This document discusses fatty acid metabolism, including the classification, oxidation, and defects of fatty acid breakdown. It covers the following key points: 1. Fatty acids are classified based on carbon chain length and saturation. Beta-oxidation breaks down fatty acids in mitochondria in 2-carbon units, generating acetyl-CoA. 2. Defects in beta-oxidation enzymes or carnitine transport can cause organic acidurias, presenting as hypoglycemia, liver damage, or sudden infant death. 3. Alpha and omega oxidation are minor pathways that break down branched or very long chain fatty acids in the endoplasmic reticulum or peroxisomes. Defects can cause

1. Dr.NISHA ABRAHAM

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

4. Numbering of carbon atoms

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 .

7. PREPARATORY STEPS
➔ACTIVATION OF FATTYACIDS
➔ROLE OF CARNITINE
BETA OXIDATION PROPER

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

17. Beta oxidation of palmitic acid

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

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

24. Beta oxidation of palmitic acid

26. Propionyl CoA is gluconeogenic

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

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

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)

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

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

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

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

47. • MCADH deficiency
• Methyl malonic aciduria-methyl malonyl CoA
mutase/B12 deficiency
• Propionic academia-propionyl CoA Carboxylase
deficiency
• LCADH Deficiency

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