2.1 Energy Storage Flashcards
What is the preferred energy storage in the body?
Glucose as some tissues have an absolute
requirement for glucose as an energy source
What tissues have an absolute requirement for glucose?
Red blood cells
Neutrophils
Innermost cells of the kidney medulla
Lens of the eye
Why is a store of glucose required?
To maintain a stable blood glucose level between meals
What is the normal range of blood sugar levels?
3.0 to 5.5 mol/L
What is hypoglycaemia?
Low blood sugar. Caused by diabetes, acute alcohol poisoning, intense exercise. Symptoms include confusion, weakness, nausea, muscle cramps, brain damage.
How is glucose stored?
As glycogen
How is glycogen stored?
Glycogen is very large and stored in granules in liver and skeletal muscle.
Why is it beneficial to store glucose as glycogen rather than as molecular glucose?
Large size of glycogen molecule means that many glucose molecules can be stored with minimal osmotic effect in the storage tissues. So less water brought into the cell than if glucose was not stored.
How is glycogen stored in muscle?
About 300g is stored in muscle. Stored as intra and intermyofibrillar glycogen.
How is glycogen stored in the liver?
100g of glycogen stored as granules in hepatocytes
What the of bonding is present in glycogen molecules?
α-1-6 Glycosidic bonds form branch points
α-1-4 Glycosidic bonds join chains
Why is it beneficial for glycogen to be a highly branched structure?
Enzymes can react at many different sites to release glucose quickly
Glucose residues can be swiftly added.
What is glycogenin?
A protein that is at the centre of glycogen molecules. Acts as a primer at core of glycogen structure
What is glycogenesis?
Glycogen synthesis
Describe the 4 steps in synthesis of glycogen
- Glucose and ATP are converted to glucose 6-phosphate and ADP by hexokinase
- Glucose-6-phosphate is converted to glucose-1-phosphate by phosphoglucomutase
- Glucose-1-phosphate + UTP + H2O is catalysed with G1P Uridyltransferase to form UDP glucose and PPi
- UDP-glucose can be added to glycogen branches by glycogen synthase or branching enzymes.
Synthesis of glycogen requires energy at stage 1 and 3
What is glycogenolysis?
Glycogen degeneration, not a reversal of glycogenesis.
Where does glycogenolysis occur?
- Skeletal muscle in response to exercise.
2. Liver when fasting or stress response.
What enzymes are used in glycogenolysis?
Glycogen phosphorylase = breaks alpha 1-4 glycosidic bonds
Debranching enzyme = breaks alpha 1-6 glycosidic bonds.
What are the 2 steps in glycogenolysis?
- 1-4 bonds : Glycogen + Pi phosphorylated to glucose-1-phosphate + glycogen(-1 residues) by glycogen phosphorylase
1-6 bonds : glycogen + Pi is phosphorylated by debranching enzyme to glucose + glycogen (-1 residues) - Glucose-1-phosphate can be transformed into glucose 6 phosphate by phosphoglucomutase.
Why do glycogen stores serve different functions in liver and muscle?
In liver, glucose-6-phosphate is converted to glucose by glucose-6-phosphatase and exported in blood for use in other tissues. Liver glycogen is a buffer of blood glucose levels.
In muscle glucose-6-phosphate enters glycolysis for energy production. Muscle lacks the enzyme glucose-6-phosphatase. Energy is used by muscle cells.
What stimulates glycogen phosphorylase?
In liver, glycogen phosphorylase is stimulated by adrenaline and glycogon
In muscle tissue, glycogen phosphorylase is stimulated by AMP and adrenaline.
What enzymes are needed to convert glucose to glucose-6-phosphate?
Hexokinase in most cells.
Glucokinase in liver.
What enzymes are needed to form glycogen from glycose-1-phosphate?
Glucose-1-phosphate uridyltransferase
Glycogen synthase
Branching enzyme
How is liver glycogen metabolism regulated?
Regulated by controlling activities of enzymes catalysing irreversible reactions.
Glycogenesis = rate inviting enzyme glycogen synthase Glycogenolysis = glycogen phosphorylase.
How are the rate limiting enzymes of glycogen metabolism in the liver controlled?
- Glycogen synthase
- inhibited by glucagon and adrenaline.
- inhibited by phosphorylation
- stimulated by insulin. - Glycogen phosphorylase
- stimulated by glucagon and adrenalin
- inhibited by insulin
How does mobilisation of glycogen stores vary from mobilisation of liver glycogen stores?
Muscle glycogen stores differ in that Glucagon has no effect as no receptors for glucagon there.
Also AMP is an allosteric activator of muscle glycogen phosphorylase but not of the liver form of enzyme
What are glycogen storage diseases?
Inborn errors of metabolism (inherited diseases)
Arise from deficiency or dysfunction of enzymes of glycogen metabolism
12 distinct types.
Incidence varies ~1 in 20,000 – ~1 in 100,000.
Severity depends on enzyme/tissue affected
What symptoms can a patient with a glycogen storage disease have?
Liver and /or muscle can be affected
Excess glycogen storage can lead to tissue damage
Diminished glycogen stores can lead to hypoglycaemia & poor exercise tolerance
Glycogen structure may be abnormal
Give 2 examples of a glycogen storage disease
von Gierke’s disease - glucose 6-phosphatase (only present in liver) deficiency
McArdle disease - muscle glycogen phosphorylase deficiency
What is gluconeogenesis?
The production of new glucose
When does gluconeogenesis occur?
Beyond ~ 8 hours of fasting, liver glycogen stores start to deplete and an alternative source of glucose is required
Where does gluconeogenesis occur?
Occurs in Liver and to lesser extent in Kidney cortex
What are 4 major precursors for gluconeogenesis?
Lactate - From anaerobic glycolysis in exercising muscle and red blood cells (Cori cycle) Glycerol - Released from adipose tissue breakdown of triglycerides. Amino acids - Mainly alanine. Pyruvate - metabolite in glycolysis
Why is there no net synthesis of glucose from Acetyl-CoA?
As acetyl-CoA cannot be converted into pyruvate (pyruvate dehydrogenase enzyme is irreversible)
What are the three key enzymes in gluconeogenesis?
1 . Phosphoenolpyruvate carboxykinase (PEPCK) (stimulates oxaloacetate to Phosphoenolpyruvate)
- Fructose 1,6-biphosphatase (fructose 1,6-bisphosphate to fructose 6 phosphate)
- Glucose-6-phosphatase (glucose-6-phosphate to glucose)
How are 2 key enzymes of gluconeogenesis controlled?
- Phosphoenolpyruvate carboxykinase (PEPCK)
- activity increased by glucagon and cortisol
- activity decreased by insulin - Fructose 1,6-biphosphatase
- activity and amount increased by glucagon
- activity and amount decreased by insulin.
Both regulated by hormones in response to starvation/fasting, prolonged exercise, stress
What is the tie course of glucose utilisation from feeding to 10 hours?
Glucose from food for 2 hours after feeding
Glycogenolysis up to 8-10 hours
Gluconeogenesis 8-10 hours onwards
How is energy intake in excess of requirements stored?
By conversion to triacylglycerols and stored in bulk in anhydrous adipose tissue.
Why are triacylglycerols stored in adipose tissue?
As TAG’s are hydrophobic.
When are lipid stores utilised?
Utilised in prolonged aerobic exercise, stress, starvation, during pregnancy
How is the storage and mobilisation of TAGs controlled?
Hormonal control
- storage promoted by insulin
- mobilisation promoted by glucagon, adrenalin, cortisol, growth hormone, thyroxine.
What is an adipocyte and describe its structure.
A specialised cell type for storage of TAGs. Appears as a large lipid droplet (mainly TAG and cholesterol ester) with cytoplasm and organelles pushed to the edge.
Typical adipocyte ~0.1mm in diameter. Cells expand as more fat
added and split into 2 when they get too big. Hypertrophy before hyperplasia.
Roughly 15kg of adipocytes in average man
What occurs to ingested fats in the small intestine?
They are broken down by pancreatic lipase into fatty acids and glycerol which can then be absorbed into the intestinal epithelial cell.
What occurs to fatty acids and glycerol after they have been absorbed by the intestinal epithelial cell?
Glycerol and fatty acids reform TAGs which is then packaged into lipoproteins to form a chylomicron. Chylomicrons can then exit the intestinal epithelial cell in the lymphatic system
What is lipogenesis?
Fatty acid synthesis by acetyl-CoA at the expense of ATP and NADPH.
Where does lipogenesis occur?
In the liver.
Describe how citrate enters liver cells.
- Glucose is metabolised to pyruvate in cytoplasm of liver cells (glycolysis).
- Pyruvate enters mitochondria and forms acetyl-CoA & oxaloacylacetate (OAA) which then condense to form citrate
- Citrate enters the cytoplasm of the liver cells from the mitochondria
How is malonyl-CoA produced in liver cells?
Citrate is cleaved back to acetyl-CoA and oxaloacylacetate. Acetyl-CoA carboxylate produces malonyl-CoA from acetyl-CoA.
What is the function of the fatty acid synthase complex?
Fatty acid synthase complex builds fatty acids by
sequential addition of 2 carbon units provided by malonyl-CoA.
What is the function of malonyl-CoA?
Malonyl-CoA is a 3 carbon compound that donates 2 carbon atoms to the growing fatty acid chain with the loss of CO2.
Why is the pentose phosphate pathway essential for lipogenesis?
As the pentose phosphate pathway produces NADPH which is essential for the function of the fatty acid synthase complex.
What is the key regulatory enzyme in liver lipogenesis?
Acetyl-CoA carboxylase (produces malonyl-CoA)
What enzymes regulate acetyl-CoA carboxylase?
Insulin and citrate stimulate activity
Glucagon, adrenaline and AMP decrease activity
What components contribute towards forming TAGs in the liver?
Fatty acids formed by the fatty acid synthase complex and glycerol-3-phosphate from glycolysis
What lipoprotein moves lipids synthesised in the liver?
Very low density lipoprotein
Why does catabolic and anabolic pathways occur via different routes?
Allows greater flexibility
Better control
Thermodynamically irreversible steps can be by-passed.
Where does fatty acid oxidation occur?
Mitochondria
What is lypolysis?
Mobilisation of stored fat
What is the first step in lypolysis?
The first step is the breakdown of stored TAGs in adipose tissue into glycerol and free fatty acids. Hormone sensitive lipase catabolises this reaction.
What hormones regulate or one sensitive lipase in adipose tissue?
Activated by glucagon and adrenaline
Inhibited by insulin
After lipolysis, what is the function of glycerol?
Travels to liver and utilised as carbon source for gluconeogenesis
After lypolysis, what is the function of free fatty acids?
Free fatty acids travel complexed with albumin to muscle and other tissues. Is broken down to release acetyl-CoA via Beta oxidation
In obese people, how are energy stores affected?
Triacylglycerol stores increase.
