Fat Metabolism Flashcards
What are the main features of lipids
- Hydrophobic
- Heterogenous group
- Show greater structural variation than other biological macromolecules
- Not polymeric BUT can aggragate
What are the 3 main functions of lipids
- Bilayer (aiding the partitioning of cellular contents)
- Energy stores
- intra- and inter-cellular signaling
How are lipids transported due to their insoluble nature
Lipids are found compartmentalised or transported in association with protein
e.g. lipoprotein particles
There are several major classes of lipid, one of which being Fatty Acids (carboxylic acid)
A substantial amount of free fatty acids can be found in the plasma, what are their uses in the cell?
- Fatty acids are oxidised by tissue (e.g. liver & muscle) for energy
- Components of membrane lipids (e.g. phospholipids & glycolipids)
- Can be linked to intra-cellular proteins to enhance membrane-association
What is the chemistry behind triacylglycerols
Triacylglycerols are esterified to glycerol (via their carboxyl group)
Why are triacylglycerols biologically important
- As primary energy reserves, triacylglycerols are most abundant lipid class
- Plant oils are usually richer in unsaturated fatty acid residues
Where are triacylglycerols made and stored
Can be made in the liver, adipocytes (cells of the fat tissue)
BUT most is stored in adipose tissue, little is stored in the liver
What happens to the triacylglycerols which are made in the liver but not stored there
Most are exported, packaged with other lipids & apoproteins to form ‘Very-Low Density lipoproteins’
VLDL are secreted directly into blood where they mature & function to deliver lipids to peripheral tissue
Mobilisation of stored fat in adipocytes occurs during times of metabolic need
How does this occur
- Requires the hydrolytic release of fatty acids & glycerol from triacylglycerol
- This is initaited by the hormone-sensitive lipase
How does hormone-sensitive lipase activated and how does it work?
- Activated: when phosphorlyated by a 3’,5’-cAMP-dependent protein kinase
- Action: removes the fatty acid from C-1 and/or C-3
What happens to the Hormone-sensitive lipase during periods of high insulin or glucose
It is dephosphorylated and inactived
This is because there is no need at this point to mobilise these stored fat at this point
What happens to glycerol which is released from stored fats by hormone-sensitive lipase
Glycerol which are released and transported via the blood to liver
Here they can be phosphorylated
Then can either (i) be used to form Triacylglycerol in liver or (ii) converted to DHAP for glycolysis/gluconeogenesis
What is the α-carbon or β-carbon on a triacylglycerol
The α-carbon is the one next to the carbonyl carbon
The β-carbon of the one adjacent to that
What occurs during β-oxidation
It is a series of enzyme catalysed reactions progressively degrading fatty acids by removing 2 carbon units & involves the oxidation of the β-carbon atom to the carbonyl group
Occurs in the mitocondria
What are the products of β-oxidation of fatty acids
Produces Acetyl CoA, NADH & FADH₂
β-oxidation occurs in the mitocondria
How does the fatty acid enter the mitocondria after entering the cell
- It is converted in the cytosol to its CoA derivative (priming)
- Catalysed by long-chain fatty ‘acyl-CoA synthetase’ (found in mitocondria outer membrane)
- Reaction is driven by exergonic hydrolysis of pyrophosphate
Once converted to Fatty acyl-CoA, how do there enter the mitocondria through its impermeable inner membrane
Via the Carnitine Shuttle
The Fatty acyl-CoA moves into the inter-membrane space and an enzyme called Carnitine palmitoyl transferase i, removes the Co-A group and replaces it with Carnitine on Fatty acid
This the can be translocated into the inner mitocondrial membrane
Synthesis of fatty acids need a large amount of Malonyl CoA
What affect does Malonyl CoA also have on the Carnitine Shuttle
Malonyl CoA inhibits Carnitine palmitoyl transferase i enzyme
So Fatty acyl Co-A cannot cross the mitocondrial membrane and be oxidised to create energy
Why might an individual have a Carnitine deficiency
- Liver disease
- Malnutrition/Vegetarian diets
- Patients with increased carnitine requirements (Pregnancy/burn victims)
- Haemodialysis
What happens in the first step of β-oxidation
- Formation of a trans-α, β double bond
- Via dehydrogenation (remove to hydrogens forming a C=C)
- by Flavoenzyme Acyl-CoA dehydrogenase
- Produces FADH₂
What happens in the second step of β-oxidation of fatty acids
- Hydration of double bond
- Using enzyme Enoyl-CoA hydratase
- Forns 3-L-hydroxyacyl-CoA
What happens in the 3rd step of β-oxidation of fatty acids
- NAD⁺ dependent dehydrogenation of the β-hydroxyacyl-CoA
- by 3-L-hydroxyacyl-CoA dehydrogenase (HAD)
- forms β-ketoacyl-CoA and NADH
What happens in the 4th step of β-oxidation once 3-ketoacyl CoA is formed
- Ca-cβ cleavage in a thiolysis reaction with CoA to form acetyl-CoA and a new acyl-CoA
Using enzyme β-ketoacyl-CoA thiolase
Why does the Mitocondria contain different 4 acyl-CoA dehydrogenases
For different specificities for chain length
Enzymes involved in the breakdown of Long-chain fatty are all multi-exyme complexes
What is the advantage if this
The ability to channel intermediates towards the final product
What is the output like for fatty acid oxidation
Fatty acid oxidation is hihgly excergonic
It produces around 129 ATP all together for a 16 carbon fatty acid
In the liver mitocondria, not all acetyl-CoA enters the TCA cycle
What hence is it used for instead
It can be converted into ‘ketone bodies’ by ketogenesis
Ketone bodies are an important energy source in heart and skeletal muscle (with being lipid soluble)
What does the synthesis of fatty acid involve
- Synthesis involves the combining of 2 carbon units (which derive from acetic acid)
- This requires acetyl-CoA & bicarbonate
- ATP and NADPH are also required
What happens in the 1st step of the synthesis reaction for fatty acids
- Acetyl CoA is produced by the oxidative decarboxylation of pyruvate by pyruvate dehydrogenase
- Involves the transfer of acetate units from mitocondrial Acetyl CoA to the cytosol
- Here it may be involved in the TCA cycle if there a demend for ATP, if not it is stored as fat
However, acetyl CoA cannot cross the mitochondrial membrane to get back into the cytosol
Only the acetyl potion enters the cytosol via the Tricarboxylate Transport system, How?
Acetyl CoA is converted into citrate through citrate synthase
Citrate can move through the tricarboxylate transport system into the cytosol
Here it is converted into oxaloacetate by ATP-citrate lyase
Then into malate by malate dehydrogenase
Then pyruvate is formed by malic enzyme, then pyruvate is returned into the system
How do you form Malonyl CoA from Acetyl-CoA in the second step of fatty acid biosynthesis
Acetyl CoA carboxylase will convert Acetly CoA into Malonyl CoA
Using ATP and CO₂
The fatty acid synthase enzyme is a multifunctional enzyme in eukaryotes which binds to Acetyl CoA
What two parts to it help it carry out its function
- Cysteine residue
- 4’-phosphopantetheine - which forms part of the acyl carrier protein
The Acyl carrier protein anchors the growing fatty acid
What happens in the 3rd step of fatty acid synthesis
- The acetate is transferred from acetyl CoA to Acyl carrier protein
- Here it is transferred to a cysteine residue
- The acetyl carrier protein takes a 3-carbon malonate protein from malonyl CoA (previous formed in step 2)
- The acetyl group on cysteine condenses with malonyl group forming 3-ketoacyl group
Once we have formed 3-ketoacyl group, what happens in step 4 of fatty acid sythesis
- The keto group is reduced to an alcohol
- A carbon=carbon is formed between C2 and C3
- The double bond is reduced
- Basically removing the ketone function groups of the carbon chain
- The cycle is then repeated through being transferred to cystein
What is the final product of fatty acid synthesis
Palmitate
Palmate is the final product of fatty acid synthesis, however it can be elongated to fit the cells need, how is this done?
It can be further elongated in the smooth endoplasmic reticulum or mitocondria
SER uses an ‘elongase’ system using malonyl-CoA 2C donor
How can fatty acids become desaturated
- Desaturases are present with SET and will de-saturate long chain fatty acids
- Add cis double bonds
Fatty acids can be stored as Triacylglycerols
How?
- Glycerol phosphate is the inital acceptor which is formed from glucose
- The Co-A are removed off the fatty acids as they are stuck together
What hormones regulate the metabolism of fatty acids
Insulin and Glucagon
They regulate opposing lipid pathways
