SIM Biochemistry ULO5

College of Health Sciences Education
3rd Floor, DPT Building

Matina Campus, Davao City
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Big Picture in Focus: ULO5. Demonstrate understanding of lipid

metabolic pathways and its intermediate compounds.
Metalanguage
The most essential terms and concepts below are defined, for you to have a better understanding of this
section in the course. You are advised to frequently refer to these definitions to help you understand the succeeding
topics.
1. Triacylglycerol digestion and absorption – Triacylglycerols are digested (hydrolyzed) in the intestine and then
reassembled after passage into the intestinal wall. Chylomicrons transport the reassembled triacylglycerols from
intestinal cells to the bloodstream.
2. Triacylglycerol storage and mobilization – Triacylglycerols are stored as fat droplets in adipose tissue. When they
are needed for energy, enzyme-controlled hydrolysis reactions liberate the fatty acids, which then enter the
bloodstream and travel to tissues where they are utilized.
3. Glycerol metabolism – Glycerol is first phosphorylated and then oxidized to dihydroxyacetone phosphate, a
glycolysis pathway intermediate. Through glycolysis and the common metabolic pathway, the glycerol can be
converted to CO2 and H2O.
4. Fatty acid degradation – Fatty acid degradation is accomplished through the β-oxidation pathway. The
degradation process involves removal of carbon atoms, two at a time, from the carboxyl end of the fatty acid. There
are four repeating reactions that accompany the removal of each two-carbon unit. A turn of the cycle also produces
one molecule each of acetyl CoA, NADH, and FADH2.
5. Ketone bodies – Acetoacetate, β-hydroxybutyrate, and acetone are known as ketone bodies. Synthesis occurs
mainly in the liver from acetyl CoA as a result of excessive fatty acid degradation. During starvation and in unchecked
diabetes, the level of ketone bodies in the blood becomes very high.
6. Fatty acid biosynthesis – Fatty acid biosynthesis, lipogenesis, occurs through the addition of two-carbon units to
a growing acyl chain. The added two-carbon units come from malonyl CoA. A multi-enzyme complex, an acyl carrier
protein (ACP), and NADPH are important parts of the biosynthesis process.
7. Biosynthesis of cholesterol – Cholesterol is biosynthesized from acetyl CoA in a multistep series of reactions.
Eighteen molecules of acetyl CoA are consumed in the process. Cholesterol is the precursor for the various classes
of steroid hormones.
Reference textbook: Stoker, H. S. (2017). Biochemistry 3rd Edition. C & E Publishing Inc. Quezon City. 1
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Essential Knowledge
Lipid Metabolism
Digestion and Absorption of Lipids
• Dietary Lipids: 98% triacylglycerols (TAGs): Fats and oils

• Salivary enzymes (water soluble) in the mouth have no effect on lipids (TAGs) which are water insoluble.
• In Stomach: most, not all, of TAGs change physically to small globules or droplets -- called chyme which
floats above other material:
• Lipid digestion starts in the stomach:

– Gastric lipase hydrolyzes ester bonds -- 2 fatty acids and one monoacylglycerol --About 10% of TAGS
are hydrolyzed.
o High fat foods stay in stomach for longer time -- high fat meal gives you a feeling of being full
for longer time.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
• Chyme enters into small intestine and is emulsified with bile salts.
• Pancreatic lipase hydrolyzes ester bonds to form fatty acids and glycerol.
– Normally 2 out of 3 fatty acids are hydrolyzed.
• Fatty acids, monoacylglycerols and bile salts make small droplets: called micelles -- hydrophobic chain in
the interior.
• Micelles consist of monoacylglycerols and free fatty acids:
– Small enough to absorb through intestinal cells.
• In the intestinal cells monoacylglycerols and free fatty acids are repackaged to form TAGs.
• These new TAGs combine with membrane lipids (phospholipids and cholesterol) and lipoproteins to form
chylomicrons.
• Chylomicrons transport TAGs from intestinal cells to the bloodstream though the lymphatic system.
• From the lymphatics the fats flow through the thoracic duct into the bloodstream and then to the liver.
• In the liver some of the fats are changed to phospholipids, so the blood leaving the liver contains both fats
and phospholipids.
• These phospholipids, such as sphingomyelin and lecithin are necessary for the formation of nerve and brain
tissues.
• Lecithins are also involved in the transport of fat to the tissues.
• Cephalin, another phospholipid, is involved in the normal blood clotting.
• From the liver, some fat goes to the cells through the bloodstream.
• In the bloodstream TAGs are completely hydrolyzed by lipase enzymes.
• Fatty acids and glycerol are absorbed by the cell and are either broken down to the acetyl Co-A for energy
or repacked to store as lipids.
• The fat in excess of what the cells need is stored in specialized cells called adipocytes (the largest cell in the
body) in the adipose tissue.
– Located primarily beneath the skin especially in abdominal region and vital organs.
– Adipose tissue also serves as a protection against the heat loss and mechanical shock.
• Triacylglycerol energy reserves (fat reserves) are the human body’s major source of stored energy:
– Energy reserves associated with protein, glycogen, and glucose are small to very small when
compared to fat reserves.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Glycerol Metabolism
• Taken to liver or kidney by blood -- converted to dihydroxyacetone phosphate.
• Recall that DHAP is part of the glycolysis pathway.
• This compound may be converted to lactic acid or to glycogen in the liver or muscle tissue or to pyruvic acid,
which enters the TCA cycle.
• Thus, the glycerol part of a fat is metabolized through the carbohydrate sequence.
Oxidation of Fatty Acids

• There are three parts to the process by which fatty acids are broken down to obtain energy.
1. Activation of the fatty acid by binding to Coenzyme-A
• product is called acyl Co-A.
2. Transport of acyl Co-A to mitochondrial matrix.
3. Repeated oxidation (fatty acid spiral) to produce acetyl Co-A, FADH2 and NADH.
• Note: the difference between the designations acyl CoA and acetyl CoA is that acyl refers to a
random-length fatty acid carbon chain that is covalently bonded to coenzyme A, whereas acetyl
refers to a two-carbon chain covalently bonded to coenzyme A.
Fatty Acid Activation and Transport

• Activation of fatty acid takes place in outer mitochondrial membrane.
• FA reacts with coenzyme A at the expense of 2 moles ATP to produce high energy acyl CoA.
• Acyl CoA is too large to pass through the inner mitochondrial membrane to the mitochondrial matrix,
where the enzymes needed for fatty acid oxidation are located; it is converted to acyl carnitine.
• A shuttle mechanism involving the molecule carnitine effects the transport of acyl CoA into the
mitochondrial matrix.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Reactions of the Beta-Oxidation Pathway

• Repeated oxidation of fatty acid, cycling through a series of four reactions to produce acetyl CoA, FADH2,
and NADH.
• The oxidation of fatty acids follow the β-oxidation theory that involves the oxidation of the 2nd carbon atom
from the acid end of the saturated fatty acid molecule, the β-carbon atom.
• In this process, β-oxidation removes two carbon atoms at a time from the fatty acid chain; i.e., an 18-
carbon fatty acid is oxidized to a 16-carbon fatty acid, then to 14-carbon fatty acid, and so on until the
oxidation process is complete.
• The process is also known as fatty acid spiral because the fatty acid goes through the cycle again and again
until it is finally degraded to acetyl CoA.
• The fatty acid spiral is a repetitive series of four reactions (dehydrogenation, hydration, dehydrogenation,
release of acetyl CoA) in which each sequence produces acetyl CoA, FADH2, NADH, and an acyl CoA that is
shorter than the previous acyl CoA by two carbon atoms.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Four Steps of the Beta-Oxidation Pathway
Step 1: Oxidation (dehydrogenation):

• FAD is the oxidizing agent, and a FADH2 molecule is a product.
Step 2: Hydration:
• A molecule of water is added across the trans double bond, producing a secondary alcohol at the beta-
carbon position.
Step 3: Oxidation (dehydrogenation):

• The beta-hydroxyl group is oxidized to a keto functional group with NAD+ serving as the oxidizing agent.
Step 4: Chain Cleavage:

• The fatty acid chain is broken between the alpha and beta carbons by reaction with a coenzyme A molecule.
• The result is an acetyl CoA molecule and a new acyl CoA molecule that is shorter by two carbon atoms than
its predecessor.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
• The acetyl CoA produced enters the citric acid cycle and the new molecule of active fatty acid (active acyl
CoA) goes through the same sequence again, each time losing two carbon atoms until the entire molecule
has been oxidized.
• The sequence presupposes the presence of fatty acids containing an even number of carbon atoms, a
condition usually encountered in nature.
• If fatty acid containing odd number of carbon atoms are oxidized they follow the same steps except that
the final products are acetyl CoA and propionyl CoA. The propionyl CoA is changed in a series of steps to
succinyl CoA, which enters the citric acid cycle, as does the acetyl CoA; these reactions require the presence
of cobamide and biotin.
• The unsaturated fatty acids are metabolized slowly; they must first be reduced by some of the
dehydrogenases found in the cells, then they can follow the fatty acid spiral for oxidation.
• The FADH2 and the NADH + H+ enter the respiratory chain.
ATP Production From Fatty Acid Oxidation
Fatty Acid vs. Glucose Oxidation: A Comparison

• The oxidation of 1 g of fat produces more than twice as much energy as the oxidation of 1 g of
carbohydrate.
• β -oxidation of 18:0 fatty acid (stearic acid) produces a net of 120 ATP molecules.
• 2 ATP molecules are needed for activation of fatty acids so net ATP produced is 120 molecules.
• 1 Glucose molecule (6 carbon atoms) produces 30 ATP molecules.
• Three molecules of glucose (18 Carbon atoms) produce 90 ATP.
• Stearic acid produces 2.5 time more energy than glucose.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Ketone Bodies
• Ordinarily, most of the acetyl CoA produced from the fatty acid spiral is further processed through the Krebs
cycle.
• Therefore an adequate balance in carbohydrate and lipid metabolism is required.
• The first step of the Krebs cycle involves the reaction between oxaloacetate and acetyl CoA; Sufficient
oxaloacetate must be present for the acetyl CoA to react with.
• Oxaloacetate concentration depends on pyruvate produced from glycolysis; pyruvate can be converted
to oxaloacetate by pyruvate carboxylase.
• Certain body conditions upset the lipid-carbohydrate balance required for the acetyl CoA generated by fatty
acids to be processed by the TCA cycle: (under these conditions, the problem of inadequate oxaloacetate
arises).
– Dietary intakes high in fat and low in carbohydrates.
– Diabetic conditions -- glucose not used properly.
– Prolonged fasting conditions.
• When oxaloacetate supplies are too low for all acetyl CoA to be processed through the TCA cycle,
ketogenesis takes place where excess acetyl CoA is converted to ketone bodies.
• Synthesis of ketone bodies from acetyl CoA is primarily in liver mitochondria.
• The three ketone bodies produced are: acetoacetic acid, β-hydroxybutyric acid, and acetone; they are
carried by the blood to the muscles and tissues where they are converted back to acetoacetyl CoA and
then oxidized normally.
• During diabetes, however, the production of ketone bodies by the liver exceeds the ability of the muscles
and tissues to oxidize them so that they accumulate in the blood.
• Ketosis is the overall accumulation of ketone bodies in the blood (ketonemia) and in the urine (ketonuria).
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
• During ketosis acetone may be detected on the patient’s breath because it is a volatile compound and is
easily excreted through the lungs.
• Ketosis may occur with diabetes mellitus, in starvation, or severe liver damage, or on a diet high in fats
and low in carbohydrates.
• During diabetes mellitus, the body is unable to oxidize carbohydrates and instead oxidizes fats, leading to
an accumulation of ketone bodies in the blood and the urine; the ketone bodies are acidic and tend to
decrease the pH of the blood leading to acidosis which may lead to a fatal coma.
• During acidosis, an increased amount of water intake is needed to eliminate the products of metabolism.
Unless the water intake of a diabetic is increased, dehydration will occur. Dehydration of diabetics may
also be caused by polyuria due to an increased amount of glucose in the urine.
• Likewise, during prolonged starvation or on a high-fat, low- carbohydrate diet, the body tends to burn fat
instead of carbohydrates, leading to ketosis and acidosis.
• In severe liver damage, the liver cannot store glycogen in the required amounts so that the carbohydrates
are not available for the normal oxidation of fats, leading to ketosis.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Biosynthesis of Fatty Acids: Lipogenesis
The Citrate–Malate Shuttle System

• Acetyl CoA is the starting material for lipogenesis.
• Acetyl CoA needed for lipogenesis is generated in mitochondria, therefore it must first be transported to
the cytosol.
• Citrate-malate transport system helps transport acetyl CoA to cytosol indirectly.
• Cytoplasmic acetyl CoA is converted to malonyl CoA in a carboxylation reaction that involves CO 2 and ATP.
• The reaction occurs only when cellular ATP levels are high catalyzed by acetyl CoA carboxylase complex,
which requires both Mn2+ and biotin for its activity.
• ACP (Acyl Carrier Protein) Complex Formation:
– All intermediates in fatty acid synthesis are linked to carrier proteins (ACP-SH).
– ACP-SH can be regarded as a “giant CoA-SH molecule”.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Chain Elongation
• Four reactions constitute the steps of chain elongation process
– Condensation: Acetyl-ACP and malonyl-ACP condense together to form acetoacetyl-ACP.
– Hydrogenation: The keto group of the acetoacetyl complex is reduced to alcohol by NADPH.
– Dehydration: Water is removed from alcohol to form an alkene.
– Hydrogenation: Hydrogen is added to alkene 3 to form saturated butyryl ACP from NADPH.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
• In the first “turn” of the fatty acid biosynthetic pathway, acetyl ACP is converted to butyryl ACP. In the
next cycle, the butyryl ACP reacts with another malonyl ACP to produce a 6-carbon acid.
• Continued cycles produce acids with 8, 10, 12, 14, and 16 carbon atoms.
• Elongation of the acyl group chain through this procedure, which is tied to the fatty acid synthase complex,
stops upon formation of the C16 acyl group (palmitic acid).
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Lipogenesis vs. Fatty Acid Degradation
Unsaturated Fatty Acid Biosynthesis and Essential Fatty Acids

• Different enzyme systems and different cellular locations are required for elongation of the chain beyond
C16 and for introduction of double bonds into the acyl group (unsaturated fatty acids).
• Production or unsaturated fatty acids (insertion of double bonds) requires oxidation by molecular oxygen
(O2), which combines with the hydrogen that is removed to form water.
• In humans and animals, enzymes can introduce double bonds only between C 4 and C5 and between C9 and
C10.
• Thus the important unsaturated fatty acids linoleic (C 18 with C9 and C12 double bonds) and linolenic (C18
with C9, C12, and C15 double bonds) cannot be biosynthesized.
• They must be obtained from the diet. Plants have the necessary enzymes to synthesize these acids.
Fate of Fatty-Acid Generated Acetyl CoA

• Acetyl-CoA formed from fatty acids is further channeled in various different routes:
– Oxidation in the citric acid cycle: both lipids and carbohydrates supply acetyl CoA.
– Ketone body formation: Very important when imbalance between carbohydrate and lipid
metabolism.
– Fatty acid biosynthesis: the buildup of excess acetyl CoA when dietary intake exceeds energy needs
energy needs leads to accelerated fatty acid biosynthesis.
– Cholesterol biosynthesis: It occurs when the body is in an acetyl CoA- rich state.
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Cholesterol
• Secondary component of cell membrane.
• Precursor for bile salts, sex hormones and adrenal hormone.
• Body synthesizes 1.5 - 2.0 g of cholesterol every day from acetyl CoA units.
– Average daily dietary intake is ~ 0.3 g
• Synthesis of cholesterol, a C27 molecule, occur in liver and requires at least 15 acetyl CoAs and involves
at least 27 separate enzymatic steps.
• Once cholesterol has been formed, biosynthetic pathways are available to convert it to each of the five
major classes of steroid hormones: progestins, androgens, estrogens, glucocorticoids, and
mineralocorticoids, as well as bile salts and vitamin D.
Overview of Fat and Sugar Synthesis and Breakdown Pathways
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Relationships Between Lipid and Carbohydrate Metabolism

• Acetyl Co-A is the primary link between these two metabolic pathways.
– Acetyl Co-A is the starting material for the biosynthesis of fatty acids, cholesterol and ketone bodies.
– Acetyl CoA is the product of oxidation of glucose, glycerol and fatty acids.
-END-
GOOD JOB!
Telefax: (082)
Phone No.: (082)300-5456/300-0647 Local 117
Keywords Index
Lipid Metabolism Adipocyte Ketone Bodies Acetone
Gastric Lipase Dihydroxyacetone Ketogenesis Acetoacetic Acid
Pancreatic Lipase Carnitine Ketonemia Beta Hydroxybutyric Acid
Micelle Acyl CoA Ketonuria Acyl Carrier Protein
Chylomicron Beta Oxidation Ketosis Lipogenesis

SIM Biochemistry ULO5

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

SIM Biochemistry ULO5

Uploaded by

Copyright:

Available Formats

College of Health Sciences Education

3rd Floor, DPT Building

Big Picture in Focus: ULO5. Demonstrate understanding of lipid

Digestion and Absorption of Lipids

• Dietary Lipids: 98% triacylglycerols (TAGs): Fats and oils

• Lipid digestion starts in the stomach:

Oxidation of Fatty Acids

Fatty Acid Activation and Transport

Reactions of the Beta-Oxidation Pathway

Four Steps of the Beta-Oxidation Pathway

Step 1: Oxidation (dehydrogenation):

Step 3: Oxidation (dehydrogenation):

Step 4: Chain Cleavage:

ATP Production From Fatty Acid Oxidation

Fatty Acid vs. Glucose Oxidation: A Comparison

Biosynthesis of Fatty Acids: Lipogenesis

The Citrate–Malate Shuttle System

Lipogenesis vs. Fatty Acid Degradation

Unsaturated Fatty Acid Biosynthesis and Essential Fatty Acids

Fate of Fatty-Acid Generated Acetyl CoA

Overview of Fat and Sugar Synthesis and Breakdown Pathways

Relationships Between Lipid and Carbohydrate Metabolism

You might also like