BCM 202 : GENERAL
MEDICAL BIOCHEMISTRY II
CREDIT: 3 UNITS
Dr T.G Atere
COURSE LECTURER
Course Schedule
• WEEK 8 : Structures and classifications of lipids
• WEEK 9: Fate of dietary lipids
• Lipid metabolism in well-feed state,fasting state, diabetes mellitus and
obesity
• Week 10: Ketogenesis, ketolysis and ketosis
• Hormonal influence on fat metabolism
• Disorders of lipid metabolism
Lipids constitute a heterogeneous group of compounds of biochemical
importance.
Lipid is defined as are substances of biological origin that are soluble in
organic solvents such as chloroform and methanol but are only
sparingly soluble, if at all, in water
Function of Lipids
1. Storage form of energy (triglycerides)
2. Structural components of biomembranes (phospholipids and
cholesterol)
3. Metabolic regulators (steroid hormones and prostaglandins)
4. Act as surfactants, detergent and emulsifying agents
(amphipathic lipids)
5. Acts as electric insulators in neurons
6. Provide insulation against changes in external temperature
(subcutaneous fat)
7. Give shape and contour to the body
8. Protect internal organs by providing a cushioning effect
(pads of fat)
9. Help in absorption of fat soluble vitamins (A, D, E and K)
10. Improve taste and palatability of food
Clinical Applications
1. Excessive fat deposits cause obesity.
2. Abnormality in cholesterol and lipoprotein metabolism leads to
atherosclerosis and cardiovascular diseases
3. In diabetes mellitus, the metabolisms of fatty acids and lipoproteins
are deranged, leading to ketosis
Classification of lipids
1. Simple lipids: They are esters of fatty acids with
glycerol or other alcohols
2. Compound lipids: They are fatty acids esterified
with alchohol; but in addition they contain other
groups. They are sub classified as (a) Phospholipids,
containing phosphoric acid
(b)Non-phosphorylated lipids
3. Derived lipids: They are compound which are
derived from lipids or precursors of lipids e.g. Fatty
acids, steroids
4. 4. Lipid complexed to other compounds
I. Simple Lipids
a. Triacyl glycerol or Triglycerides or neutral fat b. Waxes
II. Compound Lipids
A. Phospholipids, containing phosphoric acid.
1. Nitrogen containing glycerolphosphatides:
i. Lecithin (phosphatidyl choline) ii.Cephalin (phosphatidyl ethanolamine)
iii. Phosphatidyl serine
2. Non-nitrogen glycerophosphatides
i. Phosphatidyl inositol ii. Phosphatidyl glycerol
iii. Diphosphatidyl glycerol (cardiolipin)
3. Plasmologens, having long chain alcohol
i. Cholineplasmogen ii. Ethanolamine plasmalogen
4. Phospho sphingosides, with sphingosine Sphingomyelin
B. Non-phosphorylated lipid
1. Glycosphingolipids (carbohydrate)
i. Cerebrosides (ceramide monohexosides)
ii. Globosides (ceramide oligosaccharides)
iii. Ceramide + oligosaccharides + N- acetyl neuraminic acid
2. Sulpholipids or sulfatide
i. Sulphated cerebrosides ii. Sulphated globosides iii. Sulphated gangliosides
III. Derived Lipids
Structure of fats
• Fats are esters of the trivalent alcohol glycerol with
three fatty acids. When a single fatty acid is esterified
with glycerol, the product is referred to
residue=acylresidue). as a monoacylglycerol (fatty
acid
• Esterification with additional fatty acids leads to
diacylglycerol and ultimately to triacylglycerol, the
actual fat (formerly termed “triglyceride”). As
triacylglycerols are uncharged, they are also referred
to as neutral fats
Fats contd
• Triacylglycerols (fats or triglycerides) consist of three fatty acid chains
esterified to a glycerol backbone.
• Simple triacylglycerols have three identical fatty acids,
• mixed triacylglycerols have two or three different fatty acids.
Structure of (a) a simple triacylglycerol (1,2,3-tripalmitoyl-
glycerol) and (b) a mixed
triacylglycerol (1-palmitoyl-2,3-dioleoyl-glycerol).
• Triacylglycerols are the major energy store and the
major dietary lipid in humans, triacylglycerols
• constitute the major fuel store and the major dietary
lipid in humans. They are insoluble in water and are
stored in specialized adipose (fat) cells. These cells
are specialized for the synthesis and storage of
triacylglycerols and for their mobilization into fuel
molecules.
• Triacylglycerols are a highly concentrated energy
store. The energy yield from the complete oxidation
of fatty acids is about 39 kJ g–1, compared with an
energy yield of 13 kJ g–1of carbohydrate or protein.
The hydrophobic properties of fats
• Triacylglycerols are transported round the body in
large lipid–protein particles called lipoproteins
Lipid Metabolism in the Fed State
• 1) Dietary fat (triglyceride) is hydrolyzed to free fatty acids and glycerol (actually monoacylglycerol) in
the intestine by pancreatic lipase (PL).
• 2) Short chain fatty acids can enter the circulation directly, but most fatty acids are reesterified with
glycerol in the epithelial cells of the intestine. The resulting triglycerides enter the circulation as
lipoprotein particles called chylomicrons through the lymphatic system.
• 3) The triglycerides in chylomicrons can be cleared by lipoprotein lipase (L) at the endothelial surface
of capillaries. The resulting fatty acids can be: a) stored as fat in adipose tissue (Note: Triglycerides
(fat) can also be made from excess glucose in the fed state); b) used for energy in any tissue with
mitochondria and an ample supply of O 2 . (Note: Most tissues will be relying on glucose as their
primary energy source in the fed state. The exception would be exercising muscle); and c) reesterified
to triglycerides in the liver and exported as lipoproteins called VLDL. (Note: Triglycerides and VLDL can
also be synthesized from excess glucose and amino acids in the liver during the fed state)
• 4) VLDL has essentially the same fate as the chylomicrons
• 5) Insulin simulates lipoprotein lipase. It also stimulates fatty acid and triglyceride synthesis in liver
and adipose tissue and inhibits hormone sensitive lipase in the adipose tissue.
Lipid Metabolism During Fasting & Exercise
• 1) Glycogen breakdown provides glucose and protein breakdown provides alanine, which is converted to
glucose in the liver. The blood glucose is used by the brain and red blood cells. Most other tissues,
including resting muscle, are relying primarily on fatty acids as an energy source. Exercising muscle will use
both fatty acids and glucose for energy. The relative contribution these energy sources depends on the
intensity of the exercise.
• 2) Hormone-sensitive lipase is activated by glucagon (fasting) or epinephrine (exercise). Therefore, fat in
adipose tissue is hydrolyzed to give glycerol and fatty acids during both fasting and exercise.
• 3) The fatty acids can be used directly as an energy source by most tissues with mitochondria, excluding
the brain
• 4) The glycerol can be converted to glucose in the liver. This is a minor source of glucose.
• 5) Glucagon & epinephrine stimulate hormone-sensitive lipase and inhibit lipoprotein lipase, fatty acid
synthesis and triglyceride synthesis
• 6) During prolonged starvation, the fatty acids can also be converted to ketone bodies in the liver. These
ketone bodies can be used as an energy source by all tissues except those lacking mitochondria (eg. red
blood cells). Brain adapts slowly to the use of ketone bodies during prolonged starvation.
Ketone bodies
• When the level of acetyl CoA from β-oxidation increases in excess of that
required for entry into the citric acid cycle, the acetyl CoA is converted into
acetoacetate and D-3-hydroxybutyrate by a process known as ketogenesis. D-3-
hydroxybutyrate, acetoacetate and its nonenzymic breakdown product acetone
are referred to collectively as ketone bodies.
Two molecules of acetyl CoA initially condense to form acetoacetyl CoA in a reaction which is essentially
the reverse of the thiolysis step in β-oxidation. The acetoacetyl CoA reacts with another molecule of
acetyl CoA to form 3-hydroxy-3-methylglutaryl CoA (HMG CoA).
Further Reading
i. Lecture notes
ii. Lehninger Principles of Biochemistry. 4th ed: Chapters 10
iii. Garrett and Grisham Biochemistry 2nd ed :
iv. Voet and Voet:
v. Elsevier Biochemistry:
vi. Colour Atlas of Biochemistry 2nd ed pg 38-48
vii. Stryer 6th ed:
