4. Compartmentalization of Metabolic
Pathways
• Eukaryotes use organelles to compartmentalize metabolic pathways allowing
different metabolic pathways to occur in specific locations.
• Mitochondrion - Citric acid cycle, oxidative phosphorylation, amino acid
catabolism.
• Cytosol – Glycolysis, pentose phosphate pathway, fatty acid biosynthesis,
gluconeogenesis.
• Nucleus – DNA replication, RNA transcription, RNA processing.
• Lysosomes – Enzymatic digestion of cellular components.
• Golgi Apparatus – Post translational modification of membrane and
secretory proteins, formation of plasma membranes and secretory vesicles.
• Rough Endoplasmic Reticulum – Synthesis of membrane-bound and
secretory proteins.
• Smooth Endoplasmic Reticulum – Lipid and steroid biosynthesis.
• Peroxisomes - Oxidative reactions involving amino acid oxidases and
catalase, glyoxylate cycle reactions in plants.
• In multicellular organisms compartmentation is carried a step further to the
level of tissues and organs. For example, the liver is largely responsible for
the synthesis of glucose from noncarbohydrate precursors to maintain a
constant level of glucose in the blood stream. Adipose tissue is specialized
for the storageof triacylglycerols.
8. 8
• The dietary carbohydrates and amino acids, when consumed in excess,
can be converted to fatty acids and stored as triacylglycerols.
• De novo (new) synthesis of fatty acids occurs predominantly in liver,
kidney, adipose tissue and lactating mammary glands.
• The enzyme machinery for fatty acid production is located in the
cytosomal fraction of the cell.
• Acetyl CoA is the source of carbon atoms while NADPH provides the
reducing equivalents and ATP supplies energy for fatty acid formation.
Introduction
9. 9
• Fatty acids are main constituents of oils and fats.
• They posses simple a simple structure consisting of long hydrocarbon
side chain and carboxylic acids.
• Fatty acids mainly occur in the esterified, some are free (unesterified)
fatty acids.
• They are found in both plants and animals.
• Fatty acids of animal origin are much simpler in structure in contrast to
those of plant.
What are fatty acids?
10. 10
• Most of the fatty acids that occur in natural lipids are of even carbons
(usually 14C-20C).
• This is due to the fact that biosynthesis of fatty acids mainly occurs
with the sequential addition of 2 carbon units.
• Palmitic acid (l6C) and stearic acid (l8C) are the most common.
Saturated and unsaturated fatty acids
12. 12
• Saturated fatty acids (solid in nature) do not contain double bonds,
while unsaturated fatty acids (liquid in nature) contain one or more double
bonds.
• Both saturated and unsaturated fatty acids almost equally occur in the
natural lipids.
• Fatty acids with one double bond are monounsaturated and those with
2 or more double bonds are collectively known as polyunsaturated fatty
acids (PUFA).
14. 14
I. Production of acetyl CoA and NADPH
ll. Conversion of acetyl CoA to malonyl CoA
lll. Reactions of fatty acid synthesis complex
Fatty acid synthesis
15. 15
• Acetyl CoA and NADPH are the prerequisites for fatty acid synthesis.
• Acetyl CoA is produced in the mitochondria by the oxidation of pyruvate and fatty acids, degradation of carbon
skeleton of certain amino acids, and from ketone bodies.
• Mitochondria, however, are not permeable to acetyl CoA.
• An alternate or a bypass arrangement is made for the transfer of acetyl CoA to cytosol.
• Acetyl CoA condenses with oxaloacetate in mitochondria to form citrate.
• Citrate is freely transported to cytosol where it is cleaved by citrate lyase to liberate acetyl CoA and oxaloacetate.
Production of acetyl CoA and NADPH
17. 17
Acetyl CoA is carboxylated to malonyl CoA by the enzyme acetyl CoA carboxylase. This is an ATP-dependent
reaction and requires biotin for CO2 fixation.
Conversion of acetyl CoA to malonyl CoA
26. Chemical Nature of Fatty Acids and Acylglycerols
Fatty Acids Are Alkyl Chains Terminating in a Carboxyl Group
Fatty acids consist of an alkyl chain with a terminal carboxyl group, the
basic formula of completely saturated species being CH3–(CH2) n–
COOH.
The important fatty acids for humans have relatively simple structures,
although in some organisms they may be quite complex, containing cy
clopropane rings or extensive branching.
Unsaturation occurs commonly in human fatty acids, with up to six dou
ble bonds per chain, these being almost always of the cis configuration.
If there is more than one double bond per molecule, they are always se
parated by a methylene (–CH2) group.
27.
28.
29.
30.
31.
32. Cholesterol biosynthetic pathway. The
regulated rate-controlling step in cholesterol
biosynthesis is the conversion of -hydroxy--
methylglutaryl CoA (HMG-CoA) into mevalonic
acid by HMG-CoA reductase, an ER-membrane
protein. Mevalonate is then converted into
isopentenyl pyrophosphate (IPP), which has
the basic five-carbon isoprenoid structure. IPP
can be converted into cholesterol and into
many other lipids, often through the
polyisoprenoid intermediates shown here.
Some of the numerous compounds derived
from isoprenoid intermediates and cholesterol
itself are indicated.
