Gluconeogenesis Flashcards
what is gluconeogenesis?
when is it initiated?
where does it occur?
it is an energy WHAT process? what does it require to occur (2)
gluconeogeneis: formation of glucose from non-carboydrate sources
initated: during periods of starvation and exercise
location: liver
energy consuming process & requires 6 ATP / GTP and source of carbon
* what is the net gain / loss of ATP during: *
a) glycolysis?
b) TCA cycle?
c) cori cycle?
what is the net gain / loss of ATP during:
a) glycolysis: Net 2 ATP gain via susbtrate level phosphorylation
b) TCA cycle: Net 38 ATP gain via oxidative phosphorylation
c) cori cycle: Net 4 loss. Anaerobic
gluceneogenesis is the reversal of glycolysis apart from what?
is the reversal of glycolysis: apart from 3 irreversible reactions that occur
- what two things really important glucose consumers? (2) (apart from skeletal muscle)
- what sources of fuel can brain use ? (2) which does it prefer?
- why does the brain need so much glucose? (3)
- why do we need another way of making glucose when we have glycogen stores in the liver?
glucose consumers:
- brain and erythocytes need glucose !! (glucose can cross the BBB)
brain energy:
- brain can use glucose & ketones (but prefers glucose)
need glucose bc:
-60-70% of glucose in brain is used to make ATP, used to make membrane transport mechanisms working, that are used to make Na/K membrane potential needed for transmission of nerve impulses
- synthesis of NT also requires glucose
- rbc dont have mitochondria: need glucose
why glycogen stores arent enough:
- glycogen stores in liver account for ~ 100g = depleted in 24hrs if not replenished. gluconeogenesis can create glucose from different sources of energy.
to make glucose, you need a source of energy and carbon units.
what are 3 sources of carbon that can be used in gluceoneogenesis?
what are 2 sources of energy that can be used in gluceoneogenesis?
sources of carbon:
- lactate (from muscle - glycolysis). exported to liver can be made into pyruvate as a carbon source
- amino acids - from muscle. (from proteolysis) sent to liver & can be made into pyruvate as a carbon source
- glycerol (from lipolysis). sent to liver
sources of energy:
- ATP (from glycolysis and Krebs cycle)
- fatty acids (but cannot be used as C source !!)
in adipose tissue, the triglycerides are broken down to make glycerol and fatty acids.
what are glycerol and fatty acids used for in gluconeogensis?
gluconeogensis:
glycerol: used as a carbon source
fatty acids: broken down to supply ATP
what is the starting material of gluconeogenesis usually?
what are the 3 steps of glycolysis that are metabolically irrervisble and need to be side stepped to in order to produce glucose in gluconeogenesis?
what are the enzymes used to reverse ^ reactions to get original molecules
gluconeogenesis starting material: pyruvate
3 irreversible steps are in glycolysis:
- *1. Glucose –> glucose-6-phosphate.
2. P + fructose-6-phosphate –> fructose-1-6-bisphosphate.
3. pyruvate -> PEP (** complicated)
enyzmes used to reverse ^^ reactions:
- enzyme = gluocse-6-phosphatase (removes the P)
- enzyme = fructose, 1,-6-biphosphatase
- enzyme = (more complicated -> will come to later)
for gluconeogenesis: to get from pyruvate –> phosphoenolpyruvate (PEP) , what 4 intermediates do u need?
what is the cycle needed?
- to get from from pyruvate –> phosphoenolpyruvate (PEP) need: malate cycle:
- pyruvate + CO2 —> oxaloacctate (via enzyme: pyruvate carboxylase - uses ATP). BUT oxaloacctate cannot leave the mt. so:
- oxaloacctate + NADH + H –> malate + NAD+
- malate leaves the mt, and then gets converted back to oxaloacctate:
* *malate + NAD+ –> oxaloacctate (**via enzyme: cytostolic malate dehydrogenase) - oxaloacctate + GTP (now in cytosol) —> PEP + CO2 (via enzyme: cystolic PEP carboykinase)
in the mechanism of pyruvate –> PEP, the first step produces oxaloacctate. why does oxaloacctate have to be converted to malate?
oxaloacctate has to be convered to malate bc oxaloacctate lacks the transporters in the mitochondtia to leave
malate cycle creates 2 intermediates to get to PEP - what are they?
how many ATPs and GTPs are used in malate cycle to produce PEP?
malate cycle creates 2 intermediates to get to PEP: oxaloacctate & malate
how many ATPs and GTPs are used in malate cycle to produce PEP: 1 ATP & 1 GTP. BUT -> bc pyruvate is 3C, and glucose is 6C the reactions need to be doubled: 2ATPs & 2GTPs
glyclosys versus gluconeogenesis (remember, nearly the reverse ! )
- how many ATPS are generated overall in glycolysis?
- h0w many ATPS/GTPs are consumed in gluconeogenesis?
- how many ATPS are generated overall in glycolysis: 2 ATPs generated overall in glycolyiss
- h0w many ATPS/GTPs are consumed in gluconeogenesis:
- *6 ATPs/GTPs in gluconeogenesis
a) **4 in: pyruvate -> PEP
b) 2 in: 3-phosphglycerate to 1-3biphosphoglycerate
gluconeogenesis from FATs (triglycerides):
- what are fats/triglycerides made from? what can each component be used for in gluconeogenesis?
gluconeogenesis from fats/triglycerides:
- fats are made up of glycerol backbone & 3 fatty acid side chains
- glycerol: can be used as carbon source to make pyruvate (and undergo pyruvate –> PEP)
- fatty acids: cannot be used as carbon source. instead converted to acetyl CoA, which is then used to generates ATP for gluconeogenesis
Acetyl co-A is a product of of fatty acid break down.
how do high levels of acetyl co-a influence gluconeogenesis?
high levels of Acetyl Co-A:
activates pyruvate carboxylase (used in step 1 of malate cycle: drives gluconeogenesis from pyruuvate -> PEP & eventually glucose)
inhibits: pyruvate dehydrogenase complex (prevents pyruvate being turned into acteyl co A & sparing it, leaving for gluconeogenesis)
what is the cori cycle?
cori cycle:
when anaerobic & @ muscle during glycolysis = glucose -> pyruvate -> lactate by lactate deyhdroganse.
lactate goes to liver: oxidised back to glucose by gluconeogensis
glucose sent back to muscle to do work.
repeat xox
no net synthesis of glucose here - just recycling the carbons !
in the cori cycle, why is pyruvate -> lactate instead of going directly to gluconeogenesis?
What does the Cori Cycle allow to occur?
How?
what is the overall net gain / loss of ATP bc of this?
Cori cycle allows anaerboic respiration to occur in muscle tissue: glycolysis -> pyrvuate + 2ATP (net)
- BUT: no oxygen at end of ETC to accept electrons and recycle NAD+ & FAD+ = NO TCA.
- Instead: pyruvate -> lactic acid in muscle
- then: lactic acid transports to liver where: lactic acid - > gluose (gluconeogenesis)
- this costs 6ATP
= overall net loss of 4 ATP
gluconeogensis from glycerol:
what is glycerol converted to? what does this get converted to?
where? (2)
(triglycerides are broken down into 3 fatty acids & 1 glycerol. the 1 glycerol can be used for gluconeogenesis:)
- glycerol is converted to dihydroxyacetone phosphate only in the liver & kidneys
- dihydroxyacetone phosphate then reacts with glyceraldehyde-3-phosphate to produce fructose-1,6, bisphosphate (and from there .. = fructose-6-phosphate -> glucose-6-phosphate -> glucose)
- *specifically, how is** gluconeogensis controlled by:
- insulin?
- glucagon?
- adrenaline?
(.i.e. which enzymes blocked etc)
gluconeogensis controlled by:
insulin:
- inhibits gluconeogensis
- *-** insulin dephosphorylates pyruvate dehydrogenase. this makes pyruvate dehydrogenase active & converts pyruvate -> acetyl coA, which enters krebs cycle. pyruvate is therefore not available to be made into glucose
- glucagon & adrenaline:
- promotes gluconeogensis
- glucagon increases cAMP levels. this causes pyruvate dehydrogenase to be phosphorlayed (by pyruvate dehydrogenase kinase) & inactive. pyruvate is then available for glucose production
