Biochem Ch. 14 Gluconeogenesis

Biochem Ch. 14 Gluconeogenesis

The conversion of pyruvate and related three and four carbon non-carbohydrated compounds to glucose
gluconeogenesis
Gluconeogenesis is what type of pathway? catabolic/anabolic?
anabolic (very energy expensive)
The important precursors in animals are
three carbon compounds such as:
-lactate
-pyruvate
-glycerol
-certain amino acids
Where does gluconeogenesis take place in mammals?
-liver
-renal cortex
-epithelial cells that line the inside of the small intestine
Describe the Cori cycle
-glucose is degraded by glycolysis to lactate in muscle
-the lactate is excreted into the blood and returns to the liver
-the lactate is converted back into glucose by gluconeogenesis in the liver
Gluconeogenesis overlaps glycolysis in _____ of 10 steps
seven
Which reactions are common to both the glycolysis and gluconeogenesis pathways?
the reactions that occur with delta G = 0
What are the three reactions of glycolysis that are essentially irreversible in vivo and cannot be used in gluconeogenesis?
1. the conversion of glucose to glucose 6-phosphate by hexokinase
2. the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate by phosphofructokinase-1
3. the conversion of phosphoenolpyruvate to pyruvate by pyruvate kinase
Since the reactions in the previous are not reversible, three bypass reactions occur. Name the three bypass reactions
1. Pyruvate is reactivated using ATP and GTP
2. The two phosphates from fructose 1,6 bisphosphate are released by a phosphatase with loss of energy
3. No ATP is regenerated
ATP is associated with ______ pathways
GTP is associated with ______ pathways
ATP—>catabolic
GTP—>anabolic
In gluconeogenesis, the three irreversible steps are bypassed by a separate set of enzymes, catalyzing reactions that are sufficiently ________ to be effectively irreversible in the direction of glucose synthesis
exergonic
Both glycolysis and gluconeogenesis are __________ processes in cells
irreversible
In animals, glycolysis and gluconeogenesis occur largely in the
cytosol
How is separate regulation of the glycolytic and gluconeogenetic pathways brought about?
Through controls exerted on the enzymatic steps unique to each
There are two pathways to reactivate pyruvate into PEP. These are based on the
reduction potential of the cell
The choice between the two pathways of gluconeogenesis depends on
the redox state of the cytosol
If pyruvate is derived from an oxidized source, like alanine, then activation involves the production of
NADH
If pyruvate is derived from lactate, then NADH is derived from the conversion of lactate to pyruvate and a _______ is unneccesary
reducing step
The choice between the two pathways is made through
compartmentalization between the cytosol and the mitochondria
What happens with pyruvate in both pathways, regardless
pyruvate is imported into the mitochondria and converted into oxaloacetate
If cytosolic reducing potential is required, the oxaloacetate is converted to ________, if not, then it is converted to ______.
malate
PEP
Amino associated pyruvate
alanine
How do we make a 3 carbon molecule into a 4 carbon molecule?
We take carbon dioxide from the cytosol and sequester it
A mitochondrial enzyme that requires the coenzyme biotin, converts the pyruvate to oxaloacetate
pyruvate carboxylase
A B-vitamin previously known as Vit H, is a conenzyme involved in the transfer of carboxylate
Biotin (it takes a fully oxidized carbon and moves it around)
The antimicrobial proteins ______ and ________ have an extremely high affinity for biotin
avidin
streptavidin
Biotin covalently linked to Lys is known as
biocytin
The first regulatory enzyme in the gluconeogenic pathway, requiring acetyl-CoA as a positive effector
Pyruvate carboxylase
Produced by fatty acid oxidation, its accumulation signals the availability of fatty acids as fuel
Acetyl-CoA
Required for control of gluconeogenesis but cannot contribute to the production of glucose
lipids
When deprived of glucose, muscle and fat tissue use the fatty acids of stored ________ as their principal fuel.
triacylglycerols
In the liver, acetyl-CoA derived from this fatty acid breakdown is converted to ________ which are exported and carried to other tissues to be used as fuel
ketone bodies
What are two types of ketone bodies?
acetoacetate
hydroxybutyrate
Critical to the brain, which uses them as alternative fuel when glucose is unavailable
Ketone bodies
Conversion of oxaloacetate to PEP occurs primarily in __________, converting lactic acid and other carbon sources to glucose to maintain blood glucose levels
hepatocytes
If alanine is the carbon source for pyruvate, which enzyme is utilized?
cytosolic PEP carboxykinase, because it is not yet oxidized
When glucose is depleted by aerobic respiration, what do gluconeogenic tissues use to regenerate glucose
oxidized materials
Pyruvate enters the mitochondria and is converted into
oxaloacetate
The mitochondria do/do not have an oxaloacetate transporter?
They do not, therefore, oxaloacetate is reduced to malate and exported (to get it across the membrane)
Once in the cytosol, malate is used to generate
NADH
oxaloacetate
Converts oxaloacetate into PEP using GTP (converts from the cytosolic form to the mitochondrial form)
cytosolic PEP carboxykinase
When lactic acid builds up due to anaerobic respiration, lactic acid is converted to ______ generating ______
pyruvate
NADH
Since the production of NADH is not needed, then _____________ converts oxaloacetate to PEP which is exported to the cytosol (cytosolic form)
mitochondrial PEP carboxykinase
The very first step in gluconeogenesis is the
conversion of pyruvate to PEP
In gluconeogenesis, the initial activating steps in glycolysis are reversed by the action of
phosphatases
What is final enzyme of gluconeogenesis?
glucose-6-phosphatase
Where does glucose-6-phosphatase reside?
NOT found in the cytosol; it is found on the lumenal side of the endoplasmic reticulum of hepatocytes, renal cells, and epithelial cells of the small intestine
Why is glucose-6-phsophatase not found in the cytosol?
It would short circuit glycolysis
For each molecule of glucose formed from pyruvate in gluconeogenesis, what is required
6 high energy phosphate groups
-4 from ATP
-2 from GTP
Two molecules of NADH
Add coefficients to the following reaction summary to show the net results of gluconeogenesis from pyruvate.

2 pyruvate + 2 NADH + 4 ATP + 2 GTP —>

glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi
The body synthesizes glucose from non-carbohydrate sources via
gluconeogenesis
Entry points for the gluconeogensis pathway
pyruvate
oxaloacetate
dihydroxyacetone phosphate
When glucose is degraded by glycolysis to lactate in muscle, the lactate is excreted into the blood and returns to the liver where it is converted back into glucose by gluconeogenesis. We call this
the Cori Cycle
Enzymes involved in both glycolysis (including lactate formation) and gluconeogenesis
phosphohexose (phosphoglucose isomerase)
lactate dehydrogenase
Enzymes involved only in glycolysis of glucose to lactate
hexokinase
pyruvate kinase
Enzymes involved in gluconeogenesis only
glucose 6-phosphatase
fructose 1,6-bisphosphatase
Muscle is not a gluconeogenic tissue because it lacks
glucose 6-phosphatase
Which of the three steps of glycolysis are essentially irreversible and require a different enzyme in gluconeogenesis than in glycolysis?
Steps 1, 3, 10
Which step of gluconeogenesis is the main negative control point?
Step 8
The conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.
Insulin lowers blood glucose levels, in part by suppressing
gluconeogenesis
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