Metabolism of Fats

Objectives

Explains the metabolism of lipids & fats.

After the completion of this unit students will
be able to:
1. Describe the mechanism of fatty acid
oxidation
2. Discuss the amount of energy produced
during the oxidation of a fat.
3. Explain the significance of the role of ketone
bodies.
 Introduction

•Reserves of stored triglycerides are mobilized as

needed for energy production.
• Fat mobilization is stimulated by epinephrine. The
triglycerides are hydrolyzed to fatty acids and glycerol and
enter the blood stream.

• Glycerol is converted to glycerol- 3 phosphate and then to

dihydroxyacetone phospahte, which enters glycolysis for
energy production.

• Free fatty acids are converted to fatty acyl CoA molecules,

which are broken down to acetyl CoA by beta oxidation. The
acetyl CoA may be used for energy production by way of the
citric acid cycle and the electron transport chain.
 Fatty acid oxidation
Fatty acids are degraded to acetyl CoA

• Fatty acids enter tissue cells in need of energy. Fatty acids

must pass through the mitochondrial membrane to be
oxidized and to produce energy. The passage cannot occur
until the fatty acid is converted to its thioester with CoA. The
product of this reaction is fatty acyl CoA. The reaction is:
Fatty acid + HS – CoA+ ATP Fatty acyl CoA + AMP + Pi

This is known as activation of fatty acid. Fatty acids must be

activated before they are degraded to produce energy. Fatty
acids are activated in the cytosol, but oxidation occurs in the
mitochondria.
 Beta oxidation
• The formation of fatty acyl CoA molecule prepares fatty acids for
entry into the mitochondria. Carnitine helps fatty acly CoA to
enter mitochondria. There they are degraded in the catabolic
process called beta oxidation. During beta oxidation, the third
(or beta) carbon of the saturated fatty acid chain of the fatty acyl
CoA is oxidized to a ketone.

• Beta oxidation is a spiral pathway. Each round consists of four

enzyme-catalyzed steps that yield one molecule of acetyl CoA
and an acyl CoA shortened by two carbons, which becomes the
starting substrate for the next round. Seven rounds of beta
oxidation degrade a C16 fatty acid to eight molecules of acetyl
CoA.

Complete oxidation of one molecule of palmitic acid to carbon

dioxide and water yields 129 molecules of ATP. One round of
beta oxidation yields 17 ATP.
Beta Oxidation is regulated by availability of free CoA, by the
ratios of NAD/NADH and Q2/QH.
Beta Oxidation Steps
Ketogenesis
Ketogenesis
• Ketogenesis is the biochemical process through
which organisms produce ketone bodies through
breakdown of fatty acids and ketogenic amino acids.
• This process supplies energy under circumstances
such as fasting or caloric restriction to certain
organs, particularly the brain, heart and skeletal
muscle.
• Insufficient gluconeogenesis can cause
hypoglycemia and excessive production of ketone
bodies, ultimately leading to a life-threatening
condition known as ketoacidosis.
• Ketone bodies are produced mainly in the
mitochondria of liver cells, and synthesis can occur
in response to an unavailability of blood glucose,
such as during fasting.
• Other cells are capable of carrying out ketogenesis,
but they are not as effective at doing so.
• Ketogenesis occurs constantly in a healthy
individual.
• Ketogenesis takes place in the setting of low glucose
levels in the blood, after exhaustion of other
cellular carbohydrate stores, such as glycogen.
• It can also take place when there is insufficient
insulin (e.g. in type 1 (but not 2) diabetes)
• The production of ketone bodies is then initiated to
make available energy that is stored as fatty acids.
• Fatty acids are enzymatically broken down in β-
oxidation to form acetyl-CoA. Normally, it enters the
Citric Acid Cycle.
• If activity in TCA cycle is low due to low amounts of
intermediates such as oxaloacetate, acetyl-CoA is
then used instead in biosynthesis of ketone bodies
via acetoacyl-CoA and β-hydroxy-β-methylglutaryl-
CoA (HMG-CoA)
The three ketone bodies, each synthesized from acetyl-CoA
molecules, are:

• Acetoacetate, which can be converted by the liver into β-

hydroxybutyrate, or spontaneously turn into acetone
• Acetone, which is generated through the decarboxylation of
acetoacetate, either spontaneously or through the enzyme
acetoacetate decarboxylase. It can then be further
metabolized either by CYP2E1 into hydroxyacetone (acetol)
and then via propylene glycol to pyruvate, lactate and acetate
(usable for energy) and propionaldehyde, or via
methylglyoxal to pyruvate and lactate.
• β-hydroxybutyrate (not technically a ketone according to
IUPAC nomenclature) is generated through the action of the
enzyme D-β-hydroxybutyrate dehydrogenase on
acetoacetate.
 Ketone Bodies Importance
Health Benefit
1. For around a century ketosis has been used to treat people with epilepsy to
control seizures. (in some, this does not work for all).
2. Ketone bodies can be anti-inflammatory.
3. Long lasting mental benefits, preventing brain fog throughout the day and
keeping stress levels low.
4. Enhanced focus and thought processing.
5. The long-lasting energy that high-fat, low-carb diets provide is valuable for
endurance athletes, sportspeople and those who exercise at length.
6. Fat loss. The fact that low carb dieting leads to the body turning fat into
ketone bodies has the benefit of burning the bodies stored fat.
7. Research indicates that an LCHF diet has the potential to reverse insulin
resistance and possibly type two diabetes. (Under a controlled environment,
overseen by a medical professional).
8. Has a positive impact on blood lipid levels and heart health.
9. Some kinds of cancer cells are unable to use ketone bodies, as they do not
have the necessary enzymes to engage in ketolysis. It has been proposed
that actively engaging in behaviors that promote ketogenesis could help
manage the effects of some cancers.
• Able to manage a variety of Health Problems, including
Obesity
Cardiovascular issues, including issues with
cholesterol
Neurological issues, including stroke-based
damage
Type 2 diabetes
Alzheimer's disease
Various types of cancer
Disadvantages
• Individuals with diabetes mellitus can experience overproduction of
ketone bodies due to a lack of insulin.
• Without insulin to help extract glucose from the blood, tissues the
levels of malonyl-CoA are reduced, and it becomes easier for fatty
acids to be transported into mitochondria, causing the accumulation
of excess acetyl-CoA.
• The accumulation of acetyl-CoA in turn produces excess ketone
bodies through ketogenesis.
• The result is a rate of ketone production higher than the rate of
ketone disposal, and a decrease in blood pH.