Lipid Metabolism
Extreme diets that are
Refers to the breakdown and synthesis of fats.
Dietary fats are digested mainly in the small intestines
through the action of bile salts and pancreatic lipase
Bile salts emulsify fats. They act as a detergent,
breaking large globules of fat into smaller micelles,
making them more accessible to lipase. Pancreatic
Lipase then converts triglycerides into
monoglycerides, free fatty acids, and glycerol. These
products move into the cells of intestinal epithelium –
the enterocytes, inside which they re-combine again to
form triglycerides. Triglycerides are packaged along
with cholesterol into large lipoprotein particles called
Chylomicrons. Lipoproteins enable transport of
water-insoluble fats within aqueous environments.
Chylomicrons leave the enterocytes, enter lymphatic
capillaries, and eventually pass into the bloodstream,
delivering fats to tissues. The walls of blood capillaries
have a surface enzyme called Lipoprotein Lipase.
This enzyme 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,
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 Metabolism pathways are closely
connected to those of carbohydrate metabolism.
Glycerol is converted to a glycolysis intermediate,
while fatty acids undergo beta-oxidation to generate
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 election
transport system.
Fats yield more energy per unit mass than
carbohydrates. When acetyl-CoA is produced in
excess, it is diverted to create ketone bodies. 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 in a serious complication of
diabetes, in which cells must oxidize fats for fuel as
they cannot utilize glucose.
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.
Lipid digestion and absorption
Lipids are large molecules and generally are
not water-soluble. Like carbohydrates and protein,
lipids are broken into small components for absorption.
Since most of our digestive enzymes are water-based,
how does the body break down fat and make it
available for the various functions it must perform in
the human body?
From the Mouth to the Stomach
The first step in the digestion of triglycerides
and phospholipids begins in the mouth as lipids
encounter saliva. Next, the physical action of chewing
coupled with the action of emulsifiers enables the
digestive enzymes to do their tasks. The enzyme
lingual lipase (It breaks medium and long-chain
triacylglycerols or fats into smaller bits), along with a
small amount of phospholipid as an emulsifier,
initiates the process of digestion. These actions cause
the fats to become more accessible to the digestive
enzymes. As a result, the fats become tiny droplets and
separate from the watery components.
From the Mouth to the Stomach
In the stomach, gastric lipase starts to break
down triglycerides into diglycerides and fatty acids.
Within two to four hours after eating a meal,
roughly 30 percent of the triglycerides are converted to
diglycerides and fatty acids.
The stomach’s churning and contractions help
to disperse the fat molecules, while the diglycerides
derived in this process act as further emulsifiers.
However, even amid all of this activity, very little fat
digestion occurs in the stomach.
Emulsification (of lipids) - a process in which
large lipid globules are broken down into several
small lipid globules.
TO THE BLOODSTREAM WE GO!!!!!
Going to the Bloodstream
As stomach contents enter the small intestine,
the digestive system sets out to manage a small
obstacle, namely, to combine the separated fats with its
own watery fluids.
The solution to this obstacle is bile. Bile contains bile
salts, lecithin, and substances derived from cholesterol,
so it acts as an emulsifier. It attracts and holds onto fat
while it is simultaneously attracted to and held on to by
water.
Emulsification increases the surface area of lipids over
a thousand-fold, making them more accessible to the
digestive enzymes.
NOTE:
In this stage, emulsification becomes anabolic (see
previous definition of emulsification)
Once the stomach contents have been emulsified, fat-
breaking enzymes work on the triglycerides and
diglycerides to sever fatty acids from their glycerol
foundations.
As pancreatic lipase enters the small intestine, it breaks
down the fats into free fatty acids and monoglycerides.
Bile salts envelop the fatty acids and monoglycerides
to form micelles. Micelles have a fatty acid core with a
water-soluble exterior.
This allows efficient transportation to the intestinal
microvillus. Here, the fat components are released and
disseminated into the cells of the digestive tract lining.
Intestinal Cells to Bloodstream
Inside the intestinal cells, the monoglycerides and fatty
acids reassemble themselves into triglycerides.
Triglycerides, cholesterol, and phospholipids form
lipoproteins when joined with a protein carrier.
Lipoproteins have an inner core that is primarily made
up of triglycerides and cholesterol esters (a cholesterol
ester is a cholesterol linked to a fatty acid). The outer
envelope is made of phospholipids interspersed with
proteins and cholesterol.
Together they form a chylomicron, which is a large
lipoprotein that now enters the lymphatic system and
will soon be released into the bloodstream via the
jugular vein in the neck. Chylomicrons transport food
fats perfectly through the body’s water-based
environment to specific destinations such as the liver
and other body tissues.
Protein Metabolism
Proteins are responsible for nearly all bodily
and cellular functions: from structural proteins in
bones; contractile proteins in muscles; transport
proteins in blood plasma; to hormones, antibodies, cell
receptors, ion channels, and enzymes that catalyze
almost every chemical reactions in biological systems.
Proteins are polymers of amino acids linked
together by peptide bonds. AN amino acid consists of
an amino group, a carboxyl group, and a unique side
chain, connected to a central carbon, the α-carbon.
Instead of being an extended of chain of amino acids, a
protein usually folds into a three-dimensional
confirmation that is critical for its functions. The
structure forms as a result of interactions between the
side chains of amino acids and is thus dictated by the
amino acid sequence.
Of the 20 amino acids that make up proteins,
nearly half are essential, meaning the body cannot
synthesize them and must get them from the diet.
Animal proteins are usually considered high quality,
complete proteins, because they have similar amino
acid composition as human proteins, and can thus
provide all the required amino acids, but a combination
of a variety of plant foods may also do the job.
Proteins in foods are digested in the stomach
and small intestine, by the action of stomach acid,
which denatures proteins, and several enzymes that
hydrolyze peptide bonds. Together they break down
proteins into individual amino acids, which are then
absorbed into the bloodstream and transported to the
liver. The liver uses these amoino acids to synthesize
new proteins, most of which are plasma proteins. The
liver also distributes free amino acids to other tissues,
for synthesis of tissue-specific proteins. Proteins are
synthesized based on genetic information of the cell,
using the genetic code, and regulatory signals.
Each cell has a characteristic collection of
proteins, specific to its functions. Body proteins are
constantly renewed. Older proteins are broken down
into free amino acids which are recycled, they combine
with dietary amino acids to make new proteins.
Unlike carbohydrates and lipids, proteins
cannot be stored for later use. Once the cellular
requirement for proteins in met, excess amino acids are
degraded and used for energy, or converted into
glucose of fatty acids.
 Use of amino acids for energy production also
occurs when there is energy shortage, such as during
prolonged exercise or extended fasting. Since there are
no nitrogenous compounds in the energy production
pathways, the first step in amino acid degradation is
the removal of the amino group, by deamination of
transamination, to produce keto-acids.
Some amino acids can be directly deaminated,
while others must transfer their amino group to α-
ketoglutarate to form glutamate, which is then
deaminated to recycle α-ketoglutarate.
Depending on their side chains, keto-acids
from different amino acids may enter the metabolic
cycles at different points. They may be converted to
pyruvate, acetyl-CoA, or one of the intermediates of
the citric acid cycle. Some of these reactions are
reversible.
When amino acids are in short supply, citric
acid intermediates can be aminated to create new
amino acids for protein synthesis.
Deamination produces ammonia, which is
toxic if accumulated. The liver converts ammonia to
urea to be excreted in urine. Extreme diets that are
excessively high in proteins may overwhelm the
kidneys with nitrogenous waste and cause renal
damage.
Protein Digestion and absorption
How are proteins digested and absorbed by our bodies?
Let’s follow the specific path that proteins take down
the gastrointestinal tract and into the circulatory
system. We will use an egg as our example to describe
the path of proteins in the process of digestion and
absorption. Eggs are very rich in protein.
The first step in egg digestion (or any other protein
food) involves chewing. The teeth begin the
mechanical breakdown of the large egg pieces into
smaller pieces that can be swallowed.
The SALIVARY GLANDS provide some saliva to aid
swallowing and the passage of the partially mashed
egg through the esophagus. The mashed egg pieces
enter the stomach through the esophageal sphincter.
How are proteins digested and absorbed by our bodies?
The stomach (Gastric Glands) releases gastric juices
containing hydrochloric acid and the enzyme, pepsin,
which initiate the breakdown of the protein.
The acidity of the stomach facilitates the unfolding of
the proteins that still retain part of their three-
dimensional structure after cooking and helps break
down the protein aggregates formed during cooking.
(Remember Denaturation – Folded to unfolded state of
protein)
Pepsin, which is secreted by the CHIEF CELLS that
line the stomach, dismantles the protein chains into
smaller and smaller fragments. Egg proteins are large
globular molecules, and their chemical breakdown
requires time and mixing. The powerful mechanical
stomach contractions churn the partially digested
protein into a more uniform mixture called chyme.
Protein digestion in the stomach takes a longer time
than carbohydrate digestion, but a shorter time than fat
digestion. Eating a high-protein meal increases the
amount of time required to sufficiently break down the
meal in the stomach. Food remains in the stomach
longer, making you feel full longer.
From the Stomach to the Small Intestine
The stomach empties the chyme containing the
broken-down egg pieces into the small intestine, where
the majority of protein digestion occurs.
The pancreas secretes digestive juice that contains
more enzymes that further break down the protein
fragments. The two major pancreatic enzymes that
digest proteins are chymotrypsin and trypsin.
The cells that line the small intestine release additional
enzymes that finally break apart the smaller protein
fragments into the individual amino acids.
The process through which proteins are broken down
into smaller polypeptide chains or amino acids is
called proteolysis. The process is catalyzed by
enzymes called proteases.
The muscle contractions of the small intestine mix and
propel the digested proteins to the absorption sites. The
goal of the digestive process is to break the protein into
dipeptides and amino acids for absorption.
The process through which proteins are broken down
into smaller polypeptide chains or amino acids is
called proteolysis. The process is catalyzed by
enzymes called proteases (peptidase or proteinase)
In the lower parts of the small intestine, the amino
acids are transported from the intestinal lumen through
the intestinal cells to the blood. This movement of
individual amino acids requires Sodium Co-transporter
and the cellular energy molecule, adenosine
triphosphate (ATP).
Amino acids and dipeptides enters the enterocyte then
transported to the bloodstream. Dipeptides are further
broken down by cytoplasmic peptidases and exported
from the cell into blood.
Ketone Bodies
Ketone bodies are 3 chemicals thar are
produced in the body during fasting or starvation to
meet the body’s energy needs. The three ketone bodies
are: acetone, acetoacetate, and 3-Hydroxybutyrate
(which is the most abundant one).
What triggers ketogenesis during fasting?
- Insulin levels drop
- Glucagon level increases
Glucagon acts on adipose tissues to cause lipolysis
which releases plenty of free fatty acids into the blood.
These free fatty acids are clariid to the liver where they
undergo beta-oxidation, producing large amounts of
acetyl-CoA.
When the concentration of acetyl-CoA produced
from beta-oxidation exceeds the oxidative capacity of
GCA Cycle, Acetyl-CoA is directed towards
ketogenesis.
Apart from free fatty acids, acetyl-CoA can also be
generated from ketogenic amino acids
Process of Ketogenesis
Ketogenesis is the formation of ketone bodies
which occurs in the liver as it has the enzyme HMG-
CoA Lyase, which is the most important enzyme
required in ketogenesis.
Firstly, two acetyl-CoA molecules combine to
form acetoacetyl-CoA in which another acetyl-CoA is
added into the enzyme HMG-CoA Synthase then
HMG-CoA is produced.
HMG-CoA is then acted upon by HMG-CoA
Lyase into acetoacetate and acetyl-CoA. While some
of the acetoacetate is converted spontaneously into
acetone, the rest of them (or larger amount of them) is
converted into 3-Hydroxybutyrate through the enzyme
3-Hydroxybutyrate dehydrogenase. This reaction is
reversible
Ketolysis
Ketolysis is the breakdown of acetoacetate and
3-hydroxybutyrate in peripheral tissues, such as
muscle, brain, etc. to convert them back into two
molecules of acetyl-CoA. Firstly, acetoacetate and 3-
hydroxybutyrate are brought to the peripheral tissues.
3-Hydroxybutyrate is oxidized to acetoacetate by the
same enzyme 3-hydroxybutyrate dehydrogenase which
also produces NADH. Acetoacetate now acquires
Coenzyme A from Succinyl Coenzyme A of the TCA
Cycle and through the enzyme Thiophorase, it converts
into Acetoacetyl CoA.
Note that Thiophorase enzyme is not present
in the liver, so liver is not capable of conducting
ketolysis.
Acetoacetyl CoA is actively removed by its
conversion into two molecules of Acetyl-CoA and
thus, ketolysis is completed
Terminologies
 Rate of ketone body production is greater than
their use. Their levels begin to rise in the blood,
which is termed as Ketonemia, and in the urine,
which is termed as Ketonuria.
 When there is ketonemia, ketonuria, and smell of
acetone in breath, such condition is termed as
Ketosis, which is diagnosed by a special test called
Rhothera’s test
 In patients with Type 1 diabetes, Ketonemia and
Ketonuria is often seen. In these patients, increased
level of glucagon leads to lipolysis which increases
free fatty acids in plasma and ultimately increases
hepatic output of ketone bodies which leads to
Diabetic Ketoacidosis – which is basically the rise
of ketone bodies in the blood to a toxic level
 Ketoacidosis is also seen in prolonged fasting
and excessive ethanol consumption
Ketone bodies are chemicals that the body makes when
there is not enough insulin in the blood, and it must
break down fat instead of the sugar glucose for energy
(Shiel, 2016). Ketones are substances produced by the
liver during gluconeogenesis, a process that creates
glucose in times of fasting and starvation.
Ketosis, Acidosis and Dehydration
Ketosis - a process that happens when your body
doesn't have enough carbohydrates to burn for energy.
Instead, it burns fat and makes things called ketones,
which it can use for fuel. There are benefits and side
effects when the body has undergone ketosis as listed.
Acidosis - a condition in which there is too much acid
in the body fluids. caused by an overproduction of acid
that builds up in the blood or an excessive loss of
bicarbonate from the blood (metabolic acidosis) or by
a buildup of carbon dioxide in the blood.
The type of acidosis is categorized as either respiratory
acidosis or metabolic acidosis, depending on the
primary cause of your acidosis.
Respiratory acidosis occurs when too much CO2
builds up in the body. Normally, the lungs remove
CO2 while you breathe. However, sometimes your
body can’t get rid of enough CO2. This may happen
due to chronic airway conditions, like asthma injury to
the chest obesity, which can make breathing difficult,
sedative misuse, overuse of alcohol, muscle
weakness in the chest, problems with the nervous
system, deformed chest structure
Metabolic acidosis starts in the kidneys instead of the
lungs. It occurs when they can’t eliminate enough acid
or when they get rid of too much base. There are three
major forms of metabolic acidosis.
Diabetic acidosis occurs in people with diabetes that’s
poorly controlled. If your body lacks enough insulin,
ketones build up in your body and acidify your blood.
Hyperchloremic acidosis results from a loss of sodium
bicarbonate. This base helps to keep the blood neutral.
Both diarrhea and vomiting can cause this type of
acidosis.
Lactic acidosis occurs when there’s too much lactic
acid in your body. Causes can include chronic alcohol
use, heart failure, cancer, seizures, liver failure,
prolonged lack of oxygen, and low blood sugar. Even
prolonged exercise can lead to lactic acid buildup.
Renal tubular acidosis occurs when the kidneys are
unable to excrete acids into the urine. This causes the
blood to become acidic.
QUIZ
1. A type of acidosis that occurs when two much
CO2 builds up in the body. Respiratory Acidosis
2. Among the types of ketone bodies which is being
created from the breakdown of fatty acids.
Acetoacetate
3. The following are positive signs when you are in
ketonic except. (Positive = Sustained fat loss,
Clearer Cognition, and more stable energy | Except
= Clearer Skin)
4. This emulsifier is produced in the liver and stored
in the gall bladder and will be released in the small
intestine once needed. Bile
5. This metabolic acidosis occurs when kidneys are
unable to excrete acids into the urine. Renal
Tubular Acidosis
6. This process occurs when the body do not have
enough carbohydrates to burn for energy and burns
fats instead. Ketosis
7. These substances are being produced by the liver
during gluconeogenesis. Ketone Bodies
8. This type of ketone bodies is considered as one in
the ketogenic diet and formed from acetoacetate.
Beta-Hydroxybutyric Acid
9. What chemicals does the body make when there is
not enough insulin. Ketone Bodies
10. What condition starts in the kidneys instead of
the lungs which occurs when it cannot eliminate
enough acid or too much taste? Metabolic Acidosis
11. What is the orientation of micelle that carries oil?
Normal Micelle
12. What is the orientation of micelle that carries
water? Reverse Micelle
13. What will be formed when triglycerides,
cholesterol and phospholipid joined with a protein
carrier? Lipoprotein
14. Where does monoglycerides and fatty acids
reassemble into triglycerides. Intestinal Cells
15. Which allows the lipids to diffuse into the mucosal
cells? Microvilli
16. Which compounds were used to provide energy to
the cells of the body when glucose is low or absent
in the diet? Ketone Bodies
17. Which condition occurs when there is too much
acid in the body fluids? Acidosis
18. Which enzyme is released in the small intestine to
breakdown fats into free fatty acids and
monoglycerides? Pancreatic Lipase
19. Which has a fatty acid core with a water-soluble
exterior? Micelle
20. Which of the following enzymes break medium
and long chain triaglycerols or fats into small bits?
Lingual Lipase
21. Which substance causes the fats to become more
accessible to the digestive enzymes? Emulsifier
22. Which type of ketone bodies is created as a side
product of acetoacetate that breaks down quickly
and is removed from the body through breath.
Acetone
23. Which type of metabolic acidosis causes chronic
alcohol use and heart failure? Lactic Acidosis
24. Which type of metabolic acidosis results from a
loss sodium bicarbonate? Hyperchloremic
Acidosis
25. Which type of metabolic acidosis results from too
much lactic acid in your body? Lactic Acidosis