Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown and storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In animals, these fats are obtained from food and are synthesized by the liver. Lipogenesis is the process of synthesizing these fats. The majority of lipids found in the human body from ingesting food are triglycerides and cholesterol.[4] Other types of lipids found in the body are fatty acids and membrane lipids. Lipid metabolism is often considered as the digestion and absorption process of dietary fat; however, there are two sources of fats that organisms can use to obtain energy: from consumed dietary fats and from stored fat.[5] Vertebrates (including humans) use both sources of fat to produce energy for organs such as the heart to function. Since lipids are hydrophobic molecules, they need to be solubilized before their metabolism can begin. Lipid metabolism often begins with hydrolysis, which occurs with the help of various enzymes in the digestive system.Lipid metabolism also occurs in plants, though the processes differ in some ways when compared to animals.[8] The second step after the hydrolysis is the absorption of the fatty acids into the epithelial cells of the intestinal wall.[6] In the epithelial cells, fatty acids are packaged and transported to the rest of the body.[9]
Metabolic processes include lipid digestion, lipid absorption, lipid transportation, lipid storage, lipid catabolism, and lipid biosynthesis. Lipid catabolism is accomplished by a process known as beta oxidation which takes place in the mitochondria and peroxisome cell organelles.
3. INTRODUCTION
LIPID:- Esters of fatty acid with alcohol.
It is a catabolic pathway of lipid or fats.
Degradation is done by oxidation of fatty acids.
In human body, fats are stored in various forms in adipose tissue and the major
form is triglycerides.
A triglyceride consists of the glycerol to which the 3 fatty acids are joined by
the ester linkage.
The fatty acids are distributed all over the body and from their they enter into
the blood. Through the blood they are distributed to actually all the cells that
can metabolize fatty acids.
The fatty acid then moves inside the cytoplasm of the target cell. For instance,
1. Alpha oxidation- in peroxisomes
2. Beta oxidation- in mitochondria
3. Omega oxidation- in endoplasmic reticulum
4. TYPES OF FATTYACID OXIDATION
Fatty acids can be oxidized by:
1. Alpha oxidation- oxidation occurs at alpha position.
2. Beta oxidation- oxidation occurs at beta position.
3. Omega oxidation- oxidation occurs at omega position.
Positions in fatty acids:-
𝜔𝛽𝛼
𝐶𝐻2-(𝐶𝐻2)11-𝐶𝐻2-𝐶𝐻2-𝐶𝐻2-𝐶𝑂𝑂−
5. 1) BETA(𝛽) OXIDATION
The fatty acids in the body are mostly oxidized by 𝜷 − oxidation.
𝜷oxidation may be defined as the oxidation of fatty acids on the
βcarbon atom. This result in the sequential removal of a two carbon
fragment, Acetyl CoA.
Beta oxidation involves three stages:-
1. Activation of fatty acid.
2. Transport of Acyl CoA into mitochondria.
3. 𝜷 oxidation proper.
6. 1. FATTYACIDACTIVATION:-
Fatty acids are activated to acyl
CoA by acyl CoA synthetases.The
reaction occurs in two steps and
requires ATP,CoA and 𝑀𝑔++
.
Fatty acid reacts with ATP to form
acyladenylate which then
combines with coenzymeA to
produce acyl CoA.
In the activation two high energy
ATP are utilized.
𝐶𝐻2-(𝐶𝐻2)11-𝐶𝐻2-𝐶𝐻2-𝐶𝐻2-𝐶𝑂𝑂−
ATP
Thiokinase
PPi
𝑃𝑌𝑅𝑂𝑃𝐻𝑂𝑆𝑃𝐴𝑇𝐴𝑆𝐸
2Pi
𝐶𝐻2-(𝐶𝐻2)11-𝐶𝐻2-𝐶𝐻2-𝐶𝐻2-CO-AMP
Acyl adenylate
CoASH
AMP
𝐶𝐻2-(𝐶𝐻2)11-𝐶𝐻2-𝐶𝐻2-𝐶𝐻2-CO- SCoA
Acyl CoA
8. 3.𝜷 𝑶𝑿𝑰𝑫𝑨𝑻𝑰𝑶𝑵 𝑷𝑹𝑶𝑷𝑬𝑹
Each cycle of 𝛽 oxidation, liberating a two carbon unit acetyl CoA, occurs
in a sequence of 4 sections:-
1. Oxidation- Acyl CoA undergoes dehydrogenation by an FAD-
dependent flavoenzyme, acyl CoA dehydrogenase. A double bond is
formed between 𝛼 𝑎𝑛𝑑 𝛽 carbons.
2. Hydration-Enoyl CoA hydratase brings about the hydration of the
double bond to form 𝛽hydroxyacyl CoA.
3. Oxidation - 𝛽hydroxyacyl CoA dehydrogenase catalyses the second
oxidation and generates NADH. The product formed is 𝛽ketoacyl CoA.
4. Cleavage – The final reaction in 𝛽 oxidation is the liberation of a 2
carbon fragment,acetyl CoA from acyl CoA. This occurs by a thiolytic
cleavage catalyzed by 𝛽ketoacyl CoA thiolase (or simply thiolase).
9.
10. Oxidation of palmitoyl CoA:-
The summary of 𝛽 oxidation of palmitoyl CoA is shown below:-
Palmitoyl CoA + 7 CoASH+ 7FAD+ 7NA𝐷+
+ 7 𝐻2O 8 acetyl CoA + 7 𝐹𝐴𝐷𝐻2
+ 7 NADH + 7𝐻+
Energy Yield:-
2.5 ATPs per NADH= 17.5
1.5 ATPs per 𝐹𝐴𝐷𝐻2=10.5
10ATPs per acetyl CoA= 80
Total= 108 ATPs
2ATP equivalents(ATP -> AMP + PPi and Ppi ->2Pi) consumed during activation of palmitate to
Palmitoyl CoA
Net energy output = 108-2= 106ATP
11. 2) ALPHA(𝛼) 𝑂𝑋𝐼𝐷𝐴𝑇𝐼𝑂𝑁
The alpha oxidation of long chain fatty acids occurs at the
second position of the chain.
This involves the decarboxylation process for the removal of
single carbon atom at one time with the resultant production
of an odd chain fatty acid that can be subsequently oxidized
by beta oxidation for energy production.
No prior activation of the fatty acid is required.
In microsomes of brain and liver.
Alpha oxidation is most suited for the oxidation of phytanic
acid, produced from dietary phytol, a constituent of milk
lipids and animal fats.
12. Alpha oxidation is most suited for the
oxidation of phytanic acid, produced
from dietary phytol, a constituent of
milk lipids and animal fats.
Phytanic acid is a signinficant
constituent of milk lipids and animal
fats.
Normally it is metabolized by an
initial alpha hydroxylation followed
by dehydrogenation and
decarboxylation.
Beta oxidation cannot occur initially
because of the presence of methyl
groups, but it can proceed after
decarboxylation.
The whole reaction produces three
molecules of propionyl co A, three
molecules of acetyl co A and one
molecule of iso butyryl co A.
13. Clinical Significance:-
Refsum’s disease- is a neurocutaneous syndrome that is characterized
biochemically by the accumulation o fphytanic acid in the plasma and
tissues. Patients with refsum disease are unable to degrade phytanic acid
because of a deficient activity of phytanic acid oxidase enzyme catalyzing
the first step of phytanic acid oxidation.
14. 3) OMEGA(𝝎) OXIDATION
Omega oxidation is the alternative pathway to beta oxidation
that, instead of involving the beta carbon, involve the oxidation
of the omega carbon.
The process is normally a minor catabolic pathway for medium
chain fatty acids (6-12 C atoms) such as lauric acid(12 C),
caprylic acid(8 C), capric acid(10 C).
It occurs in endoplasmic reticulum in liver,brain and kidney.
It uses “the mixed function oxidase” type of reaction.
In omega oxidation, oxidation of fatty acid forms dicarboxylic
fatty acid.
15. STEPS:-
Lauric acid is converted to an alcohol
by the addition of –OH group to
omega carbon with the help of mixed
function oxidase (widely distributed
enzyme that carry out oxidation
reduction reaction).
Then omega hydroxy fatty acid is
converted to aldehyde group with the
help of alcohol dehydrogenase which
converts NAD to NADH.
Then the product formed converts to
dicarboxylic acid with the help of
aldehyde dehydrogenase and converts
NAD to NADH indicating that
oxidation is taking place.