Metabolism 6: Lipid Metabolism Flashcards
In mammals what cells take the role of fatty acid storage?
ADIPOCYTES
In times of starvation, the fatty acids that are stored in adipocytes can be used to provide energy.
Three sources of fat?
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
Describe how fats are emulsified by bile*
Bile salts are generated by the liver and stored in the gall bladder. During digestion they are secreted into the intestine.
Bile salts have a hydrophobic face and a hydrophilic face (which has many carboxyl and hydroxyl groups) which allows the bile salts to interact with solute and triacylglycerols.
Bile salts present the hydrophobic face to the triacylglycerols and the hydrophilic face to the solvent.
That gets it into a soluble form so lipases can come to start breaking them down.
Notes:
Lack of bile salts causes fats to pass through the digestive tract undigested and unabsorbed resulting in steatorrhea (fatty stool).
A Mixed Micelle forms which is a mixture of triacyl-, diacyl-, monoacylglycerols and free fatty acids.
Describe oxidation of fatty acids
This process is known as b-oxidation and it occurs in the MITOCHONDRIA resulting in the formation of acetyl CoA.
2 phosphoanhydride bonds are used to generate the Acyl CoA from the Fatty Acid! That counts as 2 ATP!
fatty acid + atp + HS-coa ->fatty acyl coa + amp + ppi
Enzyme is acetyl CoA synthetase
This reaction takes place on the OUTER MITOCHONDRIAL MEMBRANE
How is the Acetyl CoA transferred to the matrix?
To transport the species into the matrix, it is firstly 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.
What happens to the fatty acyl coa in the b-oxidation Cycle
Fatty Acyl CoA is oxidised and FAD is reduced to FADH2.
The molecule produced is then hydrolsed.
The product is then oxidised and NAD+ is reduced to form NADH.
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
BASICALLY, THE ORIGINAL FATTY ACYL CoA HAS BEEN SHORTENED BY 2 CARBONS
What is the b-oxidation of Palmitic Acid
from just 7 b-oxidation cycles, 16 carbon palmitoyl CoA molecule produces 8 Acetyl CoA molecules.
REMEMBER: During each cycle, 1 NADH and 1 FADH2 are produced.
Overall reaction:
Palmitoyl CoA + 7FAD + 7NAD+ + 7H2O + 7CoA —-> 8 Acetyl CoA + 7FADH2 + 7NADH
What is needed for the Acetyl CoA formed from b-oxidation to enter the TCA cycle
b-oxidation and carbohydrate metabolism need to be balanced.
This is because OXALOACETATE is needed for entry of Acetyl CoA into the TCA cycle.
When fat breakdown predominates (e.g. when fasting/starving) what does acetyl CoA forms:
KETONE BODIES. such as:
Acetoacetate
D-3-hydroxybutyrate
Acetone
How much ATP is produced from b-oxidation of Palmitate
131 made
2 used
129 net
What is Lipogenesis
Fatty Acid Biosynthesis, it 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.
Acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14 H+ —–> Palmitate + 7 Co2 + 6 H2O + 8 CoA-SH + 14 NADP+
There is one fewer H2O than expected because one of the H2O is used in the hydrolysis of Palmitoyl ACP to Palmitate and ACP
What is Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD)
Autosomal Recessive - occurs predominantly in caucasians.
Occurs in 1 in 10,000 live births
Accounts for 1 in 100 deaths from Sudden Infant Death Syndrome (SIDS)
If diagnosed - avoid fasting and have a rich carbohydrate diet.
Part of the heel prick test
Patients with loss of appetite may need IV glucose to make sure that the body isn’t dependant on fatty acids for energy.
What is Primary Carnitine Deficiency
Autosomal recessive
Carnitine is needed to chaperone the Acyl group into the mitochondrial matrix from the outer membrane of the mitochondrion.
Carnitine can be given as a supplement to treat this deficiency.
