![Page 1: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/1.jpg)
Metabolism of lipids
Dr. Mamoun AhramBiochemistry for Nursing
Summer 2015
![Page 2: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/2.jpg)
Sources of lipids
• They enter the pathways – from the digestive tract as food is broken down, – from adipose tissue, where excess lipids have been
stored• fatty acids released from adipose tissue associate with
albumin and are transported to other tissues– from the liver, where lipids are synthesized.
![Page 3: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/3.jpg)
Digestion of triglycerides
![Page 4: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/4.jpg)
Why do we fell full when we eat fatty food?
• The presence of triacylglycerols in consumed food slows down the rate at which the mixture of partially digested foods leaves the stomach
![Page 5: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/5.jpg)
Digestion of triglycerides
• Lipases are released from pancreas.
• Bile is released from gallbladder to emulsify lipids– Cholic acid is the major
bile
![Page 6: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/6.jpg)
Cholic acid (just like soap)
Bile acids are derived from cholesterol
![Page 7: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/7.jpg)
Pancreatic lipase
![Page 8: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/8.jpg)
Interstitial villi
![Page 9: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/9.jpg)
Lacteal (lymphatic vessel)
![Page 10: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/10.jpg)
Lipid absorption
• Small fatty acids and glycerol are water-soluble and are absorbed directly through the surface of the villi.
• The water-insoluble acylglycerols and larger fatty acids are released from the micelles at the intestinal lining and absorbed.
![Page 11: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/11.jpg)
Lipoproteins
Because lipids are less dense than proteins, the density of lipoproteins depends on their ratio of lipids to proteins.
Therefore, lipoproteins can be divided into five major types distinguishable by their composition and densities.
![Page 12: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/12.jpg)
Transport of lipids
back to the liver, where it is converted to bile acids.
to peripheral
tissues
![Page 13: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/13.jpg)
Chylomicrons
• Chylomicrons are too large to enter the bloodstream through capillary walls.
• Instead, they are absorbed into the lymphatic system through lacteals within the villi and are carried to the thoracic duct where the lymphatic system empties into the bloodstream.
• These are the lowest-density lipoproteins because they carry the highest ratio of lipids to proteins.
![Page 14: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/14.jpg)
Good versus bad cholesterol
• LDL (the so-called bad cholesterol) delivers more cholesterol than is needed to peripheral tissues– if not enough HDL (the so-called good cholesterol) is
present to remove it, the excess cholesterol is deposited in cells and arteries.
• LDL also can trigger inflammation and the buildup of plaque in artery walls.
![Page 15: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/15.jpg)
Lipoprotein lipase (LPL)
• TAGs in chylomicrons are hydrolyzed in the bloodstream by lipoprotein lipases that are anchored in capillary walls.
• The resulting fatty acids have two possible fates:
(1)When energy is in good supply, they are converted back to TAGs for storage in adipose tissue.
(2)(2) When cells need energy, the fatty acid carbon atoms are oxidized into acetyl-SCoA.
![Page 16: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/16.jpg)
![Page 17: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/17.jpg)
Fate of fatty acidsHydrolysis/
mobilization
For storageIn adiposetissues
Lipogenesis
Steroids
Ketogenesis
Protein metabolism
![Page 18: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/18.jpg)
Lipases of adipocytes
Inhibited by insulinActivated by glucagon
• When energy is needed, lipases within fat cells are activated by hormones (insulin and glucagon).
• The stored TAGs are hydrolyzed to fatty acids, and the free fatty acids and glycerol are released into
• the bloodstream. • The fatty acids travel in association with albumins
to cells where they are converted to acetyl-CoA for energy generation.
![Page 19: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/19.jpg)
Glycerol
Links lipid and carbohydrate metabolism
The glycerol produced from TAG hydrolysis is carried in the bloodstream to theliver or kidneys, where it is converted to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP)
Adipocytes do not have the kinase needed to convert glycerol to glycerol 3-phosphate, they cannot synthesize triacylglycerols
![Page 20: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/20.jpg)
Leptin and grehlin
• Leptin, a peptide hormone, is synthesized in adipocytes and acts on the brain to stop eating it suppresses appetite.
• Grehlin, another peptide hormone, stimulates intense sensations of hunger.
![Page 21: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/21.jpg)
Synthesis of triacylglycerols
After a meal, blood glucose levels increase rapidly, insulin levels rise, and glucagon levels drop. Glucose enters cells, and the rate of glycolysis increases. Under these conditions, insulin activates the synthesis of TAGs forstorage.
The basic phospholipid
![Page 22: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/22.jpg)
Oxidation of fatty acids
• The purpose is to produce coenzymes (NADH and FADH2) that will enter the elelctron transport chain and produce ATP.
• This is done in four stages:– Activation– Transport– Beta-oxidation
![Page 23: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/23.jpg)
Activation of fatty acid
• The fatty acid must be activated by conversion to fatty acyl-SCoA.
• This activation, which occurs in the cytosol.• ATP is consumed.
![Page 24: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/24.jpg)
Transport into mitochondrial matrix
• The fatty acyl-SCoA cannot cross the mitochondrial membrane by diffusion and must be transported from the cytosol into the mitochondrial matrix.
• Carnitine is the carrier by forming a fatty acyl-carnitine ester.
![Page 25: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/25.jpg)
Beta-oxidation
• Step 1: Acyl-CoA dhydrogenase and its coenzyme FAD remove hydrogen atoms forming (C=C) and forming FADH2.
• Step 2: The (C=C) is hydrated into (OH-) group.
• Step 3: the (-OH) group is oxidized into a carbonyl group (C=O) and NAD+ is reduced.
• Step 4: the acetyl group is detached to a coenzyme A and the fatty acid is 2 carbons shorter.
![Page 26: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/26.jpg)
How much energy is produced from beta-oxidation of a fatty acid?• Know number of carbons of a fatty acid– Divide by two. This gives you the number of acetyl CoA
produced from this fatty acid that will enter the citric acid cycle
• Each acetyl CoA produces 1 ATP, 3 NADH, and 1 FADH2.– 1 NADH = 2.5 ATP molecules; 1 FADH2 = 1.5 ATP molecules
• Each cycle of beta-oxidation produces 1 NADH and 1 FADH2. This equals 4 ATP molecules.– Number of cycles = number of acetyl CoA – 1
• Subtract 2 ATP molecules needed to activate the fatty acid
![Page 27: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/27.jpg)
Exercises
• How many ATP molecules can lauric acid (a 12-carbon fatty acid)? Lauric acid is equivalent to glucose (similar molecule weight). Compare production of ATP by lauric acid to that of glucose (glucose can produce 30-35 ATP molecules).
• How much ATP does beta-oxidation of palmitic acid produce?
![Page 28: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/28.jpg)
Ketone bodies
• They are produced in the liver when there is excess lipid catabolism
• They are hydrphilic– They can travel though
the bloodstream without the need of a carrier
![Page 29: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/29.jpg)
Ketogenesis (know the steps)
•Location: mitochondria
•Acetone is formed in the bloodstream by the non-enzymatic decomposition of acetoacetate and is excreted by exhalation.
• ketone bodies do not need protein carriers to travel in the bloodstream. Once formed, they become available to all tissues.
Reversal of last step of -oxidation
![Page 30: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/30.jpg)
Use of ketone bodies (important)
• The skeletal muscles of a well fed and healthy person derive a small portion of their daily energy needs from acetoacetate.
• Heart muscles prefer ketone bodies over glucose when fatty acids are in short supply.
• When energy production from glucose is inadequate due to starvation, the production of ketone bodies accelerates.
• During the early stages of starvation, heart and muscle tissues burn larger quantities of acetoacetate, to preserve glucose for use in the brain.
• In prolonged starvation, the brain gets 75% of its energy needs by switching to ketone bodies.
![Page 31: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/31.jpg)
Ketosis
• Overproduction of ketone bodies (diabetes)• Ketosis results in:– Ketonuria (ketone bodies in urea) dehydration– Ketonemia (ketone bodies in blood)– Ketoacidosis (drop in blood pH) labored breathing
![Page 32: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/32.jpg)
Ketoacidosis
• Because two of the ketone bodies are carboxylic acids, continued ketosis (as in untreated diabetes) leads ketoacidosis (acidosis resulting from increased concentrations of ketone bodies in the blood).
• The blood buffers cannot control blood pH, which drops. • An individual experiences dehydration due to increased
urine flow, labored breathing because acidic blood is a poor oxygen carrier, and depression.
• Ultimately, if untreated, the condition leads to coma and death.
![Page 33: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/33.jpg)
Start of lipogenesis(biosynthesis of fatty acids)• Excess of acetyl-CoA from
catabolism of carbohydrates and proteins are diverted into formation of fatty acids that can then be stored.
• Location: cytosol• Production of acetyl-CoA and
malonyl-CoA, which are linked to acyl-carrier protein (ACP) in the enzyme
• Note: need of ATPLink to enzyme
via ACP
Link to enzyme via ACP
![Page 34: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/34.jpg)
Fatty acid synthase
• It is a multienzyme complex that contains all six of the enzymes needed for lipogenesis, with a protein called acyl carrier protein (ACP) anchored in the center of the complex.
• Remember: pyruvate dehydrogenase complex
![Page 35: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/35.jpg)
Lipogenesis
• Condensation, reduction, dehydration, reduction
Note; use of NADPH
![Page 36: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/36.jpg)
Repeat steps
In each step, malonyl-CoA is added to the reaction
![Page 37: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/37.jpg)
Lipogenesis (Biosynthesis of fatty acids)
Oxidation Synthesis
Site of reaction Mitochondria Cytosol
Enzymes Different from each other
Carrier of intermediates Coenzyme A Acyl carrier proteins
Conenzymes FAD, NAD NADPH
Carbon removal and addition
Two carbons removed at a time
Two carbons added at a time
![Page 38: Metabolism of lipids Dr. Mamoun Ahram Biochemistry for Nursing Summer 2015](https://reader035.vdocument.in/reader035/viewer/2022081508/56649ebc5503460f94bc4a63/html5/thumbnails/38.jpg)
Can proteins be used to produce energy?
• Yes, but when?– When the body does not have lipids and
carbohydrates to produce energy