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Catabolism of ١lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Steps of β- oxidation 1-activation step in cytosol( endoplasmic reticulium), by using Coenzyme ASH( CoASH) with required energy of two phosphate groups of ATP . ATP→ AMP + PPi PPi→ 2 Pi In the calculation the energy spend in this step is equal two ATP molecules. 2-β- oxidation occurs in the mitochondria matrix after the fatty acid across the mitochondrial membrane, the steps included the following steps: A- oxidation step under influences of fatty acylCoA dehydrogenase which is used FAD as coenzyme,converted into FADH2 and oxidation α- carbon atom and leave double bond. FADH2→ FAD +2 ATP (after oxidation in respiratory chain) B- The product of A, was hydrated with H2O under influence of elonyl-CoA hydratase, the reaction was substitution OH group on β- carbon according Mirkonekoff role( the product was L-β-hydroxy fatty acylCoA , which have OH group can oxidized in the anther step,(this step with out exert energy). ١ Catabolism of ٢lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ C-The OH group was oxidized by NAD+ into β- ketofatty acylCoA , in this step the NADH + H+ produced was oxidized in respiratory chain into NAD+ with 3ATP . D-The final step was cleavage the β-ketofatty acylCoA by thiol group from CoASH in to fatty acylCoA + acetylCoA . The fatty acylCoA was reoxidation by β-oxidation cycles in the mitoconderia with out activation step, AcetylCoA was completely oxidation in TCA cycle. :ﺣﺴﺎﺑﺎت اﻟﻄﺎﻗﺔ اﻟﻤﺘﺤﺮرةﻣﻦ اﻛﺴﺪة ﺑﯿﺘﺎ 2ATP ﺧﻄﻮة اﻟﺘﻨﺸﯿﻂ ﻓﻲ اﻟﺴﺎﯾﺘﻮﺑﻼزم ﺗﺼﺮف 2ATP ﺧﻄﻮة اﻻﻛﺴﺪة اﻻوﻟﻰ ﺗﺤﺮر 3ATP اﻟﺨﻄﻮة اﻟﺜﺎﻟﺜﺔ)ﺧﻄﻮة اﻻﻛﺴﺪة اﻟﺜﺎﻧﯿﺔ( ﺗﺤﺮر 2 \ اﻟﻤﺘﺤﺮرة ﺗﺴﺎوي ﻋﺪد ذرات اﻟﻜﺎرﺑﻮنAcetylCoA ﻋﺪد ﯾﺴﺎوي ﻋﺪدAcetylCoA ﻋﺪد اﻟﺪورات اﻟﻼزﻣﺔ ﻻﻛﺴﺪة اﻟﺤﺎﻣﺾ اﻟﺸﺤﻤﻲ ﻛﻠﯿﺎ اﻟﻰ 1 ﻣﻄﺮوح ﻣﻦ ﻧﺎﺗﺞ اﻟﻘﺴﻤﺔ2 \ ذرات اﻟﻜﺎرﺑﻮن - اﻟﻤﻌﺎدﻟﺔ اﻟﻌﺎﻣﺔ اﻟﻨﺎﺗﺠﺔ ﻣﻦ اﻛﺴﺪة ﺟﺰﯾﺌﺔ اﻟﺤﺎﻣﺾ اﻟﺪھﻨﻲ8 AcetylCoA ﻓﯿﻤﺎ ﯾﻠﻲ اﻟﻤﻌﺎدﻟﺔ اﻟﻤﻌﺒﺮة ﻋﻦ اﻻﻛﺴﺪة اﻟﺘﺎﻣﺔ ﻟﻞ ، ﻓﻲ دورة ﻛﺮﯾﺲPalmitateال ٢ اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ :ﺗﻜﺴﯿﺮ اﻟﺪھﻮن Catabolism of ٣lipids β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ ﻋﺪد اﻟﺪورات ٧اﻟﻼزﻣﺔ ﻟﻸﻛﺴﺪة اﻟﺘﺎﻣﺔ ﻟﺤﺎﻣﺾ اﻟﺒﺎﻟﻤﺘﯿﻚ 18ذرة ﻛﺮﺑﻮن. إذن ﻣﻘﺪار اﻟﻄﺎﻗﺔ اﻟﻨﺎﺗﺠﺔ =5ATP x7 =35ATP ﻣﻘﺪار اﻟﻄﺎﻗﺔ اﻟﻤﺘﺒﻘﯿﺔ = ) اﻟﻄﺎﻗﺔ اﻟﻤﺼﺮوﻓﺔ ﻟﻠﺘﻨﺸﯿﻂ ﻓﻲ اﻟﺴﺎﯾﺘﻮﺑﻼزم (35ATP – 2ATP = 33ATP ﻋﺪد أل Acetyl-CoAاﻟﻨﺎﺗﺠﺔ = 8 ﺑﻌﺪ اﻷﻛﺴﺪة ﻓﻲ دورة ﻛﺮﺑﺲ ﺗﻌﻄﻲ ﻛﻞ اﺳﺘﯿﻞ ﻣﺮاﻓﻖ 12ATP= A إذن ﻣﻘﺪار اﻟﻄﺎﻗﺔ اﻟﻨﺎﺗﺠﺔ ﻣﻦ اﻷﻛﺴﺪة =8X12ATP =96ATP ﻣﺠﻤﻮع اﻟﻄﺎﻗﺔ ﻟﻸﻛﺴﺪة اﻟﺘﺎﻣﺔ ﻋﻠﻰ ھﯿﺌﺔ 33+96= ATP =129ATP اﻟﻄﺎﻗﺔ اﻟﻜﻠﯿﺔ ﻋﻠﻰ ھﯿﺌﺔ 129x(-7.5)= Kcal/mol =-967.5Kcal/mol ٣ Catabolism of ٤lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Beta Oxidation of Odd Carbon Fatty Acids CH 3 CH 2 CH 2 --CH2 CH 2 --CH2 CH 2 --CH2 CH 2 --CH2 CH 2 --CH2 COSCoA 5 Cycles 5 CH3COSCoA + CH3CH2COSCoA Propionyl CoA TCA Cycle Mutase HO 2CCH 2CH 2 COSCoA Succinyl CoA CO2 H Epimerase CH 3 -C-H Vit. B12 COSCoA L-Methylmalonyl CoA Propionyl CoA Carboxylase ATP/CO2 CO2H H-C-CH3 COSCoA D-Methylmalonyl CoA Translocase Carnitine acyltransferase I Carnitine acyltransferase II ٤ Catabolism of ٥lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Ketogenesis: Formation of Ketone Bodies Thiolase 2 CH3COSCoA CH3COSCoA CH3COCH2COSCoA Acetoacetyl CoA HMG CoA Synthase Cholesterol (in cytosol) Several steps See Slide 78 (in liver: mitochondrial matrix) OH HO2C-CH2-C-CH2COSCoA CH3 Ketogenesis -Hydroxy--methylglutaryl CoA (HMG CoA) Ketogenesis: Formation of Ketone Bodies (Cont’d.) OH HO2C-CH2-C-CH2COSCoA CH3 HMG CoA HMG CoA lyase - CH3COSCoA NADH + H+ CH3COCH2CO2 Acetoacetate Dehydrogenase - CO2 NAD+ OH CH3CHCH2CO2 -Hydroxybutyrate Ketone bodies are important sources of energy, especially in starvation ٥ CH3COCH Acetone3 (volatile) Catabolism of ٦lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Ketone Bodies As Energy Sources In liver -Hydroxybutyrate Acetoacetate Acetoacetate is major energy source in cardiac muscle and renal cortex; also in brain in starvation and diabetes Succinyl CoA -Ketoacyl CoA transferase Not found in liver Thiolase 2 Acetyl CoA Acetoacetyl CoA Succinate Combines with oxaloacetate TCA Cycle Fatty Acid Synthesis vs. Degradation Synthesis Intermediates Site Enzymes Redox Coenzymes Linked to SH in Cytosol Components of NADP+ / NADPH ٦ Degradation Linked to CoASH Proteins (Acyl Carrier Proteins) Mitochondria Separate Polypeptides Single Peptide NAD+ / NADH Catabolism of ٧lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Complete Oxidation ﻣﻘﺎرﻧﺔ ﺑﯾن أﻧواع اﻟطﺎﻗﺔ اﻟﻣﺗﺣررة اﻷﻛﺳدة اﻟﺗﺎﻣﺔ 9Kcal/g 4Kcal/g 4Kcal/g :ﻣن اﻷﻧواع اﻟﻣﺧﺗﻠﻔﺔ ﻟﻸﻏذﯾﺔ Fatty acid اﻷﺣﻣﺎض اﻟﺷﺣﻣﺔ Carbohydrates اﻟﺳﻛرﯾﺎت Protein اﻟﺑروﺗﯾن اﻛﺳدة ﺑﯾﺗﺎ ﻻﺣﻣﺎض اﻟﺷﺣﻣﯾﺔ اﻻﺣﺎدﯾﺔ اﻟﻛﺎرﺑون Beta Oxidation of Odd Carbon Fatty Acids CH 3 CH 2 CH 2 --CH2 CH 2 --CH2 CH 2 --CH2 CH 2 --CH2 CH 2 --CH2 COSCoA 5 Cycles 5 CH3COSCoA + CH3CH2COSCoA Propionyl CoA TCA Cycle Mutase HO 2CCH 2CH 2 COSCoA Succinyl CoA CO2 H Epimerase CH 3 -C-H Vit. B12 COSCoA L-Methylmalonyl CoA Propionyl CoA Carboxylase ATP/CO2 CO2H H-C-CH3 COSCoA D-Methylmalonyl CoA ذرة ﻛﺎرﺑﻮن13 اﻟﺤﺎﻣﺾ اﻟﺸﺤﻤﻲ اﻋﻼه ﻣﺘﻜﻮن ﻣﻦ ﯾﺤﺘﺎج ﻟﻼﻛﺴﺪة اﻟﺘﺎﻣﺔ ﺧﻤﺴﺔ دورات PropionylCoA + 5AcetylCoA اﻟﻨﺎﺗﺞ اﻟﻨﮭﺎﺋﻲ اﻟﺬيCarboxylase ﺗﺤﺖ ﺗﺄﺛﯿﺮ اﻧﺰﯾﻢD-MethylmalonylCoA اﻟﻰPropionylCoAﯾﺘﺤﻮل ال . ATP اﻟﻰ ﺟﺰﯾﺌﺔ طﺎﻗﺔCO2 ﯾﺤﺘﺎج دﻣﺞPropionylCoA اﻟﻰCO2 ﯾﻀﯿﻒ ﻣﺠﻤﻮﻋﺔ . Epimerase ﺑﻔﻌﻞ اﻧﺰﯾﻢL اﻟﻰ اﻷﯾﺰوﻣﺮD-MethylmalonylCoA ﯾﺘﺤﻮل ﺗﺪﺧﻞ ﻣﺠﻤﻮﻋﺔ اﻟﻤﺜﯿﻞ ﺿﻤﻦ اﻟﺴﻠﺴﻠﺔ اﻟﻤﺴﺘﻘﯿﻤﺔ ﻟﻠﻌﻤﻮدي اﻟﻔﻘﺮي اﻟﻜﺎرﺑﻮﻧﻲ ﻟﻤﺮﻛﺐ ﺑﻔﻊ ﺗﺄﺛﯿﺮ اﻧﺰﯾﻢ L- وﯾﺘﺤﻮل اﻟﻤﺮﻛﺐB12 )اﻟﺬي ﯾﺴﺘﺨﺪم اﻟﻤﺮاﻓﻖ اﻻﻧﺰﯾﻤﻲ ﻓﯿﺘﺎﻣﯿﻦMutase . TCA cycle اﻟﺬي ﯾﺪﺧﻞ دورةSuccinylCoA اﻟﻰMethylmalonylCoA ٧ اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ :ﺗﻜﺴﯿﺮ اﻟﺪھﻮن Catabolism of ٨lipids β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ ﻛﯿﻔﯿﺔ ﻧﻘﻞ ﻣﺠﻤﻮﻋﺔ ألAcetyl-CoAاﻟﻰ اﻟﺴﺎﯾﺘﻮﺑﻼزم ﻟﻐﺮض ﺗﺨﻠﯿﻖ اﻟﺤﻮاﻣﺾ اﻟﺸﺤﻤﯿﺔ ﻓﻲ اﻟﺴﺎﯾﺘﻮﺑﻼزم ﻻن ال AcetylCoAﻻﯾﻨﺘﻘﻞ ﻣﺒﺎﺷﺮﺗﺎ ﻋﺒﺮﺟﺪار اﻟﻤﺎﯾﺘﻮﻛﻮﻧﺪرﯾﺎاﻟﻰ اﻟﺴﺎﯾﺘﻮﺑﻼزم ﻣﻦ ﺧﻼل ھﺬا اﻟﻤﺨﻄﻂ: ﯾﻌﻤﻞ اﻟﺴﺘﺮﯾﺖ ﺑﻨﻘﻞ AcetylCoAﻣﻦ اﻟﻤﺎﯾﺘﻮﻛﻮﻧﺪرﯾﺎ اﻟﻰ اﻟﺴﺎﯾﺘﻮﺑﻼزم وذﻟﻚ ﻣﻦ ﺧﻼل ارﻧﺒﺎط AcetylCoAﻣﻊ ال Oxaloacetateاﻟﻤﻨﺞ ﻓﻲ اﻟﻤﺎﯾﺘﻮﻛﻮﻧﺪرﯾﺎ ﻣﻜﻮﻧﺎ اﻟﺴﺘﺮﯾﺖ ﺑﺘﺎﺛﯿﺮ ﻓﻌﻞ اﻧﺰﯾﻢ .Citrate synthase ﯾﻌﺒﺮ اﻟﺴﺘﺮﯾﺖ ﻣﻦ ﺣﺸﻮة اﻟﻤﺎﯾﺘﻮﻛﻮﻧﺪرﯾﺎ اﻟﻰ اﻟﺴﺎﯾﺘﻮﺑﻼزﻣﻌﺒﺮ اﻟﺠﺪار اﻟﻤﺎﯾﺘﻮﻛﻮﻧﺪرﯾﺎ اﻟﺨﺎرﺟﻲ. ﯾﺘﺤﻠﻞ اﻟﺴﺘﺮﯾﺖ ﺑﻮﺟﻮد CoAاﻟﻰ OAAو AcetylCoAﺑﻔﻌﻞ اﻧﺰﯾﻢ Lyaseاﻟﺬي ﯾﺤﺘﺎج اﻟﻰ طﺎﻗﺔ اﺻﺮة ﻓﻮﺳﻔﯿﺖ ﻣﻦ ﺗﺤﻠﻞ ﺟﺰﯾﺌﺔ . ATP ٨ Catabolism of ٩lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ ﺗﺨﻠﯿﻖ اﻟﺤﻮاﻣﺾ اﻟﺸﺤﻤﯿﺔ Fatty Acid Biosynthesis ﻣﻘﺎرﻧﺔ ﺑﯿﻦ ﺗﺨﻠﯿﻖ اﻟﺤﻮاﻣﺾ اﻟﺸﺤﻤﺔ وﺗﻜﺴﯿﺮھﺎ ﻣﻦ ﺧﻼل اﻟﻮﺳﻄﯿﺎت اﻟﻤﻮﻗﻊ اﻹﻧﺰﯾﻤﺎت اﻟﻤﺮاﻓﻘﺎت اﻹﻧﺰﯾﻤﯿﺔ ﻟﺘﻔﺎﻋﻼت اﻷﻛﺴﺪة واﻻﺧﺘﺰال Fatty Acid Synthesis vs. Degradation Synthesis Intermediates Site Enzymes Redox Coenzymes Linked to SH in Cytosol Components of NADP+ / NADPH ٩ Degradation Linked to CoASH Proteins (Acyl Carrier Proteins) Mitochondria Separate Polypeptides Single Peptide NAD+ / NADH Catabolism of١٠lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Fatty Acid Biosynthesis: Formation of Malonyl CoA CH3COSCoA + ATP + HCO3 Acetyl CoA Carboxylase - Malonyl CoA O2CCH2COSCoA + ADP + Pi + H+ Committed step in fatty acid synthesis• Reaction is irreversible• Regulation of acetyl CoA carboxylase activity:• by palmitoyl CoA by citrate by insulin by epinephrine and glucagon Malonyl CoA inhibits carnitine acyl transferase I • Blocks beta oxidation • ١٠ اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ :ﺗﻜﺴﯿﺮ اﻟﺪھﻮن Catabolism of١١lipids β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ ١١ اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ :ﺗﻜﺴﯿﺮ اﻟﺪھﻮن Catabolism of١٢lipids β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ اﻟﻤﺴﺎر اﻟﺠﺪﯾﺪ ﻟﺘﺨﻠﯿﻖ اﻟﺤﻮاﻣﺾ اﻟﺸﺤﻤﯿﺔ Denovo pathway of fatty acid biosynthesis ١٢ اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ :ﺗﻜﺴﯿﺮ اﻟﺪھﻮن Catabolism of١٣lipids β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ ﻣﺼﺪر أل NADPHاﻟﻤﺴﺘﺨﺪﻣﺔ ﻛﻤﻜﺎﻓﺌﺎت اﺧﺘﺰاﻟﯿﺔ ﻓﻲ ﺗﺨﻠﯿﻒ اﻟﺤﻮاﻣﺾ اﻟﺸﺤﻤﺔ وھﻲ: ﻣﺴﺎر ال Pentose phosphate pathway ١٣ اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ :ﺗﻜﺴﯿﺮ اﻟﺪھﻮن Catabolism of١٤lipids β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ ﻣﺴﺎر ال Malateاﻟﻰ ال Pyruvate ﻛﻤﺎ ﻓﻲ اﻟﻤﺨﻄﻂ اﻟﺘﺎﻟﻲ Fatty Acid Biosynthesis: Sources of NADPH Pentose Phosphate Pathway: OH O OH OH OP Ribulose-5phosphate NADPH + H+ O CO2- NADP+ OH HO OH OH OP 6-Phosphogluconate CO2 NADPH + H+ OH HO OH OH OP Glucose-6phosphate Malic Enzyme: NADP+ - - HO-CH-CO2 CH3CCO2 Pyruvate NADPH + H+ NADP+ CHO Malic Enzyme CO2 - CH2CO2 Malate اﻟﻌﻼﻗﺔ اﻟﺪاﺧﻠﯿﺔ ﺑﯿﻦ اﻟﻜﻠﻮﻛﻮز وﺗﺨﻠﯿﻖ اﻟﺤﺎﻣﺾ اﻟﺸﺤﻤﻲ ﻣﻦ ﺧﻼل اﻟﻤﺨﻄﻂ اﻟﺘﺎﻟﻲ ﻓﻲ اﻟﺴﺎﯾﺘﻮﺑﻼزم ﺗﺴﺘﺨﺪم ال NADH +H+اﻟﻨﺎﺗﺞ ﻣﻦ ﺗﺤﻠﻞ اﻟﻜﻠﻮﻛﻮز Glycolysisﻓﻲ اﺧﺘﺰال ال ) Oxaloacetateاﻟﻘﺎدم ﻣﻦ اﻟﻤﺎﯾﺘﻮﻛﻮﻧﺪرﯾﺎﺑﻌﺪ طﺮح ال (AcetylCoAاﻟﻰ Malate اﻟﺬي ﯾﺘﺤﻮل اﻟﻰ Pyruvateﺑﻌﺪ طﺮح CO2ﺑﺎﺳﺘﺨﺪام ﻣﻜﺎﻓﯿﺊ اﻻﻛﺴﺪة NADP+اﻟﺬي ﯾﺘﺤﻮل اﻟﻰ NADPH+H+اﻟﺬي ھﻮ اﻻﺧﺮ ﯾﺴﺘﺨﺪم ف.ي ﻋﻤﻠﯿﺎت اﻻﻛﺴﺪة ﻓﻲ ﻣﺮاﺣﻞ ﻟﺘﺨﻠﯿﻖ اﻟﺤﺎﻣﺾ اﻟﺸﺤﻤﻲ . ﯾﺪﺧﻞ ال Pyruvateاﻟﻰ اﻟﻤﺎﯾﺘﻮﻛﻮﻧﺪرﯾﺎ ﻣﺘﺤﻮﻻ ﻓﻲ دورة ﻛﺮﺑﺲ اﻟﻰ Citrateاﻟﺬي ﯾﺴﺘﻄﯿﻊ ﻋﺒﻮر ﺟﺪار اﻟﻤﺎﯾﺘﻮﻛﻮﻧﺪرﯾﺎ اﻟﻰ اﻟﺴﺎﯾﺘﻮﺑﻼزم. ١٤ اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ :ﺗﻜﺴﯿﺮ اﻟﺪھﻮن Catabolism of١٥lipids β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ ١٥ Catabolism of١٦lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Fatty Acid Biosynthesis: Chain Elongation CH3CH2CH2CO-S-ACP - + O2CCH2CO-S-ACP CH3CH2CH2COCH2CO-S-ACP H OH CH2CH2CH2CHCH2CO-S-ACP CH3CH2CH2C=CCO-S-ACP H Fatty Acid Biosynthesis: Chain Elongation (Cont’d) H NADPH + +H CH3CH2CH2C=CCO-S-ACP CH3(CH2)3CH2CO-S-ACP H CH3(CH2)13CH2CO2 Palmitate + NADP 5 Cycles - CH3(CH2)13CH2CO-S-ACP Thioesterase ١٦ Palmitoyl ACP Catabolism of١٧lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Fatty Acid Biosynthesis: Fatty Acid Synthase in Animals Consists of a single polypeptide containing • three distinct domains Conducts all steps in fatty acid synthesis• except function of acyl CoA carboxylase Further Processing of Fatty Acids: Elongation CH3(CH2)13CH2COSCoA Palmitoyl CoA In mitochondria and at surface of endoplasmic reticulum CH3COSCoA Thiolase CH3(CH2)13CH2COCH2COSCoA NADH + H+ NAD+ Dehydrogenase OH L- Configuration CH3(CH2)13CH2CCH2COSCoA H ١٧ Catabolism of١٨lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Further Processing of Fatty Acids: Elongation (Cont’d) OH CH3(CH2)13CH2CCH2COSCoA H - H2O Hydratase H CH3(CH2)13CH2C=CCOSCoA NADPH + H+ Dehydrogenase H NADP+ CH3(CH2)13CH2CH2CH2COSCoA Stearoyl CoA Further Processing of Fatty Acids: Unsaturation CH3(CH2)13CH2CH2CH2COSCoA Stearoyl CoA O2 Stearoyl CoA Desaturase CH3(CH2)7C=C(CH2)7COSCoA + H2O Oleoyl CoA H H This reaction occurs in eukaryotes Endoplasmic reticulum membrane ١٨ Catabolism of١٩lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Cholesterol Biosynthesis: Formation of Mevalonate Liver is primary site of cholesterol biosynthesis Thiolase 2 CH3COSCoA CH3COCH2COSCoA Acetoacetyl CoA OH HMGCoA reductase HO2C-CH2-C-CH2CH2OH CH3 HMG CoA Synthase OH HO2C-CH2-C-CH2COSCoA CoASH NADP + NADPH 3R-Mevalonic acid CH3COSCoA CH3 + H+ -Hydroxy--methylKey control step glutaryl CoA (HMG CoA) in cholesterol biosynthesis Cholesterol Biosynthesis: Processing of Mevalonate OH - O2C-CH2-C-CH2CH2OH CH3 Mevalonate OH 2 Steps -O2C-CH2-C-CH2CH2OPOP ATP CH3 5-Pyrophosphomevalonate - CO2 - H2O CH3 Isomerase CH3-C=CH2CH2OPOP CH2=C-CH2CH2OPOP Isopentenyl Dimethylallyl CH3 pyrophosphate pyrophosphate ١٩ Catabolism of٢٠lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Cholesterol Biosynthesis: Isoprenoid Condensation Dimethylallyl pyrophosphate Tail Head to tail Condensation OPOP OPOP Tail Head Head H Tail OPOP Geranyl transferase Isopentenyl Pyrophosphate (IPP) Geranyl Pyrophosphate (GPP) Isoprenes Geranyl transferase Tail to tail condensation of 2 FPPs Squalene synthase Squalene Head Head to tail condensation of IPP and GPP OPOP Head Tail Farnesyl Pyrophosphate (FPP) Isoprenoids Widely distributed in nature• Generally contain multiple of 5 carbons:• Monoterpene; 10 carbons• Sesquiterpene: 15 carbons• Diterpene: 20 carbons• OH OH Menthol: a monoterpene Lycopene: a tetraterpene ٢٠ Catabolism of٢١lipids ﺗﻜﺴﯿﺮ اﻟﺪھﻮن:اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ Conversion of Squalene to Cholesterol Squalene2,3-epoxide Squalene monooxygenase O2 O Squalene 2,3-Oxidosqualene cyclase H+ CH3 CH3 CH3 20 Steps CH3 CH3 HO HO H3C CH3 Cholesterol Acyl-CoA: cholesterol acyltransferase Lanosterol CH3 RCO2 Cholesterol esters (principal transport form in blood) Transformations of Cholesterol: Steroid Hormones OH CH3 O O OH HO CH3 O HO Cortisol Cholesterol O Progesterone OH OH OH O Testosterone HO CH 2 Estradiol HO OH Vitamin D ٢١ اﻟﻤﺤﺎﺿﺮة اﻟﺜﺎﻧﯿﺔ :ﺗﻜﺴﯿﺮ اﻟﺪھﻮن Catabolism of٢٢lipids β-Oxidation of Fatty Acids اﻻﺳﺘﺎذ اﻟﺪﻛﺘﻮر ﻋﻮده ﻣﺰﻋﻞ ﯾﺎﺳﺮ اﻟﺰاﻣﻠﻲ ٢٢
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