Lipids Flashcards
Name the three classes of lipids.
Fatty acid derivatives
Hydroxy-methyl-glutaric acid derivatives
Vitamins
How are triacylglycerides formed?
They are formed from a glycerol backbone and three fatty acid molecules. They are a product of esterification reactions.
Give properties of TAG and state where in the body it can be found.
TAG is a hydrophobic molecule which is stored in its anhydrous form in adipose tissue.
What are the products of TAG breakdown and where are they metabolised?
Glycerol –> Liver. Metabolised by glycolysis.
Fatty Acids –> Adipose / Target Tissues. Fatty Acid oxidation releases energy.
What enzyme in the small intestine catalyses breakdown of TAG?
Pancreatic lipase.
What are the two tissues/ cells where Fatty acid oxidation cannot be used to release energy?
Red Blood Cells (these have no mitochondria) and the brain (cannot pass the blood-brain barrier)
Name two hormones which can activate fat mobilisation.
Adrenaline and Glucagon.
Explain why when there is low Extracellular glucose, FA are oxidised.
When glucose is low, there is less substrate for TAG synthesis (glycerol-1-phosphate) being produced from glycolysis, so this leads to an accumulation of FA in the tissues. These are oxidised to release energy.
Why are some fatty acids essential?
Fatty acids with a double bond after C9 cannot be synthesised by the body and therefore they must be sourced from the diet.
Where does activation of fatty acids occur and what is the enzyme responsible for this?
Activation occurs in the cytoplasm.
Fatty acyl coA synthase.
What transporter protein is used to transport activated fatty acids into the mitochondria for B oxidation?
Carnitine shuttle
Name the substance which inhibits the Carnitine shuttle to prevent breakdown of newly synthesised FA.
Malonyl~coA
When a Cn fatty acid enters B oxidation, what is the product?
A C(n-2) molecule and also a C2 which is acetyl~coA and enters the TCA cycle.
What is the enzyme which converts glycerol from TAG breakdown into glycerol phosphate?
Glycerol kinase.
Acetyl~coA is a useful intermediate for anabolism and catabolism. What anabolic processes is it a precursor for?
Hydroxymethylglutaric acid derivatives including Ketone Bodies and Cholestrol.
Fatty Acids
Name three ketone bodies
Acetoacetate, acetone and B hydroxybuturate.
How do statin drugs lower Cholestrol?
Statin drugs lower Cholestrol formation by inhibiting HMG~coA reductase which is a step in the metabolic pathway for Cholestrol synthesis.
How is production of ketone bodies regulated?
Ketone body production is regulated because the starting molecule is acetyl~coA which is diverted from the TCA cycle. When NADH is high this leads to product inhibition, and so acetyl~coA is diverted to alternative pathways.
What is the name of the enzyme which catalyses the reaction from HMG~coA to acetoacetate?
Lyase. This is inhibited when Insulin to Glucagon ratio is high as HMG~coA is used for Cholestrol synthesis. When this ratio is low, lyase is activated and ketone bodies form.
How does muscle protein breakdown provide glucose for the brain?
Protein - amino acids, Pyruvate, gluconeogenesis glucose
In prolonged starvation what fuel molecules do muscles use and why?
Fatty acids and ketone bodies. The prevent usage of glucose which is reserved for the brain.
What is a common condition seen in starvation and also in type one diabetes?
Ketoacidosis. This occurs because acetoacetate and B hydroxybuturate are both relatively strong acids. Ketouria will also be seen because ketone bodies are above the renal threshold.
What happens during fatty acid oxidation if the carbon chain has an odd number of carbons?
In this case, the cycle continues until 3 carbons remain. Carboxylase catalyses carboxylation and the production of methylmalonyl~coA which is then rearrange to succinyl~coA, a Kreb cycle intermediate.
When glucose is low, Pyruvate dehydrogenase is inhibited. How does this help to maintain glucose?
Inhibition of Pyruvate dehydrogenase slows acetyl~coA synthesis, and therefore acetyl~coA –> citrate which I inhibits phosphofructokinase. This leads to a build up of Glucose 6 phosphate which acts as product inhibition on hexokinase and so maintains glucose concentration.
What is glycogen?
Glycogen is a glucose store which is used between meals to maintain glucose plasma concentration.
What is the advantage of the branched structure of glycogen?
It means it can be broken down quickly when required for utilisation.
What is the action of phosphoglycomutase and in which pathway can this be seen?
It converts glucose 6 phosphate to glucose 1 phosphate which can then be utilised to make glycogen in glycogenesis.
Name the two enzymes responsible for adding UDP-glucose to Glycogen.
Glycogen synthase - (a1-4) bonds
Branching enzyme - (a1-6) bonds
When glycogen is broken down, what does it initially form? What enzymes assist in this process?
It forms glucose 1 phosphate. Debranching enzyme and glycogen phosphotase are the two enzymes responsible for this breakdown.
What is the difference between glycogen breakdown in the muscles compared to the liver?
In the muscles, it is converted to glucose 6 phosphate and this enters glycolysis. In the liver the enzyme glucose 6 phosphatase acts on glucose 6 phosphate and converts it back to glucose. This enzyme is not present in muscle.
How is glycogenolysis and glycogenesis regulated?
The rate limiting enzymes are glycogen synthase and glycogen phosphorylase.
Glucagon phosphorylates both of these which inhibits synthase and activates phosphorylase. Insulin has the opposite action.
In muscle stores, glucagon has no effect. In this case what is the activator of glycogen phosphorylase?
AMP which is a low energy signal.
Are lipids soluble or insoluble?
Lipids are insoluble molecules made from C, H and O.
Why do glycogen storage diseases arise and what are the consequences?
They occur due to deficiency or dysfunction of enzymes in glycogen metabolism. Excessive storage leads to tissue damage, whilst low glycogen stores lead to exercise intolerance and hypoglycaemia.
Where does gluconeogenesis occur?
It occurs in the liver and in the kidney cortex.
What are precursors for gluconeogenesis?
Lactate from anaerobic glycolysis, glycerol from TAG breakdown and amino acids (mainly alanine).
Step 10 of glycolysis is irreversible
PEP – Pyruvate. What is the reverse of this in gluconeogenesis?
Pyruvate is converted to oxaloacetate by Pyruvate carboxylase. This is then converted to PEP by PEPCK.
Describe how the action of PEPCK is regulated.
With increase Glucagon/ cortisol there is increased PEPCK and so this reaction is stimulated. With increased insulin, amount decreases and so does reaction rate.
What is the action of fructose1,6, bisphosphotase? How is it regulated with glucagon/ insulin?
This converts fructose 1,6 bis phosphate into fructose 6 phosphate. Glucagon stimulates and increases activity. Insulin inhibits.
Define Hyperplasia
Increase in the number of cells.
Define hypertrophy
Increase in cell size.
What is lipogenesis?
Fatty acid synthesis. Dietary glucose is used as a source of carbon.
What enzyme is involved in lipogenesis?
Fatty acid synthase. It builds them by sequential addition of 2 carbon units provided by malonyl~coA.
What enzyme catalyses the reaction of acetyl~coA to malonyl~coA? How is it regulated?
Acetyl~coA carboxylase.
It is activated by increased insulin or citrate
It is inhibited by glucagon/adrenaline or AMP
