Lipolysis of triglycerides in adipose tissue
The triglycerides deposited in adipose tissue are hydrolyzed by tissue lipases (triglyceride lipase, diglyceride lipase, monoglyceride lipase) into glycerine and free fatty acids.
The velocity of lipolysis of triglycerides changes under the influence of hormones, in stress, physical exercise, starvation, cooling. Under the influence of hormones (adrenaline, noradrenaline, glucagon) with participation of adenylate cyclase messenger system triglyceride lipase is activated by phosphorylation.
Fatty acids formed during lipolysis can pass from fat depots into blood plasma and be used by tissues and organs as an energy material. Fatty acids are transported as a complex with blood serum albumines. In tissues the complex breaks down, and fatty acids are exposed to β-oxidation. Partially they can be used for synthesis of lipids and cholesterol ethers.
1.3. Fatty acids oxidation
It occurs basically in the liver, kidneys, skeletal and heart muscles, in adipose tissues.
1. Fatty acid (FA) activation. It occurs in cytisole.
R–COOH + HS-CoA + ATP R–CO–S-CoA+AMP+PP1
fatty acid Acyl-CoA-synthetase
2. Transport of fa inside mitochondrion.
Acyl-CoA
Carnitine
Acylcarnitine
Acylcarnitine from cytoplasm diffuses through mitochondrion membrane. Enzyme is cytoplasm carnitine-acyl transferase. Then the reverse reaction starts - splitting of acylcarnitine with the assistance of HS-CoA and mitochondrion carnitine-acyl transferase:
acylcarnitine + НSCоА acyl-CоА + carnitine
It is believed to be the rate-limiting step in fatty acid oxidation.
3. Inside the mitochondrial matrix, fatty acids undergo β-oxidation.
a) dehydrogenation
FAD
FAD H2
Stearyl-CoA
α,β-Dehydrostearyl-CoA
There are three FAD-depending acyl-CoA-dehydrogenases, preferring short, medium and long-chain acyl radical.
b) hydration
Trans-dehydrostearyl CoA
L
β
Oxistearyl CoA
Enoil CoA
hydrase
Hydration is stereospecific. L-isomer is formed.
c) dehydrogenation.
β-Oxiacyl-CoA-dehydrase
L
β-Oxistearyl-CoA
β-Ketostearyl-CoA
NAD+
NADH + H+
Enzyme is 3-hydroxyacyl-CoA-dehydrogenase.
d) thiolase reaction.
3 Ketocyl CoA tyolase Palmitic acid preformed rest Palmityl-CoA Acetyl-CoA
Еnzyme is β-ketothiolase.
During this process, two-carbon molecules acetyl-CoA are repeatedly cleaved from the fatty acid. Acetyl-CoA can then enter the citric acid cycle, which produces NADH and FADH2. NADH and FADH2 are used in the electron transport chain to produce ATP.
Within oxidation of the fatty acid containing n carbon atoms, occurs (n/2 - 1) cycle of β-oxidation and all in all there will be n/2 molecules of acetyl-CoA.
Overall:
Stearyl-CoA + 8 FAD + 8 NAD + + 8 Н2О + 8 НSCоА
9 Acetyl-CoA + 8 FADН2 + 8 NADН + 8Н+
Balance of energy. At each cycle of β-oxidation one molecule FADН2 is formed and one molecule of NADН. In the oxidation in a respiratory chain and coupled with it phosphorylation they give: FADН2 - 2 molecules of ATP and NADН - 3 molecules ATP, i.e. there are 5 molecules of АТP is formed in one cycle. In the case of stearic acid - 5 х 8 = 40 molecules of АТP. 9 molecules of acetyl-CoA are formed; each of them in a Crebs cycle gives 12 molecules of АТP, all in all - 12 х 9 = 108 molecules of АTP.
Total: 40 + 108 - 1 (for the formation of FA active form) = 147 АТP.
Approximately 40% from all energy of FA oxidation in an organism is used for the АТP synthesis, and the rest is lost as heat.
Oxidation of FA with an odd number of carbon atoms
In lipids of different plants and some of sea organisms there are fatty acids with an odd number of atoms of carbon. They also undergo β-oxidation. However the end product of β-oxidations of the higher fatty acids with the odd number of carbon atoms is propionyl-CoA.
Propionyl-CoA turns into succinyl-CoA by means of two consecutive reactions - carboxylations and isomerizations:
Succinyl-CoA
ATP
ADP + H3PO4
Propionyl-CoA-carboxylase
(biotyprotein)
Methylmalonyl-CoA
Methylmalonyl-CoA
CoA-carbonylmutase
(B12-protein)
Further on succinyl-CoA joins the cycle of tricarboxylic acids.