36 Gluconeogenesis Flashcards
what is the Fed state?
glucose available from food, enters blood via gut
what is the Fasting state?
liver uses glycogen store to produce glucose for the body, sends it out to the blood. Some glucose is made from precursors (glycerol, amino acids and/or lacate) also
what is the Starved state?
liver makes glucose from precursors, sends it out to the blood.
what is the making of glucose from precursors called?
gluconeogenesis
how long does it take before glucose is cleared?
within 4 hrs after a meal
what does glycogenolysis supply?
Glycogenolysis supplies glucose in the short term, but does not last much more than 18-24 hrs
what does gluconeogenesis supply?
glucose to the blood over the long term, as long as precursors are available
what is the goal of gluconeogenesis?
synthesize glucose and release to blood to maintain blood glucose level
what is gluconeogenesis?
the synthesis of glucose from non-carbohydrate precursors
where does gluconeogenesis primarily occur?
occurs primarily in the liver because this organ takes care of blood glucose
kidney and adipose (glycolytic intermediates) can do this but for different reasons
how is the gluconeogenic pathway similar to glycolysis?
largely the reverse of glycolysis; 7 of 10 reactions are the same using enzymes that are freely reversible
The three metabolically irreversible reactions of glycolysis are bypassed:
energetically favorable reactions catalyzed by different enzymes
These reactions are metabolically irreversible for glucose synthesis.
T/F, the three metabolically irreversible reactions are highly regulated to ensure glycolysis or gluconeogensis predominates?
T
what are the three enzymes bypass enzymes that are highly regulated in gluconeogenesis?
PEP carboxykinase
fructose bisphosphatase
glucose 6-phosphatase
these enzymes make the pathway a negative delta G reaction
is catabolic oxidative or reductive? glycolysis or gluconeogensis?
oxidative because making ATP, taking electrons out; glycolysis
is anabolic oxidative or reductive? glycolysis or glujconeogenesis?
reductive, putting electrons in for purpose of sending energy out for some other cell to use; gluconeogenesis
what are the three primary carbon sources?
lactate
glycerol
amino acids, particularly alanine which is obtained by the degradation of protein esp muscle
where does lactate come from?
produced by anaerobic glycolysis in exercising muscle or red blood cells
where does glycerol come from?
produced by adipose tissue following liberation of fatty acids
where do the amino acids like alanine come from?
obtained by degradation of protein (esp. muscle)
Alanine is produced from other aas and by glucose
T/F, liver can take lactate up from the blood?
T
where does lactate come from during fasting?
red blood cells
what can gluconeogenesis precursors form?
pyruvate, intermediates of the TCA cycle/glycolysis/gluconeogenesis
how is pyruvate produced from gluconeogenic precursors like lactate and alanine?
LDH, which oxidizes lactate to Py using NAD+ to NADH
how is pyruvate produced from alanine?
Alanine aminotransferase
what does adipose tissue store fat as?
triglycerides and glycerol is the product after fatty acids are nipped off to circulate into the blood and the remaining glycerol (low energy molecule) gets sucked up by the liver
how is glycerol used as a gluconeogenesis precursor?
glycerol is converted to dihydroxyacetone phosphate (DHAP) which is a gluconeogenesis intermediate and can combine with glyceraldehyde 3 phosphate to make F-1,6-bis P
what is the significance of having glycerol kinase?
it converts glycerol to glycerol 3-phosphate which can undergo further processing to feed into gluconeogenesis
what is unique about the glycerol precursor in gluconeogeneis?
so once you have the DHAP and there is no glyceraldehyde 3-P gluconeogenesis can still move forward because you can convert DHAP into the glyeraldehyde 3-phosphate and then proceed onward
in glycolysis, how molecules phosphorylated?
using ATP and kinases
in gluconeogenesis, how are molecules dephosphorylated?
phosphatase which produces Pi
What are characteristics of the Bypass reactions?
Each of these is energetically favorable to drive the reaction forward.
Can’t drive a kinase backwards to produce ATP
Therefore, must bypass kinase steps with one or more reactions
note that too much positive delta G is needed to go straight to PEP so the process is enabled to bypass this step to get where it needs to go (energy exchange through ATP, NADH, GTP)
where do we get lactate from again? Amino acids? what pathway are these used to fuel? what are these converted into that begin the pathway?
the blood; muscle; gluconeogenesis; pyruvate
in terms of the first bypass with pyruvate converting to pep, how is this conversion thermodynamically favorable? what happens if pyruvate kinase were to be active also?
Through use of GTP to GDP by Phosphenol pyruvate carboxykinase (PEPCK) and low amounts of PEP is what propels the reaction forward to glucose
it would take the PEP and convert it back to pyruvate performing a futile cycle, to prevent glucagon is active which phosphorylates the PK to become inactive
why is PEP-CK inducible?
because its need is based on demand by the cell, unregulated when body is in fast state
in terms of conversion, what does pyruvate become? is this reversible? what is the enzyme?
oxaloacetate; no; pyruvate carboxylase
in terms of conversion, what does oxaloacetate become? is this reversible? what is the enzyme?
malate; yes; malate dehydrogenase
what is the conversion of aspartate to and alpha ketoglutarate? are these reversible?
oxaloacetate and glutamate; yes
what is the purpose of fructose-2,6-bisphosphate?
it stimulates glycolysis and so when high it will stimulate phosphofructokinase 1 (PFK-1) and so when insulin is present and glycolysis is dominant fructose 2,6 bisphosphate is working keeping the PFK-1 working and so for gluconeogenesis to work you have to destroy fructose 2,6 bisphosphate via a phosphatase molecule
what makes F-2,6-P? destroys it?
insulin; glucagon (turns off PFK-1) and so as a result F-6-P can convert (isomerize) to G-6-P to supply glucose to the blood
During the third bypass, where is glucose 6 phosphate transported?
ER to phosphatase to make glucose protecting it from glucokinase enzyme from the cytoplasm and so when it does comes out (the glucose) it comes out at low concentrations not to simulate the glucokinase and out to the blood
this is an example of compartmentation for regulation; separation fo glucokinase from glucose 6 phosphatase to prevent futile cycle
how does insulin affect how cells use glucose?
it has to meet its immediate needs then,
- with the excess glucose, liver makes glycogen and FAs
- muscle makes glycogen
- adipose takes in FA and makes/stores TG, this is where glycolysis is essential
what is the effect of excess glucose on adipose tissue?
adipose can produce fats with excess glucose or fats can be imported from the blood. Fats can be repackaged as TGs using glycerol supplied by glycolytic intermediates DHAP to G-3-P
what stimulates phosphofructokinase-1 to drive glycolysis forward? what about pyruvate kinase?
AMP in the muscle because its using ATP and F-2,6-bisP in the liver; F-1,6-bisP
what stimulates insulin to be more active?
more glucose in the blood
what is the step that commits glucose to glycolysis?
the activation of PFK-1 that converts fructose 6-P to fructose 1,6-bis P
What Happens When Blood Glucose Is Needed During Fasting? What pathways become activated?
glycogenolysis and gluconeogenesis
what stimulates glycogenolysis? how does it work in the liver and muscle?
liver glycogen produces glucose for the body and muscle produces glucose for itself
so during fasting, when we need glucose, what is the effect of gluconeogenesis?
making glucose for the blood stream for the brain and RBC
in the first bypass for gluconeogenesis what are the two major enzymes?
pyruvate carboxylase and PEP carboxykinase
in the second bypass what is important to note about enzyme regulation?
one enzyme on, the other off to prevent a futile cycle
