1. Dr. Diala Abu-Hassan, DDS, PhD
Lipid Metabolism
Dr. Diala Abu-Hassan, DDS, PhD
Nursing
All images were taken from McMurry et al except where noted
Dr. Diala Abu-Hassan00

2. Digestion of triacylglycerols (TAGs)
TAGs are not water-soluble but they must enter an aqueous environment
TAGs are packaged in various kinds of lipoproteins
Energy can drive chemical reactions that are not favorable at body temperatures.
Dr. Diala Abu-Hassan
Dr. Diala Abu-Hassan

3. Lipoproteins
In the duodenum, pancreatic lipases and bile acids are released to emulsify the TAGs by forming micelles
Dr. Diala Abu-Hassan

4. Bile salts
Bile acids (derived from cholesterol) and cholesterol, which are steroids, and phospholipids are released to emulsify the TAGs by forming micelles
Dr. Diala Abu-Hassan

5. TAGs Digestion
Dr. Diala Abu-Hassan

6. Pathways of lipids through the villi
Lipoproteins (chylomicrons ) – lacteal- thoracic duct- blood
Dr. Diala Abu-Hassan

7. Sources of lipids from the digestive tract as food is broken down
(2) from adipose tissue, where excess lipids have been stored
(3) from the liver, where lipids are synthesized.
Dr. Diala Abu-Hassan

8. Lipid transport
10 FA by 1 albumin
Dr. Diala Abu-Hassan

9. Types of lipoproteins
1. Very-low-density lipoproteins (VLDLs) carry TAGs from the liver (where they are synthesized) to peripheral tissues for storage or energy generation.
2. Intermediate-density lipoproteins (IDLs) carry remnants of the VLDLs from peripheral tissues back to the liver for use in synthesis.
3. Low-density lipoproteins (LDLs) transport cholesterol from the liver to peripheral tissues, where it is used in cell membranes, for steroid synthesis, or for formation of arterial plaque
4. High-density lipoproteins (HDLs) transport cholesterol from dead or dying cells back to the liver, where it is converted to bile acids.
Dr. Diala Abu-Hassan

10. Metabolism of triacylglycerols
Dr. Diala Abu-Hassan

11. Dietary Triacylglycerols
TAG hydrolysis occurs when chylomicrons in the bloodstream
encounter lipoprotein lipase anchored in capillary walls.
Fatty acids (FAs) are then:
(1) When energy is in good supply, they are converted
back to TAGs for storage in adipose tissue
(2) When cells need energy, the FA carbon atoms are activated by conversion to fatty acyl-SCoA and then oxidized as acetyl-SCoA
Acetyl-SCoA is the starting material for the biosynthesis of fatty acids (lipogenesis) in the liver and the synthesis of cholesterol
Acetyl-SCoA enters the ketogenesis pathway for production of ketone bodies
Dr. Diala Abu-Hassan

12. Triacylglycerols from Adipocytes
When stored TAGs are needed as an energy source, lipases within fat cells are activated by hormones (insulin and glucagon)
The stored TAGs are hydrolyzed to FAs and glycerol- blood (in association with albumins to cells (primarily muscle and liver cells))- acetyl-SCoA - energy generation.
Dr. Diala Abu-Hassan

13. Glycerol from Triacylglycerols
Glycerol- blood to kidney and liver - converted glyceraldehyde
3-phosphate and dihydroxyacetone phosphate (DHAP)
DHAP, a reactant in the synthesis of triacylglycerols, enters the glycolysis pathway
Dr. Diala Abu-Hassan

14. Storage and Mobilization of Triacylglycerols
TAGs are the primary energy storage form.
TAGs are stored in the adipose tissue
After a meal, insulin activates the synthesis of TAGs for storage.
After a meal, blood glucose levels increase rapidly, insulin
levels rise, and glucagon levels drop. Glucose enters cells, and the rate of glycolysis increases.
Dr. Diala Abu-Hassan
Dr. Diala Abu-Hassan

15. TAG Mobilization
When digestion of a meal is finished, blood glucose levels return to normal, insulin levels drop and glucagon levels rise.
This activates triacylglycerol lipase to start the hydrolysis of stored TAGs.
When glycerol 3-phosphate is in short supply (glycolysis is not producing sufficient energy) the FAs and glycerol produced by TAG hydrolysis are released to the bloodstream for transport to energy-generating cells.
Otherwise, the fatty acids and glycerol are cycled back into new TAGs for storage.
Dr. Diala Abu-Hassan

16. Oxidation of Fatty Acids
A fatty acid enters the cytosol of a cell that needs energy then,
1. Activation
2. Transport to mitochondria
Carnitine, an amino-oxy acid, undergoes a transesterification reaction with the fatty acyl- SCoA, resulting in a fatty acyl carnitine ester that moves across the membrane into the mitochondria by facilitated diffusion.
3. β-Oxidation Pathway
Dr. Diala Abu-Hassan

17. β-Oxidation of Fatty Acids
3. β-Oxidation Pathway: fatty acyl-SCoA is oxidized to acetyl-SCoA and the reduced coenzymes to be used in ATP generation.
Spiral pathway (4 steps repeated or each 2 carbon fragment)
Dr. Diala Abu-Hassan

18. Energy from Fatty Acid Oxidation
Lauric acid
Carbohydrates yield 4 Cal/g, whereas fats and oils yield 9 Cal/g
Dr. Diala Abu-Hassan

19. Ketone Bodies Ketone body formation in liver mitochondria
Acetoacetate is somewhat unstable
Ketone bodies are water soluble, thus, they do not need protein carriers to travel in the bloodstream
Dr. Diala Abu-Hassan

20. Ketogenesis
It is the synthesis of the three ketone bodies from acetyl-SCoA
Ketogenesis occurs in four enzyme-catalyzed steps plus the spontaneous decomposition of acetoacetate.
The enzyme for the
pathway, also found in mitochondria, has the same name but is specific for the L
form of 3-hydroxy-3-methylglutaryl-SCoA. The pathways are separated by the
specificity of the enzymes for their respective substrates.
(HMG-CoA)
Dr. Diala Abu-Hassan
Dr. Diala Abu-Hassan

21. 3-hydroxybutyrate dehydrogenase
Ketogenesis
3-hydroxybutyrate dehydrogenase
The enzyme for the
pathway, also found in mitochondria, has the same name but is specific for the L
form of 3-hydroxy-3-methylglutaryl-SCoA. The pathways are separated by the
specificity of the enzymes for their respective substrates.
Dr. Diala Abu-Hassan
Dr. Diala Abu-Hassan

22. Ketogenesis
In normal person, skeletal muscles derive a small portion of their daily energy needs from acetoacetate, and heart muscles use it in preference to glucose when fatty acids are in short supply.
During early stages of starvation, heart and muscle tissues burn more acetoacetate and save glucose for brain tissue
In diabetic patients, more ketone bodies are produced than they are utilized (ketosis)
Ketosis is indicated by the odor of acetone (a highly volatile ketone) on the patient s breath and the presence of ketone bodies in the urine (ketonuria) and the blood (ketonemia).
The enzyme for the
pathway, also found in mitochondria, has the same name but is specific for the L
form of 3-hydroxy-3-methylglutaryl-SCoA. The pathways are separated by the
specificity of the enzymes for their respective substrates.
Dr. Diala Abu-Hassan
Dr. Diala Abu-Hassan

23. Biosynthesis of Fatty Acids (lipognesis)
Fatty acids are synthesized from acetyl-SCoA
Acetyl-SCoA is an end product of carbohydrate and amino acid catabolism
Using acetyl-SCoA to make fatty acids allows the body to use the excess energy of carbohydrates and amino acids into storage as TAGs
The enzyme for the
pathway, also found in mitochondria, has the same name but is specific for the L
form of 3-hydroxy-3-methylglutaryl-SCoA. The pathways are separated by the
specificity of the enzymes for their respective substrates.
Dr. Diala Abu-Hassan
Dr. Diala Abu-Hassan

24. Fatty acid synthesis (lipogenesis)
FA synthase complex
The enzyme for the
pathway, also found in mitochondria, has the same name but is specific for the L
form of 3-hydroxy-3-methylglutaryl-SCoA. The pathways are separated by the
specificity of the enzymes for their respective substrates.
(Fatty acid synthase 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.)
Dr. Diala Abu-Hassan
Dr. Diala Abu-Hassan

25. Fatty acid synthesis (lipogenesis)
Palmitic acid production (16 carbons)
Step 1: Condensation
Steps 2-4
Reduction
Dehydration
7 times
The enzyme for the
pathway, also found in mitochondria, has the same name but is specific for the L
form of 3-hydroxy-3-methylglutaryl-SCoA. The pathways are separated by the
specificity of the enzymes for their respective substrates.
Dr. Diala Abu-Hassan
Dr. Diala Abu-Hassan