Lipid Metabolism

Definition

- The process by which fatty acids are digested, broken down for energy, or stored in the human
body for later energy use. These fatty acids are a component of triglycerides, which make up
the bulk of the fat humans eat in foods like vegetable oils and animal products.
- Involves the synthesis of the structural and functional lipids (e.g., phospholipids, glycolipids,
sphingolipids, cholesterol, prostaglandins, etc.), such as those involved in the construction of cell
membranes.
- Includes the degradation or break down of lipids to satisfy the metabolic needs of the body (e.g.,
energy production).
- In animals, fats are obtained from food or are synthesized by the liver.
- In a constant state of dynamic equilibrium where some lipids are constantly being oxidized to
meet the body's metabolic needs, whereas others are being synthesized and stored for energy.

Lipid Metabolism – Digestion

- first step of Lipid Metabolism

- Breakage of triglycerides down into smaller monoglyceride units due to Lipase enzymes
- Occurs in the mouth via chemical digestion by lingual lipase
- Chemical digestion of lipids continues on in the stomach by gastric lipase, followed by the
beginning of mechanical digestion.
- In breaking down triglycerides, chemicals from the pancreas are secreted into the small
intestines, together with further mechanical digestion.
- Occurs until these become individual fatty acids
- Pancreatic Lipase – Signals Hydrolysis of Triglycerides

It is the pancreatic lipase that is responsible for signaling for the hydrolysis of the triglycerides into
separate free fatty acids and glycerol units.

Lipid Metabolism – Absorption and Transport

Short chain fatty acids can be absorbed in the stomach

- Starts within the small intestine wherein consumed triglycerides – which are esters of glycerol
and three fatty acids – are broken down into smaller chain fatty acids due to being emulsified by
Bile Salts.
- Once turned into smaller micelles, these triglycerides are then converted to monoglyceride
molecules by pancreatic lipases, which are enzymes that break down fats.
- Bile salts (contraction of gallbladder to release BS) and Pancreatic Lipase (from pancreas)
are released due to the presence of Cholecystokinin (CCK) a digestive hormone given off by the
intestinal cells within the intestinal mucosa.
- with these together, triglycerides are broken down into free fatty acids which move across
the intestinal membrane, where they re-combine to make triglycerides.
- here, Triglycerides are packaged along with cholesterol into phospholipid vesicles called
chylomicrons, which enable the transportation of fats and cholesterol (water-insoluble)
to move within the aqueous environment of lymphatic and circulatory systems.

- These chylomicrons then leave the enterocytes (a cell of the intestinal lining) via
exocytosis (cells excrete waste and other large molecules from the cytoplasm to the cell
exterior), enter the lymphatic capillaries (via lacteals in the villi of the intestine), and
eventually pass into the bloodstream, either going to the liver, or being stored in adipocytes
(Fat cells that comprise adipose (fat) tissue found throughout the body).
- The walls of blood capillaries have a surface enzyme called lipoprotein lipase ( hydrolyzes
triglycerides into fatty acids and glycerol) enabling them to pass through the capillary
wall into tissues, where they are oxidized for energy, or re-esterized for storage.
- Fats that are synthesized endogenously in the liver are packed into another type of
lipoprotein, the VLDL (very low-density lipoprotein), to be transported to tissues, where
triglycerides are extracted in the same way.
- When required, fat stores in adipose tissue are mobilized for energy production, by the
action of hormone sensitive lipase, which responds to hormones such as epinephrine.
Lipid Catabolism
- Glycerol is converted to glyceraldehyde 3-phosphate to get further oxidized and produce
energy
- Begins in the cytoplasm of cells as acyl-CoA synthetase uses the energy from cleavage of
an ATP to catalyze the addition of coenzyme A to the fatty acid
- The resulting acyl-CoA cross the mitochondria membrane and enter the process of beta
oxidation
- Once the chylomicrons (or other lipoproteins) travel through the tissues, these particles will
be broken down by lipoprotein lipase in the luminal surface of endothelial
cells in capillaries to release triglycerides.[13] Triglycerides will get broken down into fatty acids
and glycerol before entering cells and remaining cholesterol will again travel through the
blood to the liver.[14]
- However, the main steps of fatty acids catabolism occur in the mitochondria.[15] Long chain
fatty acids (more than 14 carbon) need to be converted to fatty acyl-CoA in order to pass
across the mitochondria membrane.[6]
- Fatty acid catabolism begins in the cytoplasm of cells as acyl-CoA synthetase uses the
energy from cleavage of an ATP to catalyze the addition of coenzyme A to the fatty acid.
[6]
The resulting acyl-CoA cross the mitochondria membrane and enter the process of beta
oxidation.
LIPID BIOSYNTHESIS

- In dietary fats, storage lipids stored in the adipose tissues are one of the main sources of energy for living organisms.
- membrane lipid biosynthesis occurs in the endoplasmic reticulum membrane
- Triglycerides biosynthesis occurs in the cytosol
- the precursor for fatty acids is acetyl CoA and it occurs in the cytosol of the cell
- 70% of cholesterol biosynthesis occurs in the cytosol of liver cells.

LIPOLYSIS
- Catabolic Reaction
- Occurs within the Cytoplasm
- Process involving hydrolysis wherein triglycerides are broken down into their two principal
components, fatty acids and glycerol.
- The glycerol that is released from triglycerides after lipolysis directly enters the glycolysis
pathway as DHAP (Dihydroxyacetone phosphate - enzyme catalyzes the isomerization of
a three-carbon sugar into another three-carbon sugar).

Beta (β)-oxidation
- “Fatty acid oxidation”
- Occurs within the Cytoplasm
- breakdown or conversion of fatty acids into fatty acyl CoA molecules.
o fatty acyl CoA combines with carnitine to create a fatty acyl carnitine molecule
( which helps to transport the fatty acid across the mitochondrial membrane).
o Inside the mitochondrial matrix, the fatty acyl carnitine molecule is converted back
into fatty acyl CoA and then into acetyl CoA.
Each round of beta-oxidation removes 2 carbons from the fatty acid chain, releasing one acetyl-CoA, which can
then be oxidized in the citric acid cycle.

Beta-oxidation also produces several high-energy molecules which are fed directly to the electron transport
system.

- The main products of the beta oxidation pathway are acetyl-CoA (which is used in the citric
acid cycle to produce energy), NADH and FADH.[15] The process of beta oxidation requires
the following enzymes: acyl-CoA dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl-CoA
dehydrogenase, and 3-ketoacyl-CoA thiolase.[14] The diagram to the left shows how fatty
acids are converted into acetyl-CoA. The overall net reaction, using palmitoyl-CoA (16:0) as
a model substrate is:
- 7 FAD + 7 NAD+ + 7 CoASH + 7 H2O + H(CH2CH2)7CH2CO-SCoA → 8 CH3CO-SCoA + 7
FADH2 + 7 NADH + 7 H+

KETOGENESIS
- acetyl CoA is diverted to create ketone bodies in case of the creation of excessive acetyl CoA from the
oxidation of fatty acids.
- During glucose starvation, ketone bodies are an important source of fuel, especially for the brain.

LIPOGENESIS
- Anabolic Reaction
- takes place in the cytoplasm of (adipocytes) fat cells and (hepatocytes) liver cells
- creates lipids (fat) from the acetyl CoA
- begins with acetyl CoA and advances by the subsequent addition of two carbon atoms from another acetyl CoA;
this process is repeated until fatty acids are the appropriate length.
Fats are triglycerides, they are esters of glycerol and three fatty acids.

Fats can come from the diet, from stores in adipose tissue, or can be synthesized from
excess dietary carbohydrates in the liver.

During glucose starvation, ketone bodies are an important source of fuel, especially for the brain.

However, ketone bodies are acidic, and when produced in excess, can overwhelm the buffering capacity of blood
plasma, resulting in metabolic acidosis, which can lead to coma and death.

Ketoacidosis is a serious complication of diabetes, in which cells must oxidize fats for fuel as they cannot utilize
glucose.

Extreme diets that are excessively low in carbohydrates and high in fat may also result
in ketoacidosis.
On the other hand, diets that are high in carbohydrates generate excess acetyl-CoA that can be converted into
fatty acids.

Synthesis of fatty acids from acetyl-CoA is stimulated by citrate, a marker of energy abundance, and inhibited by
excess of fatty acids.

Fatty acids can be converted into triglycerides, for storage or synthesis of other lipids, by combining with glycerol
derived from a glycolysis intermediate.