Lipid metabolism Flashcards
What are the 3 main sources fats are derived from?
- Diet
- De novo biosynthesis in the liver (De novo = from new/starting from the beginning)
- Storage depots in adipocytes - they can be hydrolysed to give free fatty acids and glycerol
How do triacylglycerols enter the circulatory system?
- Lipid digestion by lingual gastric and pancreatic lipase results in the formation of Monoacylglycerol (MAG), diacylglycerol (DAG) and free FAs
- A mixture of free fatty acids and mono- and diacylglycerols are solubilised.
- These then get taken up by the enterocytes (intestinal absorptive cells) within the intestine.
- The lipid digestion by lipases form monoacylglycerols (MAG), diacylglycerols (DAG) and free fatty acids (FAs) which join Bile Salts, Cholesterol, Lysophosphatidic Acid and fat soluble vitamins to form mixed micelles.
- The mixed micelles are absorbed by enterocytes.
- Triacylglycerols (TAGs) are resynthesised.
- TAGs are packaged into chylomicrons which then enter the lymphatic system and join the circulatory system.
Describe the process of beta-oxidation: Step 1
- Fatty acids are converted into an Acyl coA species
R-COOH + ATP + HS-CoA —> Acyl CoA + AMP + PPi
i.e. ATP –> AMP, 2 high energy bonds are used.
- Enzyme used: Acyl CoA Synthetase
- Thioester (HS-) linkage(ester‐bond between the COOH‐group of a fatty acid and a ‐SH‐group of a cysteine) of Acetyl CoA is good at binding groups and transferring the groups from one place to the other.
- HS-CoA links up with the fatty acid to form Acyl CoA.
- REMEMBER: 2 phosphoanhydride bonds (a ribose sugar and. three phosphate groups linked. by what are known as phosphoanhydride bonds) are used to generate the Acyl CoA from the Fatty Acid - that counts as 2 ATP
Describe the process of beta-oxidation: Carnitine Shuttle
Generation of the Acyl CoA species occurs on the outer mitochondrial membrane.
- To transport the species into the matrix, it is first coupled to a molecule of carnitine (catalyst - Carnitine Acyltransferase I) to form Acyl Carnitine.
- Acyl Carnitine is then transported across the membrane by a translocase.
- Carnitine Acyltransferase II then removes the acyl group from acyl carnitine and passes it on to CoA to form Acyl CoA and reform carnitine.
- The carnitine is moved back across the membrane to the cytoplasmic side by a translocase to pick up more Acyl CoA.
Describe the process of beta-oxidation: Beta-oxidation cycle
- Fatty Acyl CoA is OXIDISED and FAD is reduced to FADH2.
- The molecule produced is then HYDROLYSED, using 3-hydroxyacyl CoA hydrolase
- The product is then OXIDISED and NAD+ is reduced to form NADH using L-3-hydroxyacyl CoA dehydrogenase.
- Finally, you kick off a molecule of acetyl coA by bringing in a molecule of CoA and using b-ketothiolase.
- The remaining part of fatty acyl CoA which has been shortened by two carbons then repeats the cycle
- The β-oxidation reactions continue to consecutively remove 2-carbon units from the acyl CoA thereby producing acetyl CoA.
What is fatty acid biosynthesis/ lipogenesis?
Fatty Acid Biosynthesis involves two enzymes:
- Acetyl CoA Carboxylase
- Fatty Acid Synthase (FAS)
Fatty acids are formed sequentially by decarboxylative condensation reactions involving the molecules Acetyl-CoA and Malonyl-CoA.
After each round of elongation, the fatty acid undergoes reduction and dehydration by the sequential action of:
- Ketoreductase (KR)
- Dehydratase (DH)
- Enol Reductase (ER)
The growing fatty acyl group is linked to an acyl carrier protein (ACP).
Steps in the process of lipogenesis
Formation of 3C malonyl coA : USING acetyl coA CARBOXYLASE
Transfer of the malonyl to ACP to form Malonyl-ACP
Transfer acetyl from a CoA species to ACP to form acetyl-ACP.
Both combine/condense to form 5C compound so CONDENSATION co2 released to form 4C which is acetoacetyl-ACP.
REDUCTION of acetoacetyl ACP with ketoreducatase, this produces NADP+ from NADPH.
DEHYDRATION using dehydratase, produces 1 water.
REDUCTION using Enol reducatase which produces another NADP+.
Acetyl CoA (C2) + 7 Malonyl CoA (C3) + 14 NADPH +14 H+———->Palmitate (C16) + 7 CO2+ 6 H2O + 8 CoA-SH + 14 NADP+
4—->5
The process cycles a FURTHER 6 TIMES from step 4-7 to yield the 16C species palmitoyl-ACP, which is hydrolysed to give palmitate and ACP.
what is the overall equation of lipogenesis?
Acetyl CoA (C2) + 7 Malonyl CoA (C3) + 14 NADPH +14 H+ —-> Palmitate (C16) + 7 CO2+ 6 H2O + 8 CoA-SH + 14 NADP+
NOTE: There is one fewer H2O than expected because one of the H2O is used in the hydrolysis of Palmitoyl ACP to Palmitate and ACP
Similarities/differences between Synthesis and Degradation of Fatty Acids
Differences:
Carriers: CoA vs. ACP
Reducing Power: FAD/NAD+ vs. NADPH
Location: Mitochondrial matrix vs. cytoplasm
Where are fatty acids stored and how?
Triacylglycerol
In the cytoplasm of cells.
Adipocytes take on the role of fatty acid storage.
Why is having anhydrous food stores better than food being stored as glycogen?
Anhydrous food e.g. triacylglycerols is a good way as glyogen would cause people to be heavy as it requires water to be soluble.
Comment on the calorie from fatty acids compared to carbohydrate. What part of the body uses energy from beta-oxidation?
- Double that from carbohydrate.
- BRAIN does not use this.
What is beta oxidation and where does it happen
Uses fatty acids to make acetyl coA.
Takes place in Mitochondrial matrix
B-oxidation: what happens first and where?
Fatty acid + ATP + CoA to form acyl coA + AMP. 2 high energy bonds are used
That counts as 2 ATP!!!!!!!
Enzyme: Acyl coA synthetase.
ATP–> AMP
Happens in the outer mitochondrial membrane.
What is the purpose of the carnitine shuttle?
To transport the species into the matrix it is coupled to the molecule carnitine to form acyl carninitine.
Carnitine and Acyl carnitine are moved to and from the matrix by a translocase.
NOW ITS in the matrix where all the enzymes for beta oxidation are.
