Gluconeogenesis And Glycogen Metabolism Flashcards
What 6 tissues in the body require a continuous supply of glucose as a metabolic fuel?
- Brain
- Red blood cells
- Kidney medulla
- The lens and the cornea of the eye
- Testes
- Exercising muscle
How many grams of glucose does the brain need per day?
120g per day
How much glucose is in the body?
210g in total:
- 190g fro glycogen stores
- 20g circulating in the blood
How long can liver glycogen meet the demands of the body for once there is an absence from dietary input?
10-18 hours
Once glycogen stores are depleted, glucose can be formed from what precursors?
- Lactate
- Pyruvate
- Glycerol
- a-ketoacids
Why is pyruvate to glucose not a reverse of glycoloysis?
- due to the 3 irreversible reactions in glycolysis this cannot occur
- so glucose is then synthesised in a unique pathway
Where does around 90% of gluconeogenesis occur?
90% in the liver. The other 10% of newly synthesised glucose molecules are provided by the kidney
When do kidneys become a major role?
In prolonged starvation, as they will the become a major glucose producing organ
What are 3 unique reactions to gluconeogenesis?
- 3 irreversible reactions
- Bypass reactions
- Other reactions that are a reversal of glycolysis
What are the 3 irreversible reactions in Gluconeogenesis?
- Glucose —> Glucose-6-phosphate
- Fructose-6-phosphate—> Fructose 1,6 biphosphate
- Phosphoenolpyruvate —> pyruvate
What do the 3 bypass reactions involve and what do they do?
Bypass reactions are used to bypass the irreversible reactions
Bypass 1: Pyruvate kinase = 3 steps
Bypass 2: Phosphofructokinase = 1 step
Bypass 3: Hexokinase = 1 step
What is the definition of Gluconeogenesis?
Gluconeogenesis is the formation of glucose from a non-carbohydrate source
What is involved in bypass 1 of Gluconeogenesis?
Bypass 1= Pyruvate —> Phosphoenolpyruvate
Step 1:
Carboxylation of pyruvate.
Pyruvate —> oxaloacetate by the enzyme pyruvate carboxylase
Pyrvate carboxylase is only found in the mitochondria of the liver and kidney cells
Step 2:
Transport of oxalocetate to the cytosol
Oxalocetate is converted into malate by mitochondrial malate dehydrogenase. So it can cross the mitochondrial membrane where it is re-oxidised back into oxalocatete so it can enter the cytosol
Step 3:
Decarboxylation of cytosolic oxalocetate
Reaction driven by hydrolysis of GTP
PEP then enters the reversible reactions of glycolysis until it reaches fructose 1, 6 biphosphate
What happens in bypass 2 of Gluconeogenesis?
- Dephosphorylation of fructose 1,6 biphosphae by hydrolysis.
- Catalysed by enzyme fructose biphosphatase
- important regulatory site of gluconeogenesis
What happens in bypass 3 of glucogeneonesis?
- Glucose-6-phosphate —> glucose
- Hydrolysis of glucose-6-phosphate bypasses the irreversible hexokinase reaction of glycolysis
- glucose 6 phosphatase is present in the liver and kidney but NOT in muscle
Where does glucose 6 phosphatatse and pyruvate carboxylase occur?
In cells of the liver and kidney
What 2 things can contribute to the blood glucose pool?
Liver and Kidney.
What are gluconeogenic precursors?
Molecules that can give rise to a net synthesis of glucose
What do gluconeogenic precursors include?
All the intermediates of glycolysis and the citric acid cycle
What are the most important gluconeogenic precursors?
- Glycerol
- Lactate
- Alpha-ketoacids
What are the key features of the following gluconeogenesis precursor: Glycerol
- released during hydrolysis of triaclglycerols in adipose tissue and is delivered in the blood to the liver
- Glycerol is phosphorylated to glycerol phosphate, then oxidised to the glycolytic intermediate: dihydroxyacetone phosphate
- Dihydroxyacetone phosphate —> Glyceraldehyde-3-phosphate
What are the key features of the following gluconeogenesis precursor: Lactate
- Released into blood by cells that lack mitochondria
- end point of anerobic respiration
- lactate is taken up by liver and converted to glucose which is released back into circulation
What are the key features of the following gluconeogenesis precursor: alpha-ketoacids
- contributes to liver glycogen in liver and muscle
- amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are called glucogenic
What happens when glycogen stores are depleted in the body?
The body synthesises glucose by gluconeogenesis
What does the body store a reserve pool of glucose as?
The body stores a reserve pool of glucose in the form of glycogen
What does the body need a constant store of and is of metabolic importance
The body needs a constant source of blood glucose
What limits the production of glycogen in the body?
It is still unknown
How many grams of glycogen makes up 1-2% of the fresh weight of resting muscle
400g glycogen
100g glycogen makes up the fresh weight of what?
A well fed adult liver
What are 4 features of glycogen structure?
- Branched chain homopolysaccharide made from alpha-D-Glucose
2.Primary glycosidic bonds are alpha 1-4 and between every 8-10 residues there is a branch consisting of an alpha 1-6 glycosidic bond - Molecular weight of <10^8
- Exist as discete cytoplasmic granules containing most of the enzymes for synthesis and breakdown
What is the core of a glycogen granule made from?
And what are the benefits of its structure?
Made from the protien glycogenin and surrounded by branches of glucose polymers
Benefits= more space efficient, there is more glucose in the same space
Where does glycogen synthesis occur and what energy does it need to happen?
Process occurs in the cytosol, requires energy in the form of ATP
Glycogen is synthesised from what molecules?
Alpha-D-Glucose that are initially attached to uridine dihosphate
What is UDP-glucose?
It is glucose attached to uridine diphosphate
What is UDP-glucose the source of?
Source of all glucosyl residues that are added to the growing glycogen molecule
What does step 1 of glycogen synthesis involve?
- Glucose 6-phosphate is converted to glucose 1-phosphate by phosphoglucomutase
What happens in step 2 of glycogen synthesis?
- Synthesis of glycogen primer to initiate glycogen synthesis
- main enzyme involved in gkycogen polymerisation
-glycogen synthase is responsible for making the alpha 1-4 linkages in glycogen - glycogen synthesis requires a primer: glycogenin
What are 3 key features of glycogenin?
- Dimer of 2 identical 37kD units
- Catalyses the addition of glucose to itself by covalently attatching glucose from UDP-glucose to the hydroxyl grou of tyrosine-194 in each subunit
-Autocatalytic reaction facillitated by glycogen initiator synthase activity
Glycogenin also has glucosyltransferase activity, What does this allow for?
The addition of up to 8 glucose residues from UDP-glucose to its partner in the glycogenin dimer in this sequence of autoglycosylations
What happens in step 3 of glycogen synthesis?
- Elongation of glycogen chains by glycogen synthase:
- Transfer of glucose from UDP-glucose to the non-reducing end of the growing chain
- Enzyme responsible for making these alpha 1-4 linkages in glycogen in glycogen synthase
- UDP released when the new alpha 1-4 linkage is formed an be converted back to UTP by nucleoside diphosphokinase
UDP + ATP —> UTP + ADP - Glycogen banching enzymes transfers the end of one chain to an earlier part of the chain by a 1,6 glycosidic bond
- Which one of the following is NOT a characteristic of gluconeogenesis?
a. It requires energy in the form of ATP or GTP.
b. It is important in maintaining blood glucose during the normal overnight fast.
c. It uses carbon skeletons provided by degradation of amino acids.
d. It consists of all the reactions of glycolysis functioning in the reverse direction.
e. It involves the enzyme fructose 1,6-bisphosphatase.
d. It consists of all the reactions of glycolysis functioning in the reverse direction.
- Which one of the following reactions is unique to gluconeogenesis?
a. Lactate —-> pyruvate
b. Phosphoenolpyruvate —> pyruvate
c. Oxaloacetate —> phosphoenolpyruvate
d. Glucose 6-phosphate —> fructose 6-phosphate
e. 1,3-Bisphosphoglycerate —> 3-phosphoglycerate
c. Oxaloacetate —> phosphoenolpyruvate
- Which one of the following compounds cannot give rise to the net synthesis of glucose?
a. Lactate
b. Glycerol
c. -Ketoglutarate
d. Oxaloacetate
e. Acetyl CoA
e. Acetyl CoA
- Which one of the following statements concerning gluconeogenesis is correct?
a. It occurs only in muscle.
b. It is stimulated by fructose 2,6-bisphosphate
c. It is inhibited by elevated levels of acetyl CoA
d. It is important in maintaining blood glucose during the normal overnight fast.
e. It uses carbon skeletons provided by the degradation of fatty acids.
d. It is important in maintaining blood glucose during the normal overnight fast.
- Compared to the resting state, vigorously contracting muscle shows:
a. An increased conversion of pyruvate to lactate.
b. Decreased oxidation of pyruvate to CO2 and water
c. A decreased NADH/NAD+ ratio
d. Decreased concentration of AMP
e. Decreased levels of fructose 2,6-bisphosphate
a. An increased conversion of pyruvate to lactate.
- Muscle glycogen cannot contribute directly to blood glucose levels because:
a. Muscle glycogen cannot be converted to glucose 6-phosphate
b. Muscle lacks glucose 6-phosphatase
c. Muscle contains no glucokinase
d. Muscle contains no glycogen phosphorylase
e. Muscle lacks phosphoglucoisomerase
b. Muscle lacks glucose 6-phosphatase
Which one of the following compounds cannot give rise to the net synthesis of glucose?
a. Lactate
b. Glycerol
c. -Ketoglutarate
d. Oxaloacetate
e. Acetyl CoA
e. Acetyl CoA
- An abnormal, poorly branched glycogen was isolated from the liver of a patient with type IV glycogen storage disease. The deficiency is most probably in:
a. Phosphorylase kinase
b. Glycogen phosphorylase
c. Protein kinase A
d. Amylo--(1,6)-glucosidase
e. Amylo-alpha-(1,4–> alpha-1,6)-transglycosylase
e. Amylo-alpha-(1,4–> alpha-1,6)-transglycosylase
- Liver glycogen can contribute directly to blood glucose levels because:
a. Liver glycogen cannot be converted to glucose 6-phosphate
b. Liver contains glucose 6-phosphatase
c. Liver contains no glucokinase
d. Liver contains no glycogen phosphorylase
e. Liver lacks phosphoglucoisomerase
b. Liver contains glucose 6-phosphatase
- Epinephrine and glucagon would have which of the following effects on glycogen metabolism in the liver:
a. The net synthesis of glycogen is increased
b. Glycogen phosphorylase is activated while glycogen synthase is inactivated
c. Both glycogen phosphorylase and glycogen synthase are activated but at markedly different rates
d. Glycogen phosphorylase is inactivated while glycogen synthase is activated
e. cAMP-dependent protein kinase is activated while phosphorylase kinase is inactivated.
b. Glycogen phosphorylase is activated while glycogen synthase is inactivated
