3. Classification of Fatty Acids
a. Depending on total no. of carbon atoms
a. Even chain
b. Odd chain
b. Depending on the length of hydrocarbon chain
a. Short chain 2-6C
b. Medium chain 8-14C
c. Long chain 16-24C
d. Very long chain >24C
c. Depending on nature of hydrocarbon chain
a. Saturated
b. Unsaturated
5. FATTY ACID OXIDATION
• Principal pathway for catabolism of fatty acids
• To meet the energy requirement of an organism
• Major source in cardiac and skeletal muscles.
• ALPHA OXIDATION
• BETA OXIDATION
• OMEGA OXIDATION
6. BETA OXIDATION
• Oxidation and splitting of 2C units occurs at beta
carbon atom
• Oxidation occurs by sequential cleavage of two
carbon units
• Occurs in mitochondrial matrix of liver, muscle,
kidney ,adipose tissue etc.
• Not occur in brain and RBCs .
9. ACTIVATION OF FATTYACIDS
• Cytoplasm
• 2 high energy bonds are utilised
• Enzyme-thiokinase/fatty acyl CoA Synthetase
•Outer Mitochondrial Membrane
• Three different enzymes-
• Short chain
• Medium chain
• Long chain
10. ROLE OF CARNITINE
• CARNITINE- carrier that transports
long chain fatty acyl CoA into mitochondria
• Carnitine shuttle
○ Carnitine acyl transferase I
○ Translocase
○ Carnitine acyl transferase II
• Short and medium chain fatty acids donot require
carnitine,so they are easily oxidised
11. CARNITINE
• Transporter molecule of long chain Fatty Acyl CoA from cytoplasm
to mitochondria
• Synthesized from aminoacids-lysine & methionine in liver and
kidney
• Beta hydroxy gamma trimethyl ammonium butyrate
18. Energetics of β oxidation of 16C palmitic acid
Each cycle prooduces 1 FADH2+1 NADH+1 ACETYL Co A
1.5 + 2.5 + 10 ATP
8 ACETYL Co A X 10 = 80 ATP
7 FADH2 X 1.5 = 10.5 ATP
7 NADH X 2.5 = 17.5 ATP
-------
TOTAL 108 ATP
FA activation utilize -2ATP
---------
Net yield from 16 C- 106 ATP
19.
20. Regulation of beta oxidation of fatty acid
1.Availability free fattyacid(FFA)
2. Level of FFA in turn is controlled by glucogon: insulin ratio
glucogon increase FFA , insulin decrease FFA level
3. CAT-1 regulate entry FA into mitochondria- RATE LIMITING
STEP
Malonyl Co A allosterically inhibit CAT-1 activity.(
During FA synthesis beta oxidation is inhibited).
21. Defects Of Beta Oxidation
⮚Deficiency of enzymes of beta oxidation
❖Medium chain Acyl CoA Dehydrogenase deficiency-
• most common inborn error of beta oxidation
• Non ketotic hypoglycemia initiated by fasting
• 10% Sudden Infant Death Syndrome(SIDS)
• Fat accumulation in liver
⮚Carnitine deficiency
⮚CAT/translocase deficiency
22. Carnitine deficiency
• Long chain fatty acids cannot be transported into
mitochondria
• Commonly affects liver and muscles
• Hypoketotic hypoglycemia(during extended fasting)
• Muscle weakness,muscle cramps on exertion(muscle
energy must be derived from glucose which is insufficient for
continued contraction)
• Hepatomegaly
29. Inborn errors of propionate metabolism
Propionic acidemia
• Propionyl CoA Carboxylase deficiency
• Ketoacidosis,developmental abnormalities
Methyl malonic aciduria
• Inherited defect in mutase enzyme/inherited defect in B12
• Methyl malonic acid accumulates in brain
• Life threatening acidosis,CNS damage,growth retardation
• Restrict intake of odd chain fatty acids
• Methyl malonate will affect metabolism of brain leads to MR
30.
31.
32. • Site of α oxidation - ER
• Oxidation occur in alpha Carbon
• It is for the oxidation of long chain branched FA which has
CH3 gp at β carbon which blocks beta oxidation.
• Eg:phytanic acid
α- OXIDATION
33. • Activation of FA is not all required
• Does not generate ATP
• Alpha oxidation is important in brain tissue
• In this process the α carbon atom is first
hydroxylated,oxidized to ketoacid ,later
decarboxylated yielding CO2 and fatty acid with
one carbon less
34.
35. Refsum’s disease
• Lack of alpha hydroxylase/phytanic acid oxidase
• Alpha oxidation doesnot occur,Phytanic acid accumulates in body
lipids
• Branched chain fatty acids will increase the fluidity of neuronal
membranes, affects nerve conduction
• Neurological symptoms-Polyneuropathy,Retinitis pigmentosa,
Cerebellar ataxia,Nerve deafness
• Symptoms regress with restriction of phytanic acid intake(avoid milk)
36.
37. OMEGA OXIDATION
• Minor pathway in microsomes
• Oxidation of medium chain fatty acids,Becomes important when
beta oxidation is defective
• Oxidation of omega carbon/carbon most remote from carboxyl
group to produce dicarboxylic acids
• Methyl group at omega carbon is converted to CH2OH, subsequently
oxidized to COOH group to produce dicarboxylic acids
• Hydroxylase enzyme- NADPH,O2,cytochrome P450
• Dicarboxylic aciduria-defective oxidation
38.
39.
40. PEROXISOMAL OXIDATION
• Modified Beta oxidation of VLCFA(>20 C)
• Shorten very long fatty acid, boosting beta oxidation
• Electrons from FADH2 are directly donated to oxygen to
form H2O2
• Doesnot produce energy, energy is dissipated as heat
41.
42. • Adrenoleucodystrophy
• Defective oxidation of VLCFA
• Myelin sheaths are destroyed
• Zellewegers syndrome
• Impaired oxidation of VLCFA due to absence of
peroxisomes
• Abnormal accumulation of VLCFA in brain,liver,kidney-
cerebrohepatorenal syndrome
43.
44.
45.
46. Organic acidurias
• Disorders of metabolism of fatty acids, branched chain and
aromatic aminoacids,citric acid cycles
• Medium Chain Acyl CoA Dehydrogenase deficiency-most
common(1 in 2500 births)
• Second most common inborn error of metabolism
• Characterised by accumulation of organic acids in body
tissues, excreted in urine
48. • Patient presents with acidosis,vomiting,convulsions,coma
• Children die in infancy
• Severe mental and physical retardation
• Diagnosis-demonstration of organic acids in urine by
chromatography
• Treatment -Dietary restriction, cofactor therapy, substrate
removal
