Lipid Metabolism refers to the biochemical processes involved

in the digestion, absorption, transport, storage, and utilization of

lipids within the body. Lipids, primarily in the form of
triglycerides, cholesterol, and phospholipids, serve as essential
energy sources and structural components of cell membranes.

Fats (or triglycerides) within the body are ingested as food

or synthesized by adipocytes or hepatocytes from
carbohydrate precursors. Lipid metabolism entails the
oxidation of fatty acids to either generate energy or
synthesize new lipids from smaller constituent molecules.
Lipid metabolism is associated with carbohydrate
metabolism, as products of glucose (such as acetyl CoA)
can be converted into lipids.

Figure 1. A triglyceride molecule (a) breaks down into a monoglyceride

(b).
Lipid metabolism begins in the intestine where
ingested triglycerides are broken down into smaller chain
fatty acids and subsequently into monoglyceride
molecules by pancreatic lipases, enzymes that break
down fats after they are emulsified by bile salts. When food
reaches the small intestine in the form of chyme, a digestive
hormone called cholecystokinin (CCK) is released by

 intestinal cells in the intestinal mucosa. CCK stimulates the
release of pancreatic lipase from the pancreas and
stimulates the contraction of the gallbladder to release
stored bile salts into the intestine. CCK also travels to the
brain, where it can act as a hunger suppressant.

Figure 2. Chylomicrons contain triglycerides, cholesterol molecules,

and other apolipoproteins (protein molecules). They function to carry
these water-insoluble molecules from the intestine, through the
lymphatic system, and into the bloodstream, which carries the lipids to
adipose tissue for storage.
Together, the pancreatic lipases and bile salts break down
triglycerides into free fatty acids. These fatty acids can be
transported across the intestinal membrane. However, once
they cross the membrane, they are recombined to again
form triglyceride molecules. Within the intestinal cells, these
triglycerides are packaged along with cholesterol molecules

in phospholipid vesicles called chylomicrons. The
chylomicrons enable fats and cholesterol to move within the
aqueous environment of your lymphatic and circulatory
systems. Chylomicrons leave the enterocytes by exocytosis
and enter the lymphatic system via lacteals in the villi of the
intestine. From the lymphatic system, the chylomicrons are
transported to the circulatory system. Once in the
circulation, they can either go to the liver or be stored in fat
cells (adipocytes) that comprise adipose (fat) tissue found
throughout the body.

1. Digestion and Absorption:

• Dietary lipids are initially emulsi ed by bile salts in the small

intestine, enhancing their breakdown by pancreatic lipases.
• Lipases hydrolyze triglycerides into free fatty acids and
monoglycerides, which are absorbed by enterocytes
(intestinal cells).
• Inside enterocytes, free fatty acids and monoglycerides
reassemble into triglycerides, which are then packaged into
chylomicrons and released into the lymphatic system.

2. Transport and Distribution:

• Chylomicrons transport triglycerides and cholesterol from the

intestine through the lymphatic system into the bloodstream.
• Lipoproteins, including chylomicrons, VLDL (very-low-density
lipoproteins), LDL (low-density lipoproteins), and HDL (high-
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 density lipoproteins), facilitate lipid transport to tissues. Each
lipoprotein type has a speci c function in lipid transport and
distribution.

3. Storage and Mobilization:

• In adipose tissue, triglycerides are stored in large quantities,

serving as an energy reservoir.
• Hormones such as epinephrine and glucagon stimulate
lipolysis, the hydrolysis of stored triglycerides into free fatty
acids and glycerol, which are then released into the
bloodstream to be used by other tissues.

4. Fatty Acid Oxidation (Beta-Oxidation):

• Free fatty acids undergo beta-oxidation in the mitochondria of

cells, where they are broken down into acetyl-CoA units.
• Acetyl-CoA then enters the citric acid (Krebs) cycle, producing
ATP, NADH, and FADH2, which are essential for cellular
energy production.

5. Ketogenesis:

• In cases of prolonged fasting or low carbohydrate availability,

the liver converts excess acetyl-CoA into ketone bodies
(acetoacetate, beta-hydroxybutyrate, and acetone).
• Ketone bodies serve as an alternative energy source,
particularly for the brain and muscle tissue.
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 If excessive acetyl CoA is created from the oxidation of fatty
acids and the Krebs cycle is overloaded and cannot handle
it, the acetyl CoA is diverted to create ketone bodies.
These ketone bodies can serve as a fuel source if glucose
levels are too low in the body. Ketones serve as fuel in times
of prolonged starvation or when patients suffer from
uncontrolled diabetes and cannot utilize most of the
circulating glucose. In both cases, fat stores are liberated to
generate energy through the Krebs cycle and will generate
ketone bodies when too much acetyl CoA accumulates.
In this ketone synthesis reaction, excess acetyl CoA is
converted into hydroxymethylglutaryl CoA (HMG CoA).
HMG CoA is a precursor of cholesterol and is an
intermediate that is subsequently converted into β-
hydroxybutyrate, the primary ketone body in the blood.

Figure 4. Excess acetyl CoA is diverted from the Krebs cycle to the
ketogenesis pathway. This reaction occurs in the mitochondria of liver
cells. The result is the production of β-hydroxybutyrate, the primary
ketone body found in the blood.

6. Fatty Acid and Triglyceride Synthesis
(Lipogenesis):

When glucose levels are plentiful, the excess acetyl CoA

generated by glycolysis can be converted into fatty acids,
triglycerides, cholesterol, steroids, and bile salts. This
process, called lipogenesis, creates lipids (fat) from the
acetyl CoA and takes place in the cytoplasm of adipocytes
(fat cells) and hepatocytes (liver cells). When you eat more
glucose or carbohydrates than your body needs, your
system uses acetyl CoA to turn the excess into fat. Although
there are several metabolic sources of acetyl CoA, it is most
commonly derived from glycolysis. Acetyl CoA availability is
significant, because it initiates lipogenesis. Lipogenesis
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. Because this is a bond-creating anabolic process,
ATP is consumed. However, the creation of triglycerides and
lipids is an efficient way of storing the energy available in
carbohydrates. Triglycerides and lipids, high-energy
molecules, are stored in adipose tissue until they are
needed.
Although lipogenesis occurs in the cytoplasm, the necessary
acetyl CoA is created in the mitochondria and cannot be
transported across the mitochondrial membrane. To solve
this problem, pyruvate is converted into both oxaloacetate
and acetyl CoA. Two different enzymes are required for
these conversions. Oxaloacetate forms via the action of
pyruvate carboxylase, whereas the action of pyruvate
dehydrogenase creates acetyl CoA. Oxaloacetate and
acetyl CoA combine to form citrate, which can cross the
mitochondrial membrane and enter the cytoplasm. In the
 cytoplasm, citrate is converted back into oxaloacetate and
acetyl CoA. Oxaloacetate is converted into malate and then
into pyruvate. Pyruvate crosses back across the
mitochondrial membrane to wait for the next cycle of
lipogenesis. The acetyl CoA is converted into malonyl CoA
that is used to synthesize fatty acids. Figure 6 summarizes
the pathways of lipid metabolism.

• Excess carbohydrates and proteins can be converted into

fatty acids in the liver through lipogenesis.

• Synthesized fatty acids are esteri ed to form triglycerides,
which are then transported to adipose tissue for storage.

Importance in Metabolism:

Lipid metabolism is crucial for maintaining energy homeostasis,

cellular function, and structural integrity of cell membranes.
Dysregulation of lipid metabolism is associated with metabolic
disorders such as hyperlipidemia, atherosclerosis, obesity, and
non-alcoholic fatty liver disease, underscoring its signi cance in
human health.

~Physiosource
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