lecture 11 gluconeogenesis Flashcards
what is gluconeogenesis?
creates new glucose molecules using noncarbohydrate precursors such as lactate, pyruvate, and some amino acids which can be converted into pyruvate
which organ is primarily responsible for creating new glucose?
liver
what’s the cori cycle?
Lactate as a precursor can come from the working muscle to the liver via the blood and liver returns glucose via the blood
what is glucose synthesized from?
pyruvate. Noncarbohydrate precursors of glucose are first converted into pyruvate or enter the pathway at later intermediates
Most of the decrease in free energy in glycoly- sis takes place in the three essentially irreversible steps catalyzed by ___
hexokinase, phosphofructokinase, and pyruvate kinase.
what happens to the 3 irreversible (large negative delta G) steps in glycolysis during gluconeogenesis?
these steps must be bipassed
1st step of gluconeogenesis- how do you create PEP?
Carboxylation of pyruvate in the mito matrix to form oxaloacetate
step 2 gluconeogenesis; what happens with oxaloacetate?
(OA -> PEP : remove COO-, phosphorylate. Large negative delta G) OA is decarboxylated. This step has enough free energy to allow a phosphate group to attach to the 3-carbon fragment, forming PEP.
after you create PEP what happens?
all steps are simply reversed until you reach Fructose, 1,6 bisphosphate
what happens once you reach fructose 1,6 bisphosphate?
Fruc 1,6 BP – remove PO3 group. Turns into fruc 6 phosphate
fruc 6 phosphate –> glucose?
convert fruc 6 phosphate into a glucose via ‘isomerase’ ; now its glucose-6-phosphate (theres a phosphate at the 6 position of a regular glucose molecule) glucose-6-phosphatase removes one phosphate from G6P to create glucose (hexokinase cannot be reversed)
The formation of oxaloacetate by pyruvate carboxylase occurs in the ____
mitochondria
how is oxaloacetate shipped into the cytoplasm if there is no transporter for it?
reduced to malate, shipped out, and then reoxidized to oxaloacetate with the generation of cytoplasmic NADH
why do we want oxaloacetate in the cytoplasm?
all glycolytic enzymes are located in the cytoplasm
The generation of free glucose occurs only in the ___because no other cell type has the phosphatase enzyme.
liver
what turns glucose-6-phosphate into glucose to finish gluconeogenesis?
glucose-6-phosphatase- removes the phosphate group to make it normal free glucose
where does glucose-6-phosphatase live?
in the ER on the lumen side
based on glucose-6-phosphatase’s location, how do you finish gluconeogenesis to create free glucose?
Glucose 6-phosphate must be transported into the lumen of the endoplasmic reticulum for the reaction to take place. Then, glucose is shipped back to cytoplasm and by facilitated transport sent back to blood
how many ATP equivalents are used in gluconeogenesis
6
overall gluconeogensis reaction
___high transfer potential phosphoryl groups are spent in synthesizing glucose from pyruvate
six
how is gluconeogenesis regulated?
If energy charge is low, glycolysis predominates. If glucose is low, gluconeogenesis is active.
do glycolysis and GNG occur at the same time?
no, its one or the other, and it depends on current levels in the cell; Glycolysis will predominate when glucose is abundant, and gluconeogenesis will be highly active when glucose is scarce.
what are the 3 points in glycolysis/GNG where they are regulated to determine which path will proceed?
surprise surprise, the 3 irreverisble steps! you’d need to stop those 3 enzymes from working in either case- either to prevent glycolysis or prevent GNG
energy charge of cell; ATP-generating (catabolic) pathways are inhibited by a ___ (high/low) energy charge
AMP is the signal for ___ (high/low) energy state
high
high charge, lots of ATP, tells cell ‘stop making atp’
- low
Substrates for gluconeogenesis come from ___, ___ or ___ that can be converted into glycolytic intermediates.
pyruvate, amino acids or lactate
___ produced by muscle during contraction is released into the blood. Liver removes the lactate and converts it into glucose, which can be released into the blood
lactate
who puts CO2 onto pyruvate to form oxaloacetate( hint its a vitamin)
biotin
how do we go from pyruvate -> PEP since we can’t use pyruvate kinase?
form oxaloacetate as an intermediate. add COO- then decarboxylate it in an energy rich reaction to form PEP. GTP-> GDP to add energy
why is oxaloacetate shipped into cytoplasm
carboxylation of pyruvate only occurs in matrix, however, all necessary enzymes are in cytoplasm. solution: ship OA to the cytoplasm. but no transporter for it in mito membrane- however, there is a transporter for malate, so we bring it out as malate and then reconvert it to OA, to then decarboxylate it to PEP
what’s special about the last step of gluconeogensis (G6phosphatase to gluose)?
highly regulated, only gets dephosphorylated in times of need for glucose
enzyme is hiding in ER lumen. only in kidney/liver. doesnt automatically remove phosphate from glucose so that we can control G6P buildup
pyruvate carboxylase
first step of GNG. turns pyruvate into OA
