Fat metabolism Flashcards
What are the three main categories that lipid use is defined?
1) Bilayer (phosphate bilayer)
2) Energy Stores
3) Intra and extra-cellular signalling
There are some others than are fat-soluble vitamins that have regulatory/ co-enzyme functions
How are lipids transported? Why?
Compartmentalised or transported in association with protein
-they are insoluble
What are fatty acids?
-carboxylic acids with long chain hydrocarbon side groups
Where can substantial amounts of free fatty acids be found?
Blood plasma
-transported on serum albumin to point of consumption
Where is the only place that can’t rely on fat metabolism?
The brain as the serum albumin can’t cross the cell membrane
What type of lipids are fats and oils of plants and animals?
Tricylglycerols
What types of fatty acids are attached to each carbon?
Carbon 1: Usually saturated
Carbon 2: Usually unsaturated
Carbon 3: Either
How is glycerol formed from triacyglycerols?
They are Eserified via their carboxyl groups which results in a loss of charge
What are adipocytes?
They are specialised molecules for the synthesis and storage of Triacyglycerols (TAG’s)
What is the fat content for normal humans?
21% for men
26% for women
Where is the fat stored in the body?
1) Adipocytes: - white adipose tissue, TAG’s coalesce to form oily droplets (bady’s main energy reserve)
2) Liver, but most is exported and packaged with other lipids & apoproteins to form VLDL (Very-Low-Density-Lipoproteins
When does the mobilisation of fat occur?
Occurs during times of metabolic need which is initiated by hormone-sensitive lipase
What does hormone-sensitive lipase do?
Removes the fatty acid from C-1 and/or C-3 leaving a lipid with only 1 or 2 hydrocarbon chains
-the remaining chains are removed by diacylglycerol (if 2 chainz present) or monoacylglycerol (if 1 chain is present)
When is hormone-sensitive lipase activated?
- When phosphorylated by a cyclic AMP (cAMP)
- when glucagon/epinephrine binds to cells
What is beta oxidation?
A series of catalysed reactions progressively degrading fatty acids by removing 2 Carbon units & involves the oxidation of the Beta Carbon atom to the carboxyl group
Where does beta oxidation take place and what does it produce?
Located in mitochondria
Produces AcetylCoA, NADH & FADH2
What occurs after Long Chain Fatty Acids (LCFA’s) enter the cell?
- Converted in the cytosol to its CoA derivative (known as priming)
- Catalysed by Long-Chain fatty acetyl-CoA synthatases known as Thiokinases
What is the reaction driven by?
Exergonic hydrolysis of pyrophosphate
How are acyl-CoA’s transported across an impermeable mitochondrial membrane?
- Carnitine Shuttle
- fatty acids transfer its acyl part on to carnitine forming acylcarnitine
How does acylcarnitine tranported into matrix?
Exchanged with free carnitine in opposite direction by Carnitine palmitoyltransferase I (CPT-1)
How is carnitine obtained?
In the diet from meat
-synthesised from lysine and methionine by liver and kidneys
How can carnitine deficiencies arise?
1) Liver disease
2) Malnutrition/Vegetarian diets
3) Pregnancy or Burns victims which require increased carnitine
4) Haemodialysis
How do short&medium fatty acids enter the mitochondria?
Chains with less than 12 carbons can enter without the carnitine shuttle and is not dependent on CPT-1
What are the reactions of the Fatty acyl-CoA sequence?
1) Formation of a trans-a, beta double bond
- Caused by dehydrogenation and produces FADH2
2) Hydration of the double bond to form 3-L-hydroxyacyl-CoA
3) NAD+ dependent dehydrogenation of the beta-hydroxyacyl-CoA
- forms beta-ketoacyl-CoA and NADH
4) alpha Carbon - beta Carbon cleavage in a thiolysis reaction to form Actyl-CoA and a new acyl-CoA
What is acetyl-CoA useful for?
Links fatty acid oxidation reactions & gluconeogenesis
How many times are the beta oxidation reactions carried out per fatty acid?
(n/2)-1 times where n= carbon number which must be even
What does each cycle produce?
- an acetyl group
- 1 NADH
- 1 FADH2
What happens to FADH2 after beta oxidation?
reoxidised by the mitochondrial electron-transport chain to reduce CoQ
What is MCAD deficiency?
Medium-Chain Fatty Acyl CoA dehydrogenase deficiency
- autosomal recessive disorder
- decreased ability to oxidise fatty acids with 6 to 10 C
- Severe hypoglycemia due to increased glucose reliance
-Cause of 10% of Sudden Infant Death Syndrome due to human milk being that length
What is the ATP output for each fatty acid?
- highly exergonic
- each FADH2 provides 2ATP
- each NADH provides 3ATP
- each Acetyl CoA provides 12 ATP in the TCA cycle
Take away 2ATP from total due to it being used in fatty acyl-CoA formation
So a 16C acid produces 129ATP
What are Ketone bodies?
Important energy sources in heart & skeletal muscle
- are soluble so no need for lipoproteins or albumin
- produced when acetyl-CoA exceeds oxidative capacity
- Used in proportion to blood by extrahepatic (outside the liver) tissues
Examples of ketone bodies?
- Acetoacetate
- 3-hydroxybutyrate
- Acetone
How is acetyl CoA produced?
the oxidative carboxylation of pyruvate by pyruvate dehydrogenase
What is the ‘Tricarboxylate Transport System’ (TCA Cycle)?
1) Oxoloacetate is reduced to malate by malate dehydrogenase
2) Malate is oxidatively decarboxylated to pyruvate by malic enzyme
NOT COMPLETED QUESTION CARD
How isthe carboxylation of Acetyl-CoA to Malonyl CoA achieved?
- Catalysed by Acetyl CoA Carboxylase
- Addition of CO2 through breakdown of ATP to release energy for reaction
- Biotin is the coenzyme
How is palmitic acid formed? first 4 reactions
1) Acetate is transferred from acetyl CoA to the -SH group of ACP
2) The 2C unit is transferred to the thiol group of a cysteine residue
3) The ACP accepts a 3C malonate unit from malonyl CoA
4) The acetyl group on the cysteine residue condenses with the malonyl group on ACP - CO2 is released and the loss of free energy drives the reaction
How is palmitic acid formed? Steps 5,6,7
5) The keto group is reduced to an alcohol
6) A molecule of water is removed to introduce a double bond between carbons 2&3
7) The double bond is reduced
What is the final stoichiometry of the formation of palmitate
8Acetyl-CoA + 14NADPH + 7ATP = Palmitate + 14NADP + 8CoA + 6H2O + 7ADP + 7Pi
What is the structure of palmitate?
16Carbon fully saturated
How can Palmitate be further elongates and where?
Elongated in the Smooth Endoplasmic reticulum (SER) or mitochondria onlt 2C added
-SER uses elongase system where Malonyl-CoA is the 2C donor and NADPH supplies the electrons
How are fatty acids desaturated?
Desaturases are present in SER and will de-saturate long-chain fatty acids by adding double bonds
How are certain polyunsaturated fatty acids obtained?
In the diet through red meats predominantly
How are fatty acids regulated?
Insulin and Glucagon regulate the opposing lipid pathways
