Gluconeogenesis (midterm) Flashcards
Gluconeogenesis is creating new glucose from….
non-carbs
What are the 5 substrates for gluconeogenesis?
1) glucogenic AAs
2) glycerol
3) pyruvate
4) lactate
5) intermediates of TCA
Which AAs are glucogenic?
ALL standard AAs EXCEPT lysine and leucine (so theres 18 glucogenic AAs)
this means these AAs can change to glucose
Muscles that are breaking down for protein is a major substrate for gluconeogenesis. Which muscles breakdown first?
skeletal muscles that are not used or infrequently used are broken down to get glucogenic AAs for gluconeogenesis
How are the intermediates from TCA cycle used in gluconeogenesis?
Glucogenic AAs (everything besides lys and leu) can have the amino group removed and become an intermediate for TCA, which will then allow it to become glucose
ex: aspartate can change to OAA and then go through malate shuttle
How long does glycerol last and where is it found?
12 hours and is found in fats/TG
T/F: you get lactate from RBCs if you don’t exercise, and if you do exercise then lactate also comes from skeletal muscle
true
Is this an oxidation reaction or reduction reaction?
pyruvate to lactate with LDH
reduction reaction
Is this an oxidation reaction or reduction reaction?
lactate to pyruvate with LDH
oxidation reaction
Glycogen is in the _____________ of liver. It can change to blood glucose
cytoplasm
where does gluconeogenesis occur?
in mitochondria and cytoplasm of liver
Which 2 enzymes are used in both glycogenolysis and and gluconeogenesis?
G6Pase and F1,6BPase
There are 3 rate limiting steps in glycolysis. So in gluconeogenesis, it has to bypass all 3 rate limiting steps/enzymes. What are the 3 steps of glycolysis and RLEs?
step 1 of glycolysis with GK or HK
step 3 with PFK1
step 10 with pyruvate kinase
What is required in gluconeogenesis to make 1 glucose?
-2 pyruvate
-6 ATP
-2 NADH
What is gluconeogenesis stimulated by?
-glucagon
-hypoglycemia
-fasting
T/F: gluconeogenesis is essentially the glycolytic pathway in reverse
true
What are the 4 key enzymes in gluconeogenesis?
1) pyruvate carboxylase
2) PEP carboxykinase
3) F1,6BPase
4) G6Pase
all other enzymes are the same as in glycolysis
Is gluconeogenesis an anabolic or catabolic reaction?
anabolic
What pathways are most commonly involved in gluconeogenesis?
reverse glycolysis and TCA
Which enzyme is only found in liver mitochondria and is why gluconeogenesis is in both mitochondria and cytoplasm?
pyruvate carboxylase
First bypass of gluconeogenesis is 2 steps. What is the first step?
Pyruvate gets converted to OAA with pyruvate carboxylase (ABC enzyme)
note: this step requires biotin, 2 ATP, and carbon dioxide
First bypass of gluconeogenesis is 2 steps. What is the second step?
OAA gets converted to PEP with PEP CK
note: 2 GTP is required and the reaction will release carbon dioxide
Pyruvate has 2 ways to enter the TCA. What are they?
1) convert to acetyl CoA with pyruvate dehydrogenase (glycolysis/TCA)
2) convert to OAA with pyruvate carboxylase (gluconeogenesis)
Where is PEP CK located?
in both cytoplasm and mitochondria
Is PEP a VIP molecule?
yes
2 pyruvate are used to make one glucose. What energy sources are needed to do this?
6 ATP (4 ATP, 2 GTP) and 2 NADH will be used to convert 2 pyruvate to 1 glucose
2 glycerol 3 phosphates are used to make one glucose. What energy source is made?
2 NAD+
2 lactates are converted to 2 pyruvate, which then makes 1 glucose. What energy is needed to do this?
lactate to pyruvate makes 2 NADH
pyruvate to glucose uses 6 ATP and 2 NADH
so the net energy LOSS is -6 ATP (was used)
How much ATP is required for first bypass of gluconeogenesis?
2 ATP, 2 GTP (so 4 ATP)
When cytosolic NADH levels are high, PEP is generated in the….
mitochondria
What is the 2nd bypass of gluconeogenesis?
This reaction bypasses reaction 3 of glycolysis (catalyzed by PFK1)
What is the 3rd bypass of gluconeogenesis?
1 glucose makes 2 pyruvate. What energy sources are made?
2 ATP, 2 NADH
To prevent the waste of a futile cycle, glycolysis and glucoenogenesis are….
reciprocally regulated
At the first control point of glycolysis/ gluconeogenesis, If the energy demands of the cell are being met, the TCA cycle slows and __________ will accumulate
acetyl CoA
High concentrations of acetyl coa inhibits _______ and activates _______
pyruvate dehydrogenase (PDH) and pyruvate kinase, pyruvate carboxylase (PC)
What is the most important control step for gluconeogenesis?
2nd control step, to bypass PFK1 in glycolysis
this is done with F1,6 biphosphatase
this step is regulated by 2 mechanisms:
-indicators of cell energy demand
-hormones
The second control step in gluconeogenesis is bypassing PFK1 with F1,6 BPtase. One of the mechanisms to regulate this is indicators of cell energy demand. What would elevated AMP do?
stimulate PFK1 but inhibit F1,6 BPtase
When ATP is low, AMP is high, the cell does not expand energy in synthesizing glucose
The second control step in gluconeogenesis is bypassing PFK1 with F1,6 BPtase. One of the mechanisms to regulate this is indicators of cell energy demand. What would elevated ATP do?
inhibit PFK1, stimulate F 1,6 BPtase
when cellular ATP is high, AMP is low, glucose is not degraded to make ATP
The second control step in gluconeogenesis is bypassing PFK1 with F1,6 BPtase. One of the mechanisms to regulate this is indicators of cell energy demand. What would elevated citrate do?
inhibit PFK1, stimulate F1,6 BPtase
What 2 molecules inhibit PFK1 but stimulate F1,6 BPtase?
high ATP and citrate levels
What hormones enhance gluconeogenesis by removing the inhibitory effects of F2,6 BP?
glucagon or epi
When insulin increases, what 2 pathways are stimulated and 2 inhibited?
stimulated= glucogenesis and glycolysis
inhibited= glycogenolysis and gluconeogenesis
When glucagon increases, what 2 pathways are stimulated and 2 inhibited?
stimulated= glycogenolysis and gluconeogenesis
inhibited= glucogenesis and glycolysis
When ATP increases, what 2 pathways are stimulated and 2 inhibited?
stimulated= glucogenesis and gluconeogenesis
inhibited= glycogenolysis and glycolysis
When ADP/AMP increases, what 2 pathways are stimulated and 2 inhibited?
stimulated= glycogenolysis and glycolysis
inhibited= glucogenesis and gluconeogenesis
Glucagon and insulin will always overpower…
ATP and ADP
