Gluconeogenesis Flashcards
What is gluconeogenesis?
Making on new glucose
Which organs uses glucose as an energy source?
Brain, testes, erythrocytes and kidney medulla
Can glycosis and gluconeogenesis occur at the same time?
No, because its a futile cycle
When does glycosis takes place?
In the well fed state, 4-5 hours after a meal
When dos gluconeogenesis takes place?
After 4-5 hours in between meals
The brain can also get energy from another source
Ketone bodies, after 1-2 weeks without glucose so only under extreme conditions
What are the other ways in which the body can get glucose from?
Alpha keto acids, glycerol, lactate and pyruvate,
What is the first source of glucose in the body?
Liver, lasts 10- q8 hours in the absence of dietary intake of carbohydrates.
What is the second source of glucose?
Gluconeogenesis
Gluconeogenesis requires both mitochondrial enzymes and cytosolic enzymes
The first half occurs in the mitochondria while the second half occurs in the cytosol
How many enzymes are needed to bypass the 3 rate limiting steps?
4
Glycerol, lactate and the alpha keto acids are obtained from
Transamination of glucose amino acids.
The first irreversible step in GLYCOSIS is the
Phosphoenolpyruvate to pyruvate by pyruvate kinase
What is the enzyme that converts pyruvate to oxaloactate.
Pyruvate carboxykinase
Where is carboxylate found
Mitochondria
What is the cofactor in the carboxylation of pyruvate?
Biotin. Biotin is bound to apoenzyme of pyruvate carboxylase through an delta amino group of a lysylresidue to form biocytin
Can pyruvate come from alanine?
Yes
Oxaloactate can not leave the mitochondria so it must be converted to?
Malate by maleate dehydrogenase
In the cytosol malate is reoxidised to oxaloactate converted back to PEP by
Phosphoenolpyruvate carboxykinase
What is the first bypass state in gluconeogenesis ?
Carboxylation of pyruvate
OAA is converted to PEP by
Pep- carboxykinase using hydrolysis of GTP
PEP is converted to Fructose 1, 6 bisphosphate by
Glycolytic reactions that occur in the opposite direction in glycosis.
What is the allosteric regulator in decarboxylation reaction
Fructose 2,6 phosphate
The enzyme fructose 1,6 bisphosphatase used in the conversation of ………………. Instead of the enzyme
Fructose 1,6 bisphosphate to fructose 6 phosphate instead of phosphofructokinase.
How is gluconeogenesis regulated?
By energy levels of AMP in the cell, fructose 1,6 bisphosphatase is inhibited and regulator. By fructose 2,6 bisphosphate
High levels of ATP is a signal of?
Energy poor state of the cell.
Regulation of fructose 2,6 bisphosphate
Fructose 1,6 bisphosphatase is inhibited by fructose 2,6 bisphosphate.
Where is the enzyme fructose 2,6 bisphosphate is found?
Liver
When epinephrine or glycagon is secreted when happens?
cAMP is produced
cAMP dependent protein kinase is activated
This phospholates PFK2 and f2,6BPase activity
PFK2 is inhibited and F2,6BPase is activated
F2,6 breaks down and not inhibit F2,6 Bpass and glycosis is broken down
In the absence of epinephrine or glycagon stimulation
cAMP is broken down
cAMP dependent protein kinase
PFK2 is activated and F2,6BPASE is inactivated
F2, 6 BP whose presence stimulates glycosis and inhibits gluconeogenesis .
What happens when there are high levels of fructose 2,6 bisphosphate
Activate glycolysis
Low levels of fructose 2,6 bisphosphate
Activation of gluconeogenesis
What enzyme converts glucose 6 phosphate to glucose
Glucose 6 phosphase , found in the kidney and liver but not muscle like pyruvate carboxylate
Can muscles produce glucose by gluconeogenesis
No
What disease occurs when there is a deficiency of the enzyme glucose 6 phosphatase ?
glycogen storage disease type 1: Von gierke’ disease
Type b glycogen 6 phosphate disease is named?
Glucose 6 phosphate translocation deficiency.
Glycogen storage diseases
Inherited deficiency of glucose 6 phosphatase characterized by severe fasting hypoglycemia because glucose is unable tobe produced from eo ther gluconeogenesis or glycogenolysis
Regulation of gluconeogenesis is determined by the
Circulation of glycagon, availability of gluconeogenesis substrates and allosteric activation by acetyl Co A.
Activation by glycagon occurs in two ways
Changes in allosteric effectors ( lowers levels of fructose 2,6 bisphosphate)
Covalent modification of enzyme activity ( elevates cAMP levels)
Gluconeogenesis rate is affected by availability of precursors especially
Glucose id amino acids
Decrease insulin levels mobilize amino acids from muscles to provide
Carbon skeletons for gluconeogenesis
What allosteric activates hepatic pyruvate carboxylate during starvation
acteyl CoA
What are the sources of glucose
Alfa keto acids , lactate, glycerol found in adipose tissues .
What enzyme metabolize glycerol in the liver?
Glycerol kinase , from glycerol to glycerol phosphate
Glycerol phosphate is oxidized by glycerol phosphate dehydrogenase to
Dihydroxyacetone
Cori cycle
The cycling of lactate and glucose between peripheral tissue and liver
Deceive the cori cycle?
Blood borne glucose is converted by exercising muscles to lactate which diffuses in the blood. The liver takes up the lactate and reconverts it to glucose which is released into the normal circulation. Lactate dehydrogenase in the liver converts lactate to oxaloactate to PEP via gluconeogenesis .
An increase in alanine in the muscle causes the release of alanine from muscle which will then go to
Into the liver and be converted glucose and then go to the muscle
How many ATP are needed to synthesis one mole of glucose from pyruvate in gluconeogenesis ?
12 ATP
In step 1 the glycolysis enzyme is ………. While the gluconeogenesis enzyme is
Hexokinase or glucokinase and glucose 6 phosphate
Step 3.
Phosphofructokinase ………, fructose 1,6 bisphosphatase
Step 9
Pyruvate kinase ……… Pyruvate carboxylase and PEPCk
PC is activated by
Acetyl COA and ADP
PEP ck synthesis is increased
Glycagon and ADP
F 1,6 BPase is inhibited by
f2, 6 BP and AMP
F 1,6 BPase
Citrate and glucagon
