27-01-22 - Metabolic Stores Flashcards
Learning outcomes
- Describe the need for catabolic-anabolic homeostasis in managing the body’s energy requirements
- Explain the interconversion of fuels in the absorptive and postabsorptive state
- Explain the terms: glycogenesis; glycogenolysis; gluconeogenesis
- Describe lipogenesis, lipolysis including beta-oxidation and role in cellular metabolism
- Explain the need for deamination and transamination of amino acids in cellular metabolism
What is metabolism?
What occurs during absorptive/fed states?
What occurs during postabsorptive/fasting states?
What 3 things does insulin promote?
- Metabolism is the mechanisms which couple the demand for energy (which is constant), with the fuel supply (which is intermittent)
- During the absorptive/fed state nutrients are plentiful – fuel broken down and excess stored (anabolism)
- During postabsorptive/fasting states storage molecules are broken down for energy (catabolism) – biosynthesis slows down
• Insulin promotes:
1) Glucose uptake
2) Fatty acid synthesis
3) Protein synthesis
What makes the conversion of storage molecules possible?
What are the 3 effector organs controlling the release of, or interconversion of fuel sources?
What 3 fuel sources can be mobilised?
- Metabolic storage molecules are interconvertible as their pathways are linked by key intermediates
- 3 effector organs controlling the release of, or interconversion of fuel sources:
1) Liver
2) Adipose tissue
3) Muscles
• Fuel sources that can be mobilised:
1) Glucose
2) Triglycerides
3) Amino acids
What is the primary aim of the postabsorptive state?
What 2 processes does blood glucose come from in a postabsorptive state?
Where do these processes occur?
- The primary aim of the postabsorptive state is to maintain blood glucose levels within homeostatic range of 70-110mg/dl or 4-7mmol/L
- Source of blood glucose in postabsorptive state:
1) Glycogenolysis
• Liver glycogen (about 100g) – enough for 3-5 hours of activity, and can be used around the body
• Muscle glycogen – only utilised within the muscle
2) Gluconeogenesis
• Formation of glucose form non-carbohydrate molecules
• Mainly occurs in the liver
• Lipolysis of fatty acids to generate glycerol, which can be converted to glucose
• Catabolism of muscle protein – deamination of amino acids which can be converted to glucose
What is glycogen? Where are the 2 main glycogen reservoirs?
How long can these stores last?
What is glycogen in muscle used for?
How do glycogen stores change?
- Glycogen is a branched polysaccharide storage molecule for glucose
- The 2 main glycogen reservoirs are:
1) Liver
• The liver maintains blood glucose levels, and has enough glycogen for 3-5 hours, or 12 hours overnight fast
2) Skeletal muscle
• Muscle stores glycogen for muscle contraction – channelled into glycolysis (not released into the bloodstream)
• Glycogen stores change constantly with changes in nutritional status
What is glycogenolysis?
What 4 things is it promoted by?
What 2 enzymes are required?
What 2 places does this process occur?
How does it occur in each place?
- Glycogenolysis is glycogen breakdown
- Glycogenolysis is promoted by:
1) Glucagon
2) Adrenalin
3) Cortisol
4) Growth Hormone
• Enzymes needed:
1) Glycogen phosphorylase – α 1,4 linkages
2) Debranching enzyme – α 1,6 linkages
• Glycogenolysis occurs:
1) In the liver
• Glycogen to G-1-P to G-6-P to glucose
• Released into bloodstream (GLUT2) for uptake by all cell, but especially brain and RBCs
2) The muscle
• No G-6-Pase enzyme
• G-6-P enters glycolysis
What is glycogenesis?
What is it promoted by?
How does this process occur?
How are glucose residues formed?
How does branching occur?
- Glycogenesis is the formation of glycogen from sugar
- Glycogenesis is promoted by insulin
- Glucose to G-6-P to G-1-P to Glycogen
- Glucose residues are formed by α 1,4 glycosidic linkages
- Branching occurs via α 1,6 glycosidic linkages
How long od glycogen stores last?
What are lipids?
How much more energy can triglycerides produce than glycogen?
- Glycogen stores last about 3-5 hours
- Lipids are the major form in which energy is stored
- Weight for weight, triglycerides (triacylglycerols) can produce about 6 times as much energy as glycogen
What is gluconeogenesis?
What are 3 examples of substances that can be used in gluconeogenesis?
What are 4 tissues with their primary source of energy being glucose?
Where does gluconeogenesis occur?
Where does it occur in prolonged fasting?
What 3 enzymes are required for gluconeogenesis?
- Gluconeogenesis is the formation of glucose form non carbohydrate sources
- Substances that can be used in gluconeogenesis:
1) Glycerol from triglycerides
2) Glucogenic amino acids (alanine and glutamine)
3) Lactate
• 4 tissues with their primary source of energy being glucose:
1) Brain
2) Red blood cells
3) Renal medulla
4) Lens
- Gluconeogenesis takes place mainly in the liver
- It can also take place in the kidneys in prolonged fasting
• Enzymes required for gluconeogenesis:
1) Pyruvate carboxylase (mitochondria)
2) Phosphoenol pyruvate carboxykinase (mitochondria + cytosol)
3) Glucose-6-Phosphatase (ER)
How is most fat stored?
How are these formed?
How long are fatty acid chains?
What are triglycerides an example of?
- Most fat is stored as triglycerides (triacylglycerols)
- Triglycerides are form when a glycerol molecule undergoes condensation with 3 fatty acids
- The hydrocarbon chains in the fatty acids are usually 14-24 carbon atoms long, with most common FAs being 16 or 18 carbons
- Triglycerides are esters. Which are formed by the reaction of an alcohol and organic acid
Lipid metabolism
What is lipolysis?
What happens to the glycerol and fatty acids produced?
What processes can glycerol and fatty acids then undergo?
- Lipolysis is fat breakdown into glycerol and fatty acids (reverse of lipogenesis)
- The glycerol and fatty acids produced are then released from adipose tissue and metabolised mainly by the liver
1) Glycerol
• Glycerol feeds into gluconeogenesis, but can also be utilised by most cells
• It can be converted into glyceraldehyde-3-phosphate (glycolysis intermediate), which can enter into glycolysis, which results in 15 ATP generated aerobically
2) Fatty acids
• Fatty acids undergo β-oxidation
• They are broken down into Acetic acid (2C) and fused to coenzyme A to form Acetyl CoA
• This process reduces FAD and NAD+, which can then be fe into the ETC
• Acetyl CoA can then enter the citric acid cycle
What needs to happen for ketone bodies to be formed?
What is the limiting factor in the citric acid cycle when glucose is low?
What is converted into ketone bodies?
Where does this occur?
What 3 ketone bodies are formed?
What happens with ketone bodies in diabetes?
- Ketone bodies are formed when carbohydrate intake is inadequate and beta-oxidation product Acetyl CoA is in excess
- When glucose is low, oxaloacetate is the limiting factor in the citric acid cycle, as it is converted to pyruvate on gluconeogenesis
• Acetyl CoA is converted to ketone bodies in the liver:
1) Acetoacetate
2) 3-hydroxybuterate
3) Acetone
- In diabetes, acetoacetate is produced faster than it is metabolised
- This results in ketone bodies accumulating in the blood (potential acidosis) and fruity smell of acetone on the breath
What must happen with excess protein?
What is transamination?
What 2 things can happen to modified keto-acids after transamination?
What is deamination?
What is the difference between a keto acid and ketone body?
- Excess protein cannot be stored, so amino acids are oxidised for energy or converted to fat
- Transamination is the process by which some amino acids can be converted to keto acids e.g amine group transferred to keto-glutamate to from glutamic acid
• These modified keto acids can then:
1) generate pyruvate or keto-acid intermediates for the citric acid cycle
2) be converted to glucose via gluconeogenesis
- Deamination is the removal of an amine group (NH2) prior to oxidation or storage
- A keto acid is an intermediate of the citric acid cycle
- Ketone body is a degradation stage of fatty acid oxidation
What does the hepatic portal vein system ensure?
What are 2 major roles of the liver?
What % of glucose is used by the brain?
What 3 things does resting muscle use as fuel?
What % of glycogen reserves is located in muscles?
- The hepatic portal vein system ensures the liver has ready access to absorbed nutrients
- The liver is the major metabolism centre orchestrating interconversion of CHO, proteins, fats and lactate
- It also maintains blood glucose levels
- 60% of glucose is used by the brain in a day (about 120g a day) as it has no stores of glycogen or glucose
• For fuel, resting muscle uses:
1) Fatty acids
2) Glucose
3) Ketone bodies
• Muscles make up about ¾ of the body’s stores of glycogen
