FAT CATABOLISM - the process by which fats are broken
down in our bodies through enzymes and
Triacylglycerols (TAGs) - a major form of energy
storage in animals
- 3 fatty acids that bind in glycerol
Your energy reserves:
- 0.5% carbs (glycogen + glucose)
- 15% protein (muscle, last resort): most
important
- 85% fat
WHY USE FAT FOR ENERGY?
1 gram fat = at least 6-fold more energy than 1
gram carb
1 gram = 9 kcal
Sources of fat:
1. Diet
2. Stored fat (adipose tissue)
3. Fat synthesized in one organ for export to
another (excess carb converted to fat)
When the level of glycogen is decreased, the rate
of fats is increasing for degradation. The glycogen
is prioritized to a breakdown in times of starvation
and then fats are second.
OVERVIEW OF LIPID CATABOLISM
● Triglycerides account for ~83% to 85% of
our stored energy
● Mobilized slower than carbs and ​only
aerobically
● Principal fuel for many organs (e.g., heart,
liver)
In normal time, the brain is consumed only
glucose. But the heart and liver are
utilized only fatty acids. But in times of
starvation, the brain is not really function.
● More energy per gram than carbs (9 kcal
vs. 4)
LIPOLYSIS - hydrolysis of fat/digestion of
fat/breakdown of fat
SEARCH: LIPOLYSIS
- the metabolic pathway through which lipid
triglycerides are hydrolyzed into glycerol
and three fatty acids. It is used to mobilize
stored energy during fasting or exercise
and usually occurs in fat adipocytes.
water, or hydrolysis. Lipolysis occurs in
our adipose tissue stores, which are the
fatty tissues that cushion and line our
bodies and organs. In fact, fats can be
thought of simply as stored energy.
TRANSPORT OF LIPIDS
● Nonpolar lipids need to be escorted
through the bloodstream via lipoprotein
complexes.
- Chylomicrons carry dietary lipids to
tissues
- VLDLs carry lipids synthesized in
the liver to tissues
- LDLs carry cholesterol to tissues
- HDLs carry cholesterol to the liver
from tissues; cleanser
ABSORPTION OF DIETARY FATS
● Dietary lipids must be emulsified and
packaged for transport in the bloodstream
- Bile salts are made from
cholesterol in the liver; stored in
the gall bladder
NOTE: Taurocholic acid - the semi-essential
component of this is taurine, one of the
precursors of bile salt.
FAT CATABOLISM
HOW ARE FATTY ACIDS BURNED FOR
ENERGY?
1. Transported to mitochondria, after lipolysis
2. Oxidized to produce acetyl CoA, NADH,
FADH2
3. Acetyl CoA goes to the citric acid cycle NADH,
FADH2 donates an electron to oxidative
phosphorylation (ETC)
MOBILIZATION OF FAT STORES
● Hormone (glucagon or epinephrine -
catabolic hormones) binds to fat cell
(adipocyte) receptor, activating protein
kinase A: the target is an adipocyte (when
fat is release in this site it becomes free
fatty acids and goes to the bloodstream)
When the level of these hormones rises in the
blood then the catabolic mode of metabolism
would be activated.
● Phosphorylation activates lipase and
perilipin, triggering the release of fatty
acids
FATE OF TRIGLYCERIDE PRODUCTS
GLYCEROL - enters the dihydroxyacetone
phosphate of G3P
The enzymes are involved in step 5. Therefore,
the ​glycerol turns to glycolysis​.
MATRIX IN MITOCHONDRION
- Beta-oxidation pathway in the matrix.
ACTIVATION OF FATTY ACIDS BY COA
A CoA molecule is added to the fatty acid to
produce acyl-CoA, converting ATP to AMP in the
process.
Note that in this step, the ATP is converted to
AMP, not ADP. Thus, activation uses the
equivalent of 2 ATP molecules.
The enzyme fatty acyl-CoA synthetase forms
AMP fatty acids or Fatty acyl-adenylate
(enzyme-bound) - it combines fat molecules and
AMP
There is an enzyme that produces the final
product of the activation of FA is called fatty
acyl-CoA synthetase. It removes the AMP and the
molecules of CoA are combined so it produced
Fatty acyl-CoA.
FATTY ACYL-COA is activated of FA
WHY do WE need TO ACTIVATE THE FA?
To enter the mitochondrion matrix.
ROLE OF CARNITINE
- Is to carry/transport the activated fatty acid
into the matrix
- The carnitine shuttle represents a
mechanism by which long-chain fatty
acids, which are impermeable to the
mitochondrial membranes, are transported
into the mitochondrial matrix for the
purpose of β-oxidation and energy
production
- When carnitine is entered in the matrix,
the carnitine is regenerated - releasing the
fatty acids and then FA is reformed by
adding CoA molecule.
 OVERVIEW OF BETA-OXIDATION
✦ Fatty acids are broken down 2-carbon units at
a time, starting at the carboxyl end.
✦ Pieces are released as acetyl-CoA.

So when activated the FA, the palmitic acid turns

to palmitoyl-CoA and so on.

REACTION STAGES
REACTION 1: OXIDATION REACTION 4: THIOLYTIC CLEAVAGE
Three isozymes of acyl-CoA dehydrogenase: This stage involved half twice the FA to form
Long-chain (14-18C) Acetyl-CoA and there is another CoA added to
Medium (8-14C) the terminal end to sustain the Acetyl-CoA
Short (4-6C) production.
FAD is produced FADH2
Production: Trans-delta-Enoyl-CoA
Enzyme: acyl-CoA dehydrogenase

REACTION 2: HYDRATION
From Trans-delta-Enoyl-CoA converts to
L-beta-hydroxy acyl-CoA by the enzymes
enoyl-CoA hydratase and added by water

Example: 16 carbons divided by 2 = 8 so 8

acetyl-CoA produced but 7th times cleave/runs.
So, therefore, there are 7 NADH produce and &
FAH2

OXIDATION OF UNSATURATED FATS

● Double bonds are always cis.
REACTION 3: OXIDATION
● The process is stopped first and then the
Beta-ketoacyl-CoA produced by B-hydroxy
isomerase is needed to ​convert the cis
acyl-CoA dehydrogenase and then reduction of
​ ppropriate trans
double bond​ to the a
NAD+ to formed NADH
intermediate​. And then continue the
process in beta-oxidation until completely
cleaved the unsaturated fatty acids

POLYUNSATURATED FATS
● The same process in monounsaturated
fatty acids. Convert first the double bond
cis into trans and then continue the
process until it’s cleaved completely the
FA.
REMEMBER: Some polyunsaturated fats are
“essential” building blocks for signaling molecules
such as prostaglandins, thromboxanes, and
leukotrienes.
A high fish diet correlates to lower acute MI
(sudden heart attack) rates. YES. Fish is high in
omega-3 and low in omega-6. So high fish diet
correlates to lower heart attack rates because
due to EPA and DHA content as well as the
anti-inflammatory effects of omega-3.
What do EPA and DHA due to lower the risk for
heart disease?
- Lower heart rate
- Prevent ventricular tachyarrhythmias
- Lower blood pressure
- Lower platelet function
KETONE BODIES
● Ketogenesis - formation of ketone bodies
or simple ketones
- Ketones formed from FA
- Ketones formed when the energy
is deficit (e.g. starvation, fasting)
- Ketones formed when the
carbohydrates are not enough in
our body.
● Made in the mitochondrial matrix of only in
the liver cells (hepatocyte).
- In the kidney also occurred
ketogenesis but at a small rate.
LIPID METABOLISM
KETONE BODIES
In the liver, some acetyl CoA is exported to blood
as “ketone bodies” for use in other tissues, rather
than burned in the liver by the citric acid cycle

OXIDATION OF ODD-CHAIN FATS

● Propionyl-CoA (3 carbon) is the last piece
released (products if the FA is odd-chain)
● Propionyl-CoA undergoes conversion to WHY THERE IS NEED TO PRODUCED
succinyl-CoA, which enters TCA.
KETONE?
● Vitamins involved:
Because during starvation/energy deficit it is
- Biotin is a coenzyme that needs
depleted TCA intermediates, diverting acetyl CoA
the enzyme Propionyl-CoA
to ketone body production. Instead of continuing
carboxylase. the TCA cycle, there are actually converted to
- Vitamin B12 is a coenzyme that
glucose in the process called gluconeogenesis
needs the enzyme
that happens when starvation.
methyl-malonyl-CoA mutase
SEARCH: Ketones and ketoacids are alternative
VITAMIN B12 - Dorothy Crowfoot Hodgkin fuels for the body that are made when glucose is
(1910-1994): Nobel prize winners of 1964
in short supply. They are made in the liver from
the breakdown of fats. Ketones are formed when
there is not enough sugar or glucose to supply
VERY LONG OR BRANCHED CHAIN
the body's fuel needs. This occurs overnight, and
● Found in shellfish or marine foods. during dieting or fasting.
● Predominantly in the peroxisomes.
NOTE: Peroxisomes in the oxidation of very long
WHY GLUCOSE IS EASY TO lose?
FA Because glucose is demand in our brain.
● Defects can lead to serious diseases such
as X-linked Adrenoleukodystrophy
(genetic disease)
HOW TO MAINTAIN THE TCA CYCLE DURING DIABETIC KETOACIDOSIS
STARVATION?
SEARCH: The plasma levels of fatty acids and
ketone bodies increase in starvation, whereas
that of glucose decreases. The metabolic
changes on the first day of starvation are like
those after an overnight fast. The low blood-sugar
level leads to ​decreased secretion of insulin
and ​increased secretion of glucagon​.

KETONE BODIES:
- Soluble, transportable
- Reconverted back to acetyl CoA in other - Medical emergency. It happens in patient
tissues with Diabetic Type 1
- Fuel for heart muscle Major fuel for brain - Very rare
(starvation)
- It happens if grabe ang starvation
- There are three: acetoacetate, - 3 to 2 days starvation, the source of
β-hydroxybutyrate, and acetone (release energy is ketones as well in the brain and
through exhalation) liver
- NORMAL KETOSIS CALLED
PHYSIOLOGIC KETOSIS

ALCOHOLIC KETOACIDOSIS
- Occur in alcoholic individuals

KETOLYSIS - breakdown of ketones for energy

HOW TO PRODUCE KETOGENESIS?

1. Acetyl-CoA is condensed formed into 2
and forming acetoacetyl-CoA (4 carbon)
2. Acetoacetyl-CoA formed HMG-CoA by the
enzyme of HMG-CoA synthase.
When β-hydroxybutyrate converted to
3. HMG-CoA formed acetoacetate by the
acetoacetate there are reduction of NAD into
enzyme HMG-CoA lyase cleaving an
NADH and fed to ETC
acetyl-CoA molecule
4. Acetoacetate converted to either
GLUCOGEONESIS - occurred in liver not in
β-hydroxybutyrate (β-hydroxybutyrate
muscle. Most gluconeogenesis (about 90%)
dehydrogenase) - preferred because it
happens in the liver, and the remaining 10%
used in energy or acetone (Acetoacetate
occurs in the kidney. In particular, three crucial
decarboxylase) - exhale.
irreversible steps occur in gluconeogenesis

HOW TO USE KETONES IN ENERGY?

All enzymes that involved in producing Ketones
Acetoacetate and β-hydroxybutyrate are fed into
bodies is all in LIVER.
the TCA cycle
KETONES HIGH IN DIABETES KETOACIDOSIS
- The presence of high levels of ketones in
the bloodstream is a common
complication of diabetes, which if left
untreated can lead to ketoacidosis.
Ketones build up when there is insufficient
insulin to help fuel the body's cells
- Without enough insulin, your body can't
use sugar properly for energy. This
prompts the release of hormones that
break down fat as fuel, which produces
acids known as ketones. Excess ketones
build up in the blood and eventually "spill
over" into the urine.