Lipid Metabolism Part2

Figure 18.
3: Overview of
fat digestion, absorption,
storage, and mobilization
in the human.
Figure 18.4: Action of bile salts in
emulsifying fats in the intestine.
"Good/Bad" Cholesterol
LDL called bad cholesterol because of

link to atherosclerosis
HDL called good cholesterol because
high HDL levels counter
atherosclerosis by transporting
cholesterol back to the liver from
peripheral tissues
LIPOLYSIS;
mobilization of
lipids
Fatty Acid vs. Glucose Oxidation:
A Comparison
• Spiral fatty acid oxidation produce net 95

ATP molecules by oxidation of 12 carbon
atom fatty acid (lauric acid)
• 1 Glucose molecule (6 carbon atoms)

produces 36-38 ATP molecules
In normally functioning body,
certain organs use both fuels,
others prefer glucose, and still
others prefer fatty acids.
Generalizations:
1. Skeletal muscle uses glucose
(glycogen) when in an active state.
In a resting state, it uses fatty
acids.
2. Cardiac muscle depends first on
fatty acids and secondary on ketone
bodies, glucose and lactate.
3. The liver uses fatty acids as the

preferred fuel.
4. Brain function is maintained by

glucose and ketone bodies.
Citric Acid Cycle
▪ Oxaloacetate is produced from malate and also
produced by the carboxylation of
phosphoenolpyruvate (glycolysis)
- pyruvate can be converted to oxaloacetate by
pyruvate carboxylase
▪ Low glucose supply also slows down the citric acid

cycle
▪ Under low supply of oxaloacetate the acetyl CoA

will be in excess (increased concentration)
▪ As a consequence the excess acetyl CoA is

converted to ketone bodies
❑ When there is adequate balance
between lipid and carbohydrate
metabolism , most of the acetyl
CoA produced from the ɞ-
oxidation pathway is further
processed through the citric acid
cycle.
Ketone Bodies
• Ketone bodies: acetone, -
hydroxybutyrate, and acetoacetate;
– are formed principally in liver mitochondria.
Formation occurs when the amount of acetyl CoA produced is

excessive compared to the amount of oxaloacetate available to
react with it and take it into the Citric Acid Cycle; for example:
– intake is high in lipids and low in carbohydrates.

– diabetes is not suitably controlled.
– starvation.
Ketone Bodies
HS-CoA
O O O
2 CH3 C-SCoA CH3 CCH2 C-SCoA
Acetyl-CoA Acetoacetyl-CoA
O NADH OH
CH3 -C-CH2 -COO- CH3 -CH-CH2 -COO-
A cetoacetate NAD+ + H+ -Hyd roxybutyrate
CO2 O
CH3 -C-CH3
Acetone
Summary of Ketogenesis
Ketogenesis
• Ketogenesis involves the production of
ketone bodies from acetyl CoA
• Synthesis of ketone bodies from acetyl CoA

primarily in liver mitochondria -- diffused into
blood stream and transported to peripheral
tissues
• During starvation or uncontrolled diabetes,
ketone bodies accumulate in the blood and
excess is secreted in the urine.
Ketonemia –excess accumulation of ketone bodies in blood
Ketonuria – ketone bodies are excreted in the urine
Ketosis – overall accumulation of ketone bodies in the
blood and urine
❖ In diabetes mellitus the body is unable to oxidize

carbohydrates and instead oxidizes fats, leading to an
accumulation of ketone bodies in the blood and urine.
❖ Ketone bodies are acidic and tend to decrease the pH of
the blood.
❖ Lowering of the pH of the blood is called acidosis and
may lead to fatal coma.
❖ During prolonged starvation or on a high-fat, low-
carbohydrate diet, the body tends to burn fat instead of
carbohydrate, leading to ketosis and acidosis.
Lipogenesis vs. Fatty Acid
Degradation
Lipogenesis Degradation of a fatty

acids
Takes place in cell Takes place in
cytosol mitochondrial matrix
Lipid Storage
➢ Fatty acids are stored in adipocytes as triglycerides in
the cells cytoplasm.
➢ When energy is needed, hydrolysis converts TAGs to
fatty acids which are transported to the matrix of
abundant mitochondria where they are oxidized.
➢ Conversion of GLUCOSE to FATS at the
liver and adipose tissue is known to be…
➢ If a person is on high-carbohydrate diet, the rate of lipogenesis

increases
➢ If a person is on a calorie-restricted or high-fat diet or when there is a
deficiency of insulin, the rate of lipogenesis decreases.
➢ The synthesis of fatty acids occurs in the mitochondria and cell
cytoplasm ( synthesis of fatty acid from acetyl CoA)
Fat in excess of the body’s requirement is
stored as ADIPOSE TISSUE.
Stored fat serves as a ;
 RESERVE SUPPLY of FOOD
 SUPPORT FOR THE INTERNAL ORGANS SHOCK
 ABSORBER FOR THE INTERNAL ORGANS
 INSULATOR FOR THE BODY
If more than a normal amount of fat is
deposited in the adipose tissue , the resulting
condition is called ----
a condition resulting from glandular disorder

or simply caused by OVEREATING.
- is found in all cells of the body but
particularly in the brain and
NERVE TISSUE
- all carbon atoms of
cholesterol come from the
acetyl group of acetyl CoA.
- normally eliminated in the bile but
when it settles in the gallbladder,
GALLSTONES are formed
- If it deposits on the walls of

the arteries …
occur
Synthesis:
❖Cholesterol is synthesized primarily in the liver,

but the adrenal cortex, skin, testes, aorta, and
intestines are also able to synthesized it.
❖Synthesis takes place in the microsomal and

cytosomal fraction of the cell
❖Acetyl CoA is a starting material and is also the

source of al the carbon atoms in cholesterol

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Figure 18.

LDL called bad cholesterol because of

• Spiral fatty acid oxidation produce net 95

• 1 Glucose molecule (6 carbon atoms)

3. The liver uses fatty acids as the

4. Brain function is maintained by

▪ Low glucose supply also slows down the citric acid

▪ Under low supply of oxaloacetate the acetyl CoA

▪ As a consequence the excess acetyl CoA is

Formation occurs when the amount of acetyl CoA produced is

– intake is high in lipids and low in carbohydrates.

• Synthesis of ketone bodies from acetyl CoA

❖ In diabetes mellitus the body is unable to oxidize

Lipogenesis Degradation of a fatty

➢ If a person is on high-carbohydrate diet, the rate of lipogenesis

a condition resulting from glandular disorder

- If it deposits on the walls of

❖Cholesterol is synthesized primarily in the liver,

❖Synthesis takes place in the microsomal and

❖Acetyl CoA is a starting material and is also the

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