Energy Production- Lipids Flashcards
Are lipids structurally similar or diverse?
Diverse
Are lipids generally hydrophilic or hydrophobic?
Hydrophobic
What is the result of lipids generally being hydrophobic?
They’re generally insoluble in water
What elements to most lipids contain?
C, H and O only
What elements do some lipids contain?
Phospholipids contain P and N
Are lipids more or less reduced than carbohydrates?
More
What is the result of lipids being more reduced than carbohydrates?
NAME?
What are the 3 classes of lipids?
- Fatty acid derivatives
- Hydroxy-methyl-glutaric acid derivates
- Vitamins
What are the 4 types of fatty acid derivatives?
NAME?
What are fatty acids used for?
Fuel molecules
What are triglycerides used for?
NAME?
What are phospholipids used for?
Components of membranes and plasma lipoproteins
What are eicosanoids used for?
Local mediators
What do local mediators do?
Signal between cells
What is the advantage of having local mediators?
They produce a coordinated response
What are the 4 types of hydroxy-methyl-glutatic acid derivatives?
NAME?
What are ketone bodies?
Water soluble fuel molecules
What are ketone bodies derived from?
Fats
What is cholesterol used for?
- Membranes
- Steroid hormone synthesis
What are cholesterol esters used for?
Cholesterol storage
What are bile acids and salts used for?
Lipid digestion
Can the body make vitamins?
No
What are triacylglycerols (TAGs) composed of?
- Glycerol backbone
- Fatty acid side chain
What is the glycerol backbone in TAGs?
3C sugar derived from glycolysis
What does the fact that the glycerol backbone comes from glycolysis mean?
Fatty acid synthesis requires glycolysis
Why is it said that the fatty acid side chains are highly reduced?
There are 2 H’s on every atom
What is the process of producing TAGs from glycerol and fatty acids called?
Esterification
What is the process of producing glycerol and fatty acids from TAGs called?
Lipolysis
What must be done due to the fact that TAGs are hydrophobic?
They must be stored in anhydrous form
What tissues are TAGs stored in?
Specialised tissue- adipose
When are TAGs utilised?
NAME?
How is storage and mobilisation of TAGs controlled?
Hormones
What are triglycerides broken down to in the GI tract?
NAME?
Can glycerol and fatty acids be transported in the blood?
- Glycerol can
- Fatty acids can’t
How are fatty acids transported in the blood?
On chylomicrons
Where does glycerol end up?
Liver
Where do chylomicrons take fatty acids?
Adipose tissue
What happens when the muscles demand fuel?
Adipose is broken down to release fatty acids, which are carried in the blood to muscles
Where does stage 1 of dietary triacylglycerol metabolism occur?
In the GI tract- extracellular
What does stage 1 of dietary TAG metabolism occur due to?
Lipases
What releases the lipases responsible for stage 1 of TAG metabolism?
Pancreas
What do the lipases do in stage 1 of TAG metabolism?
Hydrolyse lipids in the small intestine into fatty acids and glycerol
What happens once the lipids have been hydrolysed in the small intestine?
They are recombined in the small intestine and transported as TAG by lipoproteins (chylomicrons)
Where do chylomicrons transport TAG’s to?
Adipose tissue and consumer tissue
What happens to TAGs in adipose tissue?
It is stored as TAG until fat mobilisation
What stimulates fat mobilisation?
Glucagon / adrenaline
What inhibits fat mobilisation?
Insulin
What enzyme is responsible for fat mobilisation?
Hormone-sensitive lipase
What carries mobilised fat from adipose tissue to consumer tissues?
FA-albumin
Why is FA-albumin needed to carry mobilised fat?
Because fat is insoluble, therefore can’t go around on it’s own
What happens to fats at consumer tissues?
Fatty acids are oxidised to produce energy
Where can fatty acid oxidation not occur?
- Tissues without mitochondria, e.g. RBCs
- Brain
Why can’t fatty acids be oxidised to produce energy in tissues without mitochondria?
They are highly reduced, so produce lots of reducing equivalents, which needs mitochondria
Why can’t fatty acids be oxidised to produce energy in the brain?
Fatty acids don’t easily pass through the blood-brain barrier
What happens to fatty acids in the GI tract?
They are converted back to triglycerides
How are fatty acids packaged?
Into lipoprotein particles- chylomicrons
How are packaged fatty acids released into circulation?
Via lymphatics
What does low extracellular [glucose] result in?
Fatty acid release as an alternative fuel
Why does low extracellular [glucose] lead to fatty acid release as an alternative fuel?
If [glucose] falls, [glycerol-1-P] also falls, so substrate not available for resynthesis, leading to fatty acid build up
What is the general formula of fatty acids?
CH 3 (CH 2 ) n COOH where n=14-18
Are fatty acids saturated or unsaturated?
Can be either
What is meant by fatty acids being amphipathic?
They contain both hydrophilic and hydrophobic groups
Why are certain polyunsaturated fatty acids essential?
Mammals cannot introduce a double bond beyond C9
Where does stage 2 of FA metabolism occur?
Mitochondria
Where is the FA activated?
Outside of mitochondrion, in the cytoplasm
How is a FA activated?
By linking of CoA, via a high energy bond
What enzyme is used to activate FA’s?
Fatty acid CoA synthase
Give the equation for the activation of fatty acids
Fatty acid + ATP + CoA → fatty acid~CoA + AMP +2Pi
What is 2Pi
Pyruphosphate- 2 phosphates together
Is 2Pi stable or unstable?
Very unstable
What is the result of 2Pi being very unstable?
It hydrolyses spontaneously, pushing the reaction in the forward direction
How are activated fatty acids transported across inner mitochondrial membrane?
Using carnitine shuttle
What happens to FA during stage 2 of FA metabolism?
They cycle through a sequence of oxidative reactions, with C 2 removed each cycle
Give the equation for the reaction that occurs at each cycle of stage 2 of FA metabolism?
C n + FAD + H 2 O + NAD + → C n-2 + C 2 + FADH 2 + NADH + H +
What does the carnitine shuttle do?
Transports fatty acyl~CoA across the mitochondrial membrane
How does the carnitine shuttle work?
- In the intermembrane space, carnitine is converted to acyl carnitine by action of the enzyme of CAT1. This reaction also converts acyl~CoA to CoA
- The acyl carnitine can be transported through the inner mitochondrial membrane by the carnitine shuttle transporter
- In the matrix, acyl carnitine is converted to carnitine by the action of CAT2. This reaction also converts CoA to acyl~CoA- there is now acyl~CoA inside the matrix .
- The carnitine produced can be transported back out to the intermembrane space by the carnitine shuttle transporter
What is the result of the carnitine shuttle be regulated?
It controls the rate of FA oxidation
What inhibits the carnitine shuttle?
Malonyl~CoA
What is malonyl~CoA?
Short, activated fatty acid that is a precursor to fat biosynthesis
What can happen if there are defects in the transport system?
Won’t be able to switch to fatty acid metabolism, because can’t get across mitochondrial membrane
What are the symptoms of defects in the carnitine transport system?
NAME?
What is fatty acid catabolism also known as?
ß-oxidation
Give the equation for ß-oxidation
C n + FAD + H 2 O + NAD + + CoA→ C n-2 + acetyl~CoA + FADH 2 + NADH + H +
What are all intermediates linked to in ß-oxidation?
CoA
Is more energy derived from glucose or FA metabolism?
FA
Where is glycerol metabolised?
In the liver
How does glycerol get to the liver?
It is transported in the blood
Describe the metabolism of glycerol
- Glycerol converted to glycerol phosphate by the action of glycerol kinase. This requires ATP
- Glycerol phosphate can be used in triacylglycerol synthesis, or converted into DHAP (which also converts NAD + to NADH)
- DHAP can then be used in glycolysis
What is the main convergence point for catabolic pathways?
Acetyl-CoA
What does acetyl-CoA consist of?
CH 3 CO group linked to CoA
How is theCH 3 CO group linked to CoA?
Via a S atom
What is the significance of acetyl-CoA being linked by a S atom?
High energy of hydrolysis, therefore is an energy storing bond
What vitamin does CoA contain?
B
What is the significance of CoA containing vit B?
The body can’t produce it
What is the function of acetyl~CoA?
It’s an important intermediate in both catabolic and anabolic pathways
What can acetyl~CoA be converted into?
- Fatty acids
- CO 2
- Hydroxymethylglutaric acid (HMG)
What can fatty acids be converted into?
NAME?
What can HMG be converted into?
NAME?
How many ketone bodies are produced in the body?
3
What are the 3 ketone bodies produced in the body?
NAME?
Effectively, what is acetoacetate?
2 acetate molecules linked together
Where is acetoacetate found?
Liver
What produces acetone?
Spontaneous (non-enzymatic) decarboxylation of acetoacetate
Where is ß-hydroxybutayrate found?
In the liver
What is the normal plasma ketone body concentration?
What is it called when a patient has a plasma ketone concentration of 2-10mM?
Physiological ketosis
When may physiological ketosis occur?
Starvation conditions
What is it called when a patient has a plasma ketone concentration of >10mM?
Pathological ketosis
When may pathological ketosis occur?
Untreated type 2 diabetes
What synthesises ketone bodies?
Liver mitochondria
Describe the synthesis of ketone bodies
- Acetyl~CoA converted into HMG~CoA by action of synthase
- HMG~CoA can be converted into mevalonate by action of HMG-CoA reducatase (which is consequently converted into cholesterol), or acetoacetate by action of lyase.
- Acetoacetate converted to acetone by spontaneous breakdown, or ß-hydroxybutyrate
How can HMG-CoA be used as a site of action clinically?
For statin drugs- if inhibited, it can reduced cholesterol levels in patients
How is ketone body production controlled in the liver?
The acetyl-CoA can be diverted into the TCA cycle, which reduces substrate availability for ketone body production
What enzymes are involved in the regulation of ketone body production in the liver?
- Isocitrate dehydrogenase
- α-ketoglutarate dehydrogenase
How does isocitrate dehydrogenase and α-ketoglutarate dehydrogenase regulate ketone body production in the liver?
- These enzymes are inhibited by low NAD + substrate availability and NADH product inhibition.
- If they are inhibited, build up of product, meaning less acetyl-CoA diverted into TCA cycle, so more ketone body production
Describe the metabolism of ketone bodies
- Acetoacetate and ß-hydroxybutyrate in the liver can be transported in the blood to the muscle
- In the muscle,ß-hydroxybutyrate is converted into acetoacetate (which also causes conversion of NAD + to NADH)
- Acetoacetate + succinyl CoA (in the TCA) → acetoacetate~CoA+ succinate (in the TCA) - this reaction keeps the TCA cycle going, which produces ATP
- The acetoacetate~CoA is converted into acetyl~CoA, which feeds into the TCA cycle at citrate
What happens when acetoacetate is carried in the blood?
Some is lost as acetate in the bloodstream
What happens when ß-hydroxybutyrateis carried in the blood?
Italso carries hydrogen
What hormone ratio regulates ketone body synthesis?
Insulin:glucagon
In what insulin:glucagon ratio are ketone bodies synthesised?
When insulin is low, therefore glucagon is high
In what conditions would insulin be low and glucagon high?
NAME?
What happens when insulin is high and glucagon is low?
Lyase (the enzyme that produces ketone bodies is inhibited), and reductase is activated, leading to cholesterol synthesis
What is the advantage of ketone bodies in starvation conditions?
They spare glucose
Why is advantageous for ketone bodies to spare glucose?
The body needs to maintain circulating glucose to supply the brain, RBC etc
Are ketone bodies hydrophilic or hydrophobic?
Hydrophilic
What happens when ketone bodies rise above the renal threshold?
They are excreted in urine
What is it called when ketone bodies are excreted in urine?
Ketouria
What condition occurs when ketone body concentrations get to high?
Ketoacidosis
What is ketoacidosis?
Acidification of the circulation
Why does ketoacidosis occur?
Because acetoacetate and ß-hydroxybutyrate are relatively strong organic acids
Why can ketoacidosis sometimes be detected on the breath?
Because the volatile acetone may be excreted via the lungs
