Energy storage Flashcards
What is the bodies preferred fuel?
Glucose
What is the result of glucose being the bodies preferred food source?
The body requires a constant level of glucose as an energy source
Which tissues have an absolute requirement for glucose as energy source?
- Erythrocytes (RBCs) and leukocytes
- Testes
- Kidney medulla
- Lens and cornea of eye
Why is a stable glucose level required for normal brain function?
Because the brain prefers to use glucose as a fuel
Can the brain use any source other than glucose for fuel?
Yes, it can use ketone bodies, but not immediately
How long does it take for the brain to be able to utilise ketone bodies?
Oct-14
How much of the brains energy requirement can be obtained from ketone bodies?
~50%
What is required to enable blood glucose to be kept at required levels?
Store of glycogen
What form is glycogen stored in?
Granules
What cells have glycogen stores?
All of them to an extent
How is muscle glycogen present?
As both intra- and intermyofibrillar glycogen granules
How is liver glycogen stored?
As granules within hepatocytes
Describe the structure of glycogen
- Polymer consisting of chains of glucose residues
- Chains organised in branches
- Residues linked by α-1,4- glycosidic bonds, with α-1,6-glycosidic bonds forming at branch points
Where to the branches in glycogen originate from?
A dimer of the protein glycogenin
What does the protein glycogenin act as in glycogen?
A primer at core of glycogen structure
How often are the branch points in glycogen?
Every 8-10 residues
What is the name given to glycogen synthesis?
Glycogenesis
Give the reactions that lead to the conversion of glucose to glycogen
- Glucose + ATP → glucose 6-phosphate + ADP
- Glucose 6-phosphate ↔ glucose 1-phosphate
- Glucose 1-phosphate + UTP + H 2 O→ UDP-glucose + 2Pi
- Glycogen (n resides) + UDP-glucose→ glycogen (n+1 residues) +UDP
What enzyme is required for conversion of glucose to G-6-P?
Hexokinase
What is hexokinase called in the liver?
Glucokinase
What is the enzyme for the conversion of G-6-P to G-1-P?
Phosphoglucomutase
What is the enzyme for the addition of glycogen residues (in reaction 4)?
NAME?
What does glycogen synthase do?
Adds α-1,4-glycosidic bonds
What does branching enzyme do?
Adds α-1,6-glycosidic bonds
What is the name given to glycogen degredation?
Glycogenolysis
Give the equations for glycogenolysis
- Glycogen (n residues) + Pi → G-1-P + glycogen (n-1 residues)
- G-1-P ↔ G-6-P
What is the enzyme used for removal of glycogen residues?
- Glycogen phosphorylase
- or de-branching enzyme
What happens to G-6-P in muscle?
Glycolysis
What is happening when the muscle performs glycolysis on the G-6-P released from glycogen?
It is being used for local energy production
What happens to G-6-P in the liver?
Converted to glucose
What happens to the glucose produced from glycogen by the liver?
It is released into the blood for use by other body tissues
Is glycogenolysis just reversal of glycogenesis?
No
What is the result of glycogenolysis not being a simple reversal of glycogenesis?
Different enzymes allow for simultaneous inhibition of one pathway and stimulation of the other
Other than glycogenolysis, what other method does the liver have of producing G-6-P?
Gluconeogenesis
What is liver glycogen a buffer for?
Blood glucose concentration
How much of the liver mass is glycogen?
10%
What happens to the glucose in muscle?
It enters glycolysis, either being oxidised to CO 2 + ATP, or converted into lactate
What enzyme does the muscle lack?
G-6-Pase
What is the rate limiting enzyme in glycogen synthesis in the liver?
Glycogen synthase
What is the rate limiting enzyme in glycogen degradation?
Glycogen phosphorylase
In what fashion does glycogen metabolism regulation occur?
Reciprocal
What hormones regulate liver glycogen metabolism?
- Glucagon
- Adrenaline
- Insulin
What effect does glucagon and adrenaline have on glycogen synthase?
Decreases enzyme activity
What effect does glucagon and adrenaline have on glycogen phosphorylase?
Increases enzyme activity
By what mechanism do adrenaline and glucagon affect the activity of enzymes?
Phosphorylation
What effect does insulin have on glycogen synthase?
Increases enzyme activity
What effect does insulin have on glycogen phosphorylase?
Decreases enzyme activity
By what mechanism does insulin affect the activity of enzymes?
De-phosphorylation
In what way does regulation of muscle glycogen differ from liver glycogen?
- Glucagon has no effect
- AMP acts as an allosteric activator of muscle glycogen phosphorylase, but not liver form of enzyme
What are glycogen storage diseases?
Inborn errors in metabolism
What do glycogen storage diseases arise from?
Deficiency or dysfunction of enzymes of glycogen metabolism
How many distinct glycogen storage diseases are there?
11
What does the severity of a glycogen storage disease depend on?
The enzyme/tissue affected
What tissues can be affected by glycogen storage diseases?
Liver and/or muscle
How can someone have a disease in the liver or the muscle, but not both?
Glycogen phosphorylase is coded for by a different gene in liver than in the muscle, so it can be mutated in one but not the other
What can excess glycogen storage lead too?
Tissue damage
What can diminished glycogen stores lead to?
Hypoglycaemia and poor exercise tolerance
Give two examples of glycogen storage diseases
- von Gierkes disease
- McArdles disease
What causes von Gierkes disease?
Glucose-6-phosphate deficiency
What causes McArdles disease?
Muscle glycogen phosphate deficiency
What is gluconeogenesis?
The production of new glucose not pre-exisiting stores in glycogen
When do we need to be able to synthesise new glucose?
When glycogen stores are low
What happens beyond ~8 hours fasting?
Liver glycogen stores start to deplete
Where does gluconeogenesis occur?
In liver, and to a lesser extent kidney cortex
How many major precursors for gluconeogenesis are there?
3
What are the 3 major precursors for gluconeogenesis?
- Lactate
- Glycerol
- Amino acids
When is lactate produced?
In anaerobic glycolysis in exercising muscles and RBC’s
How does the process of gluconeogenesis using lactate occur?
Using the Cori Cycle
What happens in the Cori cycle?
- In the liver, 2 lactate molecules are converted to glucose
- Glucose is transported from liver to muscle in the blood
- In the muscle, glucose is converted into two lactate
- The lactate produced in the muscle is transported in the blood to the liver
When is glycerol released?
From adipose tissue when triglycerides are broken down
What amino acids are used for gluconeogenesis?
Mainly alanine
Can acetyl~CoA be converted into pyruvate?
No
Why can’t acetyl~CoA be converted into pyruvate?
Because the pyruvate dehydrogenase reaction is irreversible
What is the result of the inability of acetyl~CoA to be converted into pyruvate?
There is no net synthesis of glucose from acetyl~CoA
How many reactions in gluconeogenesis are not simple reversions of corresponding steps in glycolysis?
3
What are the key enzymes in gluconeogenesis?
- Phosphoenolpyruvate carboxykinase (PEPCK)
- Fructose 1,6-bisphosphatease
- Glucose 6-phosphatease
Which of the key enzymes in gluconeogenesis are key sites of control for the pathway?
- Phosphoenolpyruvate carboxykinase (PEPCK)
- Fructose 1,6-bisphosphatease
What does PEPCK do?
Catalyses conversion of oxaloacetate to phosphoenolpyruvate
What does fructose 1,6-bisphosphatease do?
Catalyses conversion of fructose 1,6-bisphosphate to fructose 6-phosphate
What are the 2 key control enzymes in gluconeogenesis controlled by?
Hormones
What are the 2 key control enzymes in gluconeogenesis controlled in response to?
- Starvation
- Prolonged exercise
- Stress
What hormones affect the action of the key control enzymes in gluconeogenesis?
- Glucagon
- Cortisol
- Insulin
What affect does glucagon and cortisol have on PEPCK?
Increases the amount
What effect does glucagon and cortisol have on fructose 1,6-bisphosphate?
Increased amount and activity
What is the overall effect of glucagon and cortisol on gluconeogenesis?
Stimulates
What effect does insulin have on PEPCK?
Decreases amount
What effect does insulin have on fructose 1,6-bisphosphate?
It decreases the amount and activity
What is the overall effect of insulin on gluconeogenesis?
Inhibits
How are lipids stored?
As triacylglycerols (TAGs)
What happens when energy intake is in excess of requirements?
It’s converted to triacylglycerol for storage
Are TAGs hydrophilic or hydrophobic?
Hydrophobic
How must TAGs be stored due to them being hydrophobic?
In anhydrous form in specialised tissue
What is the specialised storage tissue for TAGs?
Adipose tissue
Is TAG an efficient energy store?
Yes, highly
How does the energy content per gram differ in TAGs and carbohydrate/protein?
x2 more in TAG than in carbohydrate or protein
Under what conditions are TAG’s utilised?
NAME?
How is storage and metabolism of TAGs controlled?
Hormones
Describe the structure of adipocytes
A large lipid droplet with cytoplasm and organelles pushed to edge
What does the lipid droplet in adipocytes consist of?
Mainly TAG and cholesterol ester
How big are adipocytes?
~0.1mm in diameter, but expand as more fat is added
How much can adipocytes increase in size on weight gain?
About fourfold
What happens once adipocytes can’t expand anymore on weight gain?
They divide, increasing the total no. of fat cells
What is fatty acid synthesis called?
Lipogenesis
Where does lipogenesis occur?
Mainly in liver
What is the major source of carbon for lipogenesis?
Dietary glucose
How are fatty acids produced from glucose?
- Glucose is converted to pyruvate in the cytoplasm
- Pyruvate enters mitochondria, forms acetyl~CoA and OAA
- Acetyl~CoA and OAA condenses to form citrate
- Citrate goes back to cytoplasm, and is cleaved back to acetyl~CoA and OAA
- Acetyl~CoA carboxylase produces malonyl~CoA from acetyl~CoA
- Fatty acid synthase complex builds up fatty acids by sequential addition of 2 carbon units provided by malonyl~CoA
What is the key regulator in fatty acid synthesis?
Acetyl~CoA carboxylase
What does the fatty acid synthesis process require?
Both ATP and NADPH
What increases fatty acid synthesis?
- Insulin
- Citrate
By what mechanism does insulin increase fatty acid synthesis?
Covalent de-phosphorylation
By what mechanism does citrate increase fatty acid synthesis?
Allosteric activation
What decreases fatty acid synthesis?
Glucagon/adrenaline and AMP
By what mechanism do glucagon and adrenaline decrease fatty acid synthesis?
Covalent phosphorylation
By what mechanism does AMP decrease fatty acid synthesis?
Allosteric inhibition
What is the difference in the purpose cycle of reactions between FA oxidation and FA synthesis
- In FA oxidation, the cycle of reactions remove C 2
- In FA synthesis, the cycle of reactions add C 2
What is the difference in how is the C 2 is transferred in FA oxidation and FA synthesis?
- In FA oxidation, C 2 removed as acetyl~CoA
- In FA synthesis, C 2 added as acetyl~CoA
Which of FA oxidation or FA synthesis produced acetyl~CoA, and which consumes it?
NAME?
What is the difference in the site of FA oxidation and FA synthesis?
- Oxidation occurs in mitochondria
- Synthesis occurs in cytoplasm
What is the difference in the enzymes used in FA oxidation and synthesis?
NAME?
Is FA synthesis oxidative or reductive?
Reductive
What is the result of FA synthesis being reductive?
It requires NADPH
What is the difference in ATP requirement between FA oxidation and synthesis?
NAME?
What is the difference in what the intermediates are linked to in FA oxidation and synthesis?
NAME?
What is the difference in regulation between FA oxidation and synthesis?
- Oxidation is regulated indirectly by availability of fatty acids in mitochondria
- Synthesis is regulated directly by activity of acetyl~CoA carboxylase
What is the difference in reaction to glucagon and adrenaline between FA oxidation and synthesis?
NAME?
What is the difference in reaction to insulin between FA oxidation and synthesis?
NAME?
What is the process of fat mobilisation called?
Lipolysis
Give the equation for lipolysis
Triacylglycerol (in adipose tissue) → glycerol (in blood) + free fatty acids
What enzyme catalyses lipolysis?
Hormone sensitive lipase
What hormones is hormone sensitive lipase regulated by?
NAME?
What is the effect of glucagon and adrenaline on hormone sensitive lipase?
Stimulates
By what mechanism does glucagon and adrenaline stimulate hormone sensitive lipase?
Phosphorylation
What is the effect of insulin on hormone sensitive lipase?
Inhibited
By what mechanism does insulin inhibit hormone sensitive lipase?
Dephosphorylation
Where does the glycerol in the blood produced by lipolysis go?
To liver
What happens to glycerol in the liver?
It’s utilised as a carbon source for gluconeogenesis
How do free fatty acids travel in the blood?
Complexed with albumin
Where do free fatty acids in the blood go?
Muscle and other tissues
What happens to free fatty acids in the muscle and other tissues?
ß-oxidation
