloacetate to phosphoenolpyruvate
A
PEP carboxylase
24
Q
inhibition of what is essential when turning pyruvate into oxaloacetate
A
pyruvate dehydrogenase
25
biotin helps trap
HCO3-
26
biotin trapping HCO3- is helpful for what kind of reactions
carboxylation
27
how is biotin attached to pyruvate carboxylase
amide bond to lysine residue
28
where does pyruvate → oxaloacetate occur
in mitochondria
29
deficiencies of biotin affect mainly
fatty acid biosynthesis
30
the first gluconeogenic step stravels through
mitochondria
31
oxaloacetate can be converted to what in mitochondria and what does this allow?
malate
| malate can travel through the mitochondria into cytosol for gluconeogenesis
32
besides malate what else can travel through mitochondria
PEP
33
besides turning into malate what else can oxaloacetate turn into
PEP
34
draw out the two pathways for oxaloacetate turning into malate & PEP
pg 10
35
ethanol inhibits
gluconeogenesis
36
how does ethanol inhibit gluconeogenesis
alters NAD+/NADH ratio
37
alcohol consumption results in high levels of
NADH/NAD+
38
with high levels of NADH/NAD+ what happens to pyruvate
reduced to lactate
39
what is final result of ethanol making high NADH/NAD+ ratio
lactic acidosis
40
high acetyl CoA reflects high
energy charge
41
acetyl CoA can allosterically activate
pyruvate carboxylase
42
acetyl CoA promotes
gluconeogesnsis
43
not only does Acetyl CoA activate pyruvate carboxylse, it inhibits
PDH
44
what inhibits PDH
Acetyl CoA
45
Acety CoA is produced by
ß oxidation
46
basically if there is high Acetyl CoA it is a signal that
cell has enough energy to fuel gluconeognesis
47
what two functions arise in starving state
urea synthesis
ketogenesis
(pg 12)
48
draw out acetyl coA affect on gluconeogenesis (on oxaloacetate and pyruvate)
pg 13
49
what does PDH stand for
pyruvate dehydrogenase
50
what inhibits PDH
ATP
NADH
Actyl CoA
51
absolute control of glucose oxidation is mediated by availability of what
NAD+
52
when is NADH converted back to NAD+
ox phos
53
Oxidation of glucose is diminished when ketoacids in the brain or fatty acids in skeletal muscle are oxidized
why is this?
when they are oxidized it steals NAD+ so NAD+ isn't available for oxidation of glucose
54
what is the cost of going through gluconeogenesis
4 ATP
2GTP
2NADH
55
why is gluconeogenesis necessary
brain
RBC
nervous system
they all NEED glucose for energy
56
gluconeognesis can generate glucose from a.a. but NOT
fatty acids
57
how is glucose 6 phosphate transported out of liver
dephosphorylated
58
where is glucose 6 phosphatase
ER lumen
59
glucose production in liver requires two proteins only found in gluconeogenic tissue:
glucose 6 phosphate translocase
| glucose 6 phosphatase
60
what point connects glycolysis and gluconeogenesis
glucose 6 phosphate translocase
| glucose 6 phosphatase
61
draw out G6P leaving liver
pg 15
62
pyruvate kinase is inactivated by phosphorylation by
PKA
| glucagon signaling
63
what is enzyme for Fructose 1,6-bisphosphate → fructose 6-phosphate
fructose bisphosphatase-1
64
does Fructose 1,6-bisphosphate → fructose 6-phosphate
| make TP?
no
65
what is enzyme for Glucose 6-phosphate → glucose
glucose 6 phosphatase
66
does Glucose 6-phosphate → glucose
| make ATP?
no
67
glucagon effects gluconeognesis by what three mechanisms
Changes in allosteric effectors (2,6-bisphophoglyceate)
Covalent modification of enzyme activity (pyruvate kinase)
Induction of enzyme synthesis (PEPCK)
68
what controls the amount of F26BP
insulin & glucagon
69
what does insulin do to F26BP
promotes
70
what does insulin promote
glycolysis
71
what does insulin inhibit
gluconeognessi
72
what does glucagon do to F26BP
decreases it
73
glucagon promotes
gluconeogenesis
74
glucagon inhibits
glycolysis
75
draw out the regulation of glucagon and insulin and glycolysis/gluconeogenesis
pg 18
| you drew this last block too. don't forget PFK -2 and FBP 2
76
F26BP activates PFK-1 by
increasing its affinity for fructose 6 phosphate
77
FBPase-1 is inhibited by
F26Bp
78
PEP is only used for production of
glucose
79
glucagon via PKA inactivates
pyruvate kinase
80
draw out glucagon affect on pyruvate kinase
pg 20
81
FOX01 is a
transcription factor
82
what does insulin do to FOX01
turns it off
83
in the cytosol FOX01 is phosphorylated by
PKB
84
phosphorylated FOX01 is then tagged
by ubiquitin → degradation in proteasome
85
what does FOX01 transcribe
PEP carboxykinase
| Glucose 6 phosphatase
86
draw out insulin effect on FOX01
pg 21
87
what is the ultimate effect of insulin on FOX01
turns off transcription of PEP carboxykinase and glucose 6 phosphatase
88
during prolonged fasting, gluconeogenesis is induced. what key enzymes are activated during this time
glucose 6 phosphatase (G6Pase), fructose 1,6-bisphosphatase (Fbpase), pyruvate carboxylase (PC), and phosphoenolpyruvate carboxykinase (PEPCK)
89
the expression of enzymes for gluconeogenesis is activated by
glucagon
| stress hormone cortisol
90
glucagon and cortisol act on what key transcription factors
cAMP response element binding protein (CREB)
| FoxOs
91
list the steps for glucagon to induce PEPCK
Glucagon → PKA → CREB → PGC-1α → Fox01 → PEPCK
92
what decreases expression of PGC-1α
insulin
93
what does PGC-1α do
upregulates ALA synthase
94
draw out insulin and glucagon, fasting vs. feeding and the TF they alter
pg 22
95
why can we produce glucose from so many a.a. intermediates? (see pg 7)
they are all intermediates of TCA cycle, so can all get to oxaloacetate
96
compare and contrast a meal of glucose vs. meal of protein and how they affect glucose insulin and glucagon
after glucose meal: insulin and glucose levels rise, glucaon levels fall. after about two hours the insulin and glucose levels drop off
after protein meal: glucose levels dont change. insulin level rise slightly and remain constant, don't drop off after 2 hours. glucagon rise slightly and remain constant.
97
exercise leads to the production of what two things that activates liver gluconeogenesis
alanine & lactate
98
draw out the glucose alanine cycle
pg 25
99
draw out the glucose lactate cycle
pg 25
100
the glucose alanine cycle is used primarily for what purpose
for skeletal muscle to eliminate nitrogen during exercise and replenish the energy supply
101
glucose lactate cycle is used for what purpsoe
recycles lactate produced by muscle during anaerobic metabolism
produces glucose via gluconeogenesis in liver
102
glucose oxidation produces
pyruvate
103
pyruvate can undergo transamination and become
alanine
104
pyruvate to alanine is catalyzed by
alanine transaminase
105
what is 100% needed to turn lactate to glucose
gluconeogenesis
106
in type II diabetes, what is difference in mellitus gluconeogenesis
it is 3x faster than in non-diabetic pt
107
list the two main functions of gluconeogenesis
maintain glucose levels
| remove lactate from tissues, esp the ones that are constantly producing lactate like RBC
108
what drugs have been used to inhibit gluconeogenesis, lowering glucose for pts with diabetes mellitus type I and II
Metformin & phenformin
109
what does ALT stand for
alanine transaminase
110
glucose and glutamine go to what intestinal cell from teh blood supply
intestinal enterocytes
111
what serves as the major substrate for intestinal gluconeogenesis
carbon atoms of glutamine
112
draw out the pathway once glucose and glutaine enter intestinal enterocyte
pg 27
113
what happens to 2-oxoglutarate, made from glutamine
it is turned into oxaloacetate
114
in small intestine ,after 2-oxoglutarate is turned into oxaloacetate what happens
converted to PEP (phosphoenolpyruvate)
115
PEP stands for
phosphoenolpyruvate
116
in small intestine, PEP is diverted to
gluconeogenic pathway
117
when glucose enters enterocyte, what happens
glycolsysis → pyruvate → reduced to lactate or transaminated to alanine → gluconeogenic substrate in liver
118
what serves as the major precursor of glucose in small intestine
glutamine
119
the presence of G6Pase in SI plays a role in export of
glucose to portal circulation
120
gluconeogenesis in the kidney allows disposal of
acid in metabolic acidosis
121
Increased renal catabolism of glutamine is facilitated by increased expression of
```
genes that encode glutaminase (GA)
glutamate dehydrogenase (GDH)
phosphoenolpyruvate carboxykinase (PEPCK)
apical Na+/H+ exchanger (NHE3)
SNAT3
```
122
increased expression of NHE3 contributes to transport of
ammonium ions
123
Increased expression of NHE3 contributes to acidification of
luminal fluid
124
The combined increases in renal ammonium ion excretion and gluconeogenesis result in a net synthesis of
HCO3− ions
125
HCO3− ions are transported across basolateral membrane by what
Na+/3HCO3− cotransporter
126
in diabetes type 2 what is out of control
gluconeogenesis
127
what is happening to liver in type 2 diabetes
1) Fatty liver (steatosis)
2) Inflammation
3) Insulin resistance
4) ↑Fatty acid biosynthesis
5) ↑ gluconeogenesis
128
what is happening to muscle in type 2 diabetes
insulin resistance
| glucose uptake and utilization
129
the increased gluconeogenesis and insulin resistance results in what in type 2 diabetes
hyperglycemia & hyperinsulinemia
130
what does metformin do
lowers liver gluconeogenesis
131
draw out metformin affect on gluconeogenesis
pg 30
132
why do we need 2 pyrvate to do gluconeogenesis
glucose is 6 carbon and pyruvate is 3 carbon
133
pyruvate kinase is activated by
F16BP
134
pyruvate kinase is inhibited by
ATP, alanine, glucagon & epinephrine, PKA
135
phosphofructokinase is activated by
F26BP
136
phosphofructokinase is inhibited by
ATP
| Citrate
137
describe the role of fructose 2,6 bisphosphate in regulating glycolysis and gluconeogenesis
pg 19
138
gluckinase is induced by
insulin
139
describe glucose and glucokinase km
very high (so not high binding affinity)
140
pyruvate carboxylase is activated by
Acetyl-CoA
141
phosphoenolpyruvate kinase is induced by
glucagon
epinephrine
glucocorticoids
142
phosphoenolpyruvate kinase is repressed by
insulin
143
Glucose 6 phosphatase is induced during
fasting
144
what inhibits glucose 6 phosphatase
F 2,6 BP
| AMP
145
what does adenylate kinase do
converts ADP to ATP + AMP
