Lipids Metabolism study guide biochemistry

TRIACYLGLYCEROL
TRIACYLGLYCEROL REVIEW
 TAG is the most prevalent acylglycerol. It is the major lipid taken from the diet.
 Highly reduced and anhydrous
 Nonpolar, insoluble to water, neutral

 Structure:
 Three fatty acids esterified to a glycerol molecule
 Fatty acid on carbon 1 – typically saturated
 Fatty acid on carbon 2 - typically unsaturated
 Fatty acid on carbon 3 – can be either
 Fatty acids are esterified through their carboxyl groups, resulting in a loss of
negative charge and formation of “neutral fat.” (Harvey and Ferrier, 2011)

 Functions:
 Major storage form (adipose tissue)
 Transport form (liver) of fatty acids
 Source of energy when carbohydrates are not available
 Liver can synthesize fatty acids but store little of them because majority is
transported to the tissues
TRIACYLGLYCEROL SYNTHESIS
MONOACYLGLYCEROL PATHWAY GLYCEROL-3-PHOSPHATE PATHWAY




Occurs in the intestine
 2-monoacylglycerol as a product of TAG digestion in the
intestine
Used in reformation of TAGs after their previous hydrolysis from
chylomicrons Two organ sites
 Liver – for transport via LDL
Monoacylglycerol acyltranferase (MGAT) o Primary site of TAG synthesis
 Unique to the monoacylglycerol pathway  Adipose tissue – for storage
 DGAT present in glycerol-3-phosphate pathway
Catalyzed by enzymes in the endoplasmic reticulum and some in
No phosphatidic acid intermediate versus glycerol-3-phosphate mitochondria
pathway

*pathway not emphasized in Harper’s but we added it below anyway
*pathway not emphasized in Harper’s but we added it below because bida-bida tayong lahat
anyway because bida-bida tayong lahat
REGULATION OF SYNTHESIS
 Synthesis of TAG with some phospholipids (phosphatidylcholine and phosphatidylethanolamine) driven by the availability of free fatty
acids
 Free fatty acids not oxidized are converted to phospholipids, and if this requirement is satisfied they are used for TAG synthesis


Condition with excessive accumulation of fat in the body, associated with
increase in number and size of adipocytes as a result of packing of TAG
OBESITY
CLINICAL
Occurs when caloric intake >>> amount needed for body function and
SIGNIFICANCE
work needed to be done

Prolonged elevated level of of triacylglycerol
HYPERTRIACYLGEREDEMIA




TRIACYLGLYCEROL CATABOLISM
A collaborative effort of 1A and 1D
Lipid Metabolism II | 1

,  Initiated by hormone sensitive lipase in adipose which is activated by
phosphorylation by protein kinase A (PKA) via cAMP
 Hormone sensitive lipase hydrolyzes and removes the first fatty acid in
carbon 1 or 3
 Additional lipases specific for monoacylglycerol or diacylglycerol removes other
fatty acids
 Released fatty acids bind to albumin and transported to tissues for use
 Glycerol returns to liver, where it is converted to dihydroxyacetone to enter
glycolysis or gluconeogenesis

Name Location Function Special Properties
Hormone Adipocytes Fat mobilization Activated by
sensitive phosphoryltion thru
lipase action of cAMP
dependent protein kinase
Pancreatic Pancreatic Digestion of Hydrolyzes TAGs in
lipase juice dietary mixed micelles; activity
triacylglycerol enhanced by co lipase
Acid lipase Lysosome Intracellular pH optimum of about 5.0
catabolism of
lipoproteins
Lipoprotein Capillaries Utilization of TAG Released into plasma by
lipase in lipoproteins heparin , inhibited by
protamine
Hepatic Liver Lipoprotein Released into plasma by
lipase catabolism heparin , inhibited by
protamine



FATTY ACID MOBILIZATION FROM ADIPOSE  Factors that affect mobilization:
TISSUES  Fasting (unfed condition)
 causes release of glucagon (↓ insulin)
 ↑ cAMP → ↑ Protein Kinase A → ↑ activation of hormone-sensitive
lipase
 Sympathetic nervous system dishcharge (norepinephrine)
 Hormones: epinephrine, adenocorticotropic hormone (ACTH), growth
hormone, glucagon
 Activate hormone-sensitive lipase → ↑ FA mobilization
 Caffeine and theophylline (anti-asthma drug)
 Enhance FA mobilization by inhibiting phosphodiesterase which
inactivates cAMP
 ↑ cAMP → ↑ Protein Kinase A → ↑ activation of hormone-sensitive
lipase




FATTY ACID ACCUMULATION IN ADIPOSE TISSUE  ↑ glucose (FED state) and insulin
 ↑ accumulation of TAG in adipose tissues
 Due to release of lipoprotein lipase from capillaries to adipocytes
 Lipoprotein lipase releases fatty acids in lipoproteins (VLDL or
chylomicron)
 Released FA used to synthesize TAGs and store them
 Released glycerol used in carbohydrate metabolism




(this part is not emphasized in the lecture and in Harper’s)
MONOACYLGLYCEROL PATHWAY
A collaborative effort of 1A and 1D
Lipid Metabolism II | 2

, 1 Monoacylglycerol acyltransferase
(MGAT)

Addition of an acyl group to:
- Carbon 1 to form 1,2-DAG, or
- Carbon 3 to form 2,3-DAG




2 Diacylglycerol acyltransferase (DGAT)

Addition of an acyl group to:
- Last free carbon of glycerol




(this part is not emphasized in the lecture and in Harper’s)
GLYCEROL-3-PHOSPHATE PATHWAY
1. Glycerol-3-phosphate acyltransferase (GPAT)
Co-enzyme: Fatty-acid coenzyme A ester (FA-CoA)

Glycerol-3-phosphate:
Initial acceptor of fatty acids during TAG synthesis



2. Acylglycerol phosphate acyltransferase (AGPAT)
Co-enzyme: Fatty-acid coenzyme A ester (FA-CoA)
Reaction:
Addition of fatty acids / acylation of two free hydroxyl groups of glycerol-3-
phosphate:
- 1st OH – lysophosphatidic acid
- 2nd OH – Phosphatidic acid

Phosphatidic acid
- aka diacylglycerol-3-phosphate
- important intermediate for the synthesis of TAG and phospholipids
- Considered the simplest phosphoglyceride
- Found only in trace amounts in cells




3. Phosphatidic acid phosphorylase (AGPAT)
Reaction:
Removal of the phosphate group from phosphatidic acid to produce DAG




A collaborative effort of 1A and 1D
Lipid Metabolism II | 3