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![FORMULA FOR CALCULATING ENERGETICS FOR
ODD CHAIN FATTY ACID
• No. of acetyl coA produced= (n-3)/2
No. of Cycles =(n-3)/2
No. of reduced coenzymes= (n-3)/2[ FADH2+NADH]
Remaining 3C is propionyl CoA
For example if 17c fatty acid undergoes beta oxidation
No. of acetyl CoA = 7 { 1 acetylCoA= 12 ATPin TCA}
7×12=84 ATPs
No.of Cycles= 7
No. of reduced coenzymes= 7( FADH2+ NADH)
7(2+3)= 35ATPs
Total no. of ATPs produced= 84+35= 119ATPs
No. of ATPs utilized for activation=2 ATPs
Net gain= 119-2= 117 ATPs
Remaining 3C compound is propionyl CoA which converts to
succinyl CoA and ebters TCA cycel](https://image.slidesharecdn.com/betaoxidationoffattyacids-170328062117/75/Fatty-acid-oxidation-Beta-Alpha-omega-and-peroxisomal-11-2048.jpg)
Uploaded byAnup Shamsher Budhathoki
Fatty acid oxidation ( Beta , Alpha omega and peroxisomal)
1. Beta-oxidation is the major pathway for fatty acid oxidation that occurs in the mitochondria. It involves activation of fatty acids to acyl-CoA derivatives, transport into the mitochondria, and four steps of beta-oxidation to sequentially cleave two-carbon acetyl-CoA units, producing ATP. 2. Minor pathways include alpha-oxidation of phytanic acid in peroxisomes, omega-oxidation of fatty acids in the ER, and peroxisomal beta-oxidation of very long chain fatty acids. 3. Defects in these pathways can cause diseases like Refsum's disease and Zellweger syndrome. Medium chain acyl-CoA
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Introduction to beta-oxidation; major (mitochondrial) and minor (alpha, omega, peroxisomal) types.
Beta-oxidation's function in fatty acid metabolism; stages: activation, transport, and actual oxidation.
Activation of fatty acids to acyl CoA in cytosol; transport mechanism via carnitine shuttle.
Detailed steps of beta-oxidation in the mitochondrial matrix involving oxidation, hydration, and cleavage.
Calculation for ATP yield from even chain fatty acids; example with palmitic acid yields 129 ATPs.
ATP calculations for odd chain fatty acids; example with 17C explaining propionyl CoA fate.
Factors affecting beta-oxidation rate; impact of hormonal regulation via glucagon and insulin.
Overview of alpha, omega, and peroxisomal beta oxidation for fatty acids that cannot undergo beta-oxidation.
Steps of alpha oxidation; significance in metabolizing certain fatty acids; focus on phytanic acid.
Pathophysiology and clinical features of Refsum's disease due to phytanic acid accumulation.
Minor fatty acid oxidation pathway; occurs at omega carbon; functions in defective beta-oxidation.
Oxidation of very long-chain fatty acids in peroxisomes; details on enzyme systems and products.
Various disorders like Zellweger syndrome, MCAD deficiency, and Jamaican vomiting sickness affecting fatty acid metabolism.
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Fatty acid oxidation ( Beta , Alpha omega and peroxisomal)
- 1. 1.Beta- Oxidation 2.Minor fattyacid oxidation Alpha oxidation Omega oxidation Peroxisomal beta oxidation
- 2. Major and minorfatty acid oxidation Major oxidation: Mitochondrial beta oxidation • Minor Oxidation: Alpha oxidation Omega oxidation Peroxisomal Beta oxidation
- 3. Beta- Oxidation Beta–oxidation is defined as the oxidation and splitting of two carbon units at beta carbon atom. This results in sequential removal of 2 carbon fragments as acetyl CoA until the complete oxidation of fatty acids. Beta oxidation occurs almost in all tissues except, erythrocytes and adrenal medulla.
- 4. Stages of beta-oxidation Threemajor steps involved : 1. Preparative stage (Activation of fatty acid) occurs in cytosol. 2. Transport of fatty acyl CoA through carnitine shuttle, present in mitocondrial membrate 3. Beta – oxidation proper in mitochondrial matrix.
- 5. Activation of fattyacid Activation occurs in Cytosol Acyl CoA synthetase / Thokinase Fatty acid Fatty acyl CoA ATP AMP + ppi LCFA requires carnitine shuttle for transport into mitochondrial menbrane SCFA/MCFA do not require carnitine suttle
- 6. Transport of Fattyacyl CoA Acyl CoA Acyl carnitine Acyl carnitine Acyl CoA
- 7. Beta oxidation proper Betaoxidation proper occurs in mitochondrial matrix and involves 4 steps: 1. Oxidation 2. Hydration 3. Oxidation 4. Cleavage
- 8. Steps of Beta–oxidationproper Fatty acyl CoA FAD FADH2 ETC 2 ATP Trans enoyl CoA H2O B- hydroxyacyl CoA NAD NADH ETC 3ATP B –ketoacyl CoA CoA AcylCoA +Acetyl CoA Acyl CoA dehydrogenase Hydratase β- hydroxyacyl CoA dehydrogenase Thiolase Inner Mitochondrial Membrane
- 9.
- 10. FORMULA FOR CALCULATINGENERGETICS FOR EVEN CHAIN FATTY ACID n= Number of carbon atoms present in fatty acid Number of acetyl CoA produced = n/2 Number of cycles for fatty acids= (n/2 -1) Number of reduced coenzyme = (n/2-1) (FADH2 +NADH) For example if 16C (palmitic acid) undergoes beta oxidation No. of acetyl CoA produced= 8 {1 Acetyl CoA = 12 ATP in TCA} 8×12= 96 ATPs No.of cycles for palmitic acid= 7 No.of reduced coenzymes produced= 7( FADH2 + NADH) 7(2+3)= 35 ATPs Total no. of ATPs produced= 96+35= 131 ATPs No. of ATPs utilized during activation= 2 ATPs Net gain= 131-2= 129 (ATPs According to old energeitcs concept)
- 11. FORMULA FOR CALCULATINGENERGETICS FOR ODD CHAIN FATTY ACID • No. of acetyl coA produced= (n-3)/2 No. of Cycles =(n-3)/2 No. of reduced coenzymes= (n-3)/2[ FADH2+NADH] Remaining 3C is propionyl CoA For example if 17c fatty acid undergoes beta oxidation No. of acetyl CoA = 7 { 1 acetylCoA= 12 ATPin TCA} 7×12=84 ATPs No.of Cycles= 7 No. of reduced coenzymes= 7( FADH2+ NADH) 7(2+3)= 35ATPs Total no. of ATPs produced= 84+35= 119ATPs No. of ATPs utilized for activation=2 ATPs Net gain= 119-2= 117 ATPs Remaining 3C compound is propionyl CoA which converts to succinyl CoA and ebters TCA cycel
- 12. β- Oxidation forodd chain fatty acid Beta oxidation for odd chain fatty acid occurs in the same way as for even chain fatty acid except the cleavage step yields propionyl CoA and Acetyl CoA ATP ADP+Pi Fig: -Fate of Propionyl CoA Biotin
- 13. Regulation of beta-oxidation Increased availability of FFA increases the rate of beta oxidation Glucagon increases FFA and Insulin decreases FFA CAT-I is inhibited by Malonyl CoA( substrate for fatty acid synthesis). Thus during denovo synthesis of fatty acid beta oxidation is inhibited
- 14. Minor Fatty acidOxidation Alpha Oxidation Omega Oxidation Peroxisomal Beta Oxidation
- 15. Alpha - oxidation Defined as the oxidation of fatty acid (methyl group at beta carbon) with the removal of one carbon unit adjacent to the α carbon from the carboxylic end in the form of CO2 Alpha oxidation occurs in those fatty acids that have a methyl group(CH3) at the beta-carbon, which blocks beta oxidation. Substrate:-Phytanic acid, which is present in milk or derived from phytol present in chlorophyll and animal fat peroxisomes is the cellular site. No production of ATP
- 16. Steps of alphaoxidation 1. Activation of phytanic acid 2. Hydroxylation 3. Removal of formyl CoA( CO2) 4. Oxidation of Pristanal 5. Beta-oxidation of pristanic acid
- 17. Alpha Oxidation Phytanic acid ATP AMP+ppi Phytanoyl CoA α KG + O2 Succinate +CO2 2-hydroxy phytanoyl CoA Formyl CoA CO2 Pristanal NADP NADPH Pristanic acid Phytanoyl CoA synthetase Phytanoyl CoA Hydroxylase Lyase Aldehyde dehydrogenase
- 18. Pristanic acid undergoesbeta oxidation Pristanic acid Activation Beta oxidation proper 2- methyl propionyl CoA+ 3Acetyl CoA+ 3 Propionyl CoA
- 19. Significance of alphaoxidation Oxidation of methylated fatty acid Production of cerebronic acid which synthesizes cerebroside and sulfatides Production of odd chain fatty acids
- 20. Adult Refsum’s Disease Biochemicaldefect Defect in enzyme phytanoyl CoA hydroxylase( Phytanic acid oxidase) Autosomal reccesive Phytanic acid is acumulated in brain and other tissue lab Findings Plasma Level of phytanic acid > 200µmol/L Normal< 3oµmol/L
- 21. Infantile Refsum’s Disease Biochemicaldefect It is a disorder observed in zellweger syndrome. Congenital peroxisomal biogenesis disorder Lab findings 1. Phytanic acid in the serum is More than 30µmol/L and less than 200µmol/L 2. VLCFA and LCFA in serum is increased
- 22. Molecular Toxicology ofRefsum’s Disease PA is directly toxic to ciliary ganglion cells and induces calcium –driven apoptosis in purkinji cells Recent studies has found that PA has a Rotenone like action in inhibiting complex –I and producing reactive oxygen species This is the reason why neuronal cells and retina rich in mitochondria are prime tissue affected in Refsum’s disease
- 23. Refsum’s Disease Clinicalmanifestations Severe neurological symptoms such as Polyneuropathy, retinitis pigmentosa, Nerve deafness Cerebellar ataxia Patients should avoid intake of diet such as green vegetables and milk.
- 24. Omega(ω) Oxidation Cellularsite: Endoplasmic reticulum oxidation occurs at (ω-omega) carbon—the carbon most distant from the carboxyl group. Substrates : Medium and long chain fatty acid Importance: It is a minor pathway but becomes active when beta oxidation is defective. The product formed are di-carboxylic acid
- 26. Peroxisomal Beta Oxidation Beta oxidation occurs in modified form in peroxisomes. Very Long chain fatty acids (>C22) are often oxidized in peroxisomes. FADH2 produced by the action of Acycl CoA dehydrogenases pass electrons directly to oxygen. This results in formation of H2O2. H2O2 is again cleaved by peroxisomal catalase. Subsequent steps are identical with their mitochondrial counterparts. They are carried out by different isoform of the enzymes.
- 27. Initial step ofPeroxisomal beta oxidation O2 H2O2 H2O+ 1/2O2 Acyl CoA dehydrogenase Acyl CoA dehydrogenase (ox, FAD) (red, FADH2) Fatty acyl CoA Tans enoyl CoA Catalase
- 28. Zellweger syndrome Biochemicaldefect Defect in the gene for peroxisome biogenesis reduction or absence of Peroxisomes in the cells of the liver, kidneys, and brain. VLCFA and LCFA are not oxidized and accumulates in tissue , particularly in brain ,liver and kidney. Lab findings: Increased level of VLCFA in serum Increased level of phytanic acid in serum
- 29. Medium chain acylCoAdehydrogenase deficiency (MCAD deficiency) Most common inborn error of fatty acid oxidation. Being found in 1:14,000 births worldwide. Decreased ability to oxidize fatty acids with six to ten carbons. MCFA accumulates in tissue and also excreted in urine. Symptoms: Hypoglycemia Sleepiness Vomiting Fat accumulation in liver
- 30. Deficiencies of Carnitineor carnitine transferase or carnitine translocase Causes: • Deficiency of carnitine Inherited CPT-I deficiency affects only the liver. CPT-II deficiency affects primarily skeletal muscle and, when severe, the liver. Symptoms: muscle cramps are precipitated by fasting, exercise and high fat diet. Hypoglycemia
- 31. Jamaican vomiting sickness Caused by eating unripe ackee fruit which contains unusal toxic amino acids hypoglycin A and B It inhibits enzyme acyl CoA dehydrogenase . Beta-oxidation is blocked leading to serious complications. Symptoms : Severe hypoglycemia vomiting Convulsions Coma Ackee fruit