DE NOVO SYNTHESIS OF

FATTY ACIDS & EICOSANOIDS

Dr. Ralph Cylon M. Jacinto
Objectives
◻ Review the different classifications of fatty acids.
◻ Describe the reactions involved in fatty acid
biosynthesis.
◻ Define nutritionally essential fatty acids and
eicosanoids.
Fatty Acids
◻ Aliphatic carboxylic acids
◻ Classifications of fatty acids:
1. Saturated
2. Unsaturated
A. Monounsaturated
B. Polyunsaturated
C. Eicosanoids
De Novo Synthesis of Fatty Acids
◻ Location: Cytosol
◻ Present in many tissues: Liver, kidneys, brain, lungs,
mammary glands and adipose tissues
◻ Cofactors: NADPH, ATP, Mn2+, Biotin, HCO3-
◻ Immediate substrate: Acetyl-CoA
◻ Rate-limiting enzyme: Acetyl-CoA carboxylase
◻ End product: Long chain fatty acids (usually palmitic
acid)
Acetyl-CoA Carboxylase
Fatty Acid Synthase Complex
◻ Multifunction enzyme
complex
Adv:
Compartmentalization
within the cytoplasm
without the need for
barriers
Acyl(Acetyl)-Malo
nyl Enzyme
3-Hydroxyacyl 3-Ketoacyl Acyl(Acetyl)-Malo
enzyme (Acetoacetyl) Enzyme nyl Enzyme
2,3-Unsaturated Acyl-Malonyl
Acyl enzyme
acyl enzyme Enzyme
Reactions involved:
1. Condesation of malonyl group with acetyl (acyl).
2. Reduction of keto-acyl to hydroxy-acyl.
3. Formation of double bond through dehydration.
4. Reduction of double bond to saturated fatty acyl.
Sources of Reductant
◻ NADPH from:
Pentose Phosphate Pathway (major) – 2
NADPH/Glucose
Malate to pyruvate via malic enzyme
(NADP-dependent malate dehydrogenase)
Fates of Fatty Acids
1. Esterification into TAG
2. Esterification into cholesteryl esters
3. Chain elongation
4. Desaturation 🡪 Mono- and polyunsaturated FA

◻ In mammary glands, separate thioesterase for C8,

C10, C12 🡪 milk lipids
Esterification of Fatty Acids
◻ Either to form TAG or cholesteryl esters
Chain Elongation
◻ “Microsomal lipogenesis”
◻ Location: Endoplasmic reticulum
◻ Produces long chain saturated and unsaturated
fatty acyl-CoA (C10 upwards)
◻ 2-Carbon donor: Malonyl-CoA
◻ Reductant: NADPH
◻ Enzyme: Fatty acid elongase enzyme system
Elongation of Stearyl-CoA
◻ Increases rapidly during myelination
To provide C22 and C24 fatty acids 🡪 Sphingolipids
Regulation of Lipogenesis
Hormonal Regulation of Lipogenesis
Desaturation of Fatty Acids
Monounsaturated Fatty Acids
Essential Fatty Acids
◻ Animals including humans 🡪 cannot introduce double
bonds beyond Δ9
Polyunsaturated Fatty Acids
◻ Arachidonic acid 🡪 Derived from linoleic acid (ω6,
18:2, Δ9,12)
Deficiencies in Essential Fatty Acids
◻ EFA: Precursor of eicosanoids
Structural lipids of cells 🡪 Position 2 of phospholipids
Maintains structural integrity of mitochondria
Arachidonic acid: 5-15% of FA in phospholipids
DHA: High conc. in retina, cerebrum, testis

◻ EFA deficiency: ω9 FA replaces EFA

Tissues cannot function properly
Eicosanoids
◻ From C20 Polyunsaturated fatty acids
◻ Include: Prostaglandins, Thromboxanes, Leukotrienes,
Lipoxins
◻ Act as local hormones 🡪 G protein-coupled
receptors
Prostanoid Synthesis
◻ Involves Cyclooxygenase (COX/Prostaglandin H
synthase)
Activities: Cyclooxygenase and peroxidase
Isoenzymes: COX-1 (constitutive) and COX-2 (inducible)
Lipoxygenase Pathway
◻ Found in leukocytes, platelets and macrophages
◻ Produces leukotrienes and lipoxins
5-Lipoxygenase 🡪 Leukotrienes
Clinical Correlation
◻ Trans Fatty Acids 🡪 Replace EFA in membranes
Structurally similar to saturated FA
◻ Physiologic effects of prostaglandins, thromboxanes,
leukotrienes and lipoxins
Trans Fatty Acids
Thank you!