Biochimica II – Lezione 11 – Slides

Vie cataboliche Trigliceridi Fosfolipidi

Acetil-CoA Acidi Grassi Corpichetonici Ciclo Di Krebs Colesterolo CO2 CO2 ACPL' acetil - CoA viene formato nel mitocondrio La biosintesi degli acidi grassi avviene nel citoplasma L' acetil - CoA deve essere trasportato nel citoplasma! Aminoacidi + ATP Citrate liase Citrate Oxalacetate Piruvato deidrogenasi synthase Malatedeidrogenase Piruvato Piruvatecarboxylase Malic enzyme Glicolisi Glucosio 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
• Cys = Cisteina del la -Chetoaci l-sintasi

BIOSINTESI DEGLI ACIDI GRASSI Pant = Fosfopanteteina Malonil transf erasi Acetil transferasi HS-CoA HS-CoA Ace til-CoA Ma lonil-CoA -Chet oacil-ACPβ sint asi CO2 -Idrossiacil-ACPβ Enoil- ACP deid ratasi -Chetoacil-ACPβred utt

asi redut tasiSH β-SH -SH
Further Processing of Fatty Acids:
Elongation In mitochondria and
CH (CH ) CH COSCoA at surface of
C16 3 2 13 2 endoplasmic reticulum
Palmitoyl CoA CH COSCoA
3Thiolase
CH COSCoA
CH (CH ) CH CO 23 2 13 2
+NADH + H Dehydrogenase
+NAD OH β L-Configuration
CH COSCoA
CH (CH ) CH C 23 2 13 2 H
Further Processing of Fatty Acids:
Elongation
OH
CH COSCoA
CH (CH ) CH C 23 2 13 2 H
- H O2dehydratase H CCOSCoA
CH (CH ) CH C=3 2 13 2
+NADPH + H HDehydrogenase ++NADP
C18 CH COSCoA
CH (CH ) CH CH 23 2 13 2 2
Stearoyl CoA
Further Processing of Fatty Acids:
Unsaturation
CH (CH ) CH CH CH COSCoA
3 2 13 2 2 2
Stearoyl CoA Stearoyl CoA
O 2 Desaturase
C=C(CHCH (CH ) ) COSCoA + H O
C=C3 2 7 2 7 2
Oleoyl CoA HH
This reaction occurs in eukaryotes
Endoplasmic reticulum membrane
Further Processing of Fatty Acids:
Polyunsaturation
9CH (CH ) C=C(CH ) CO H Oleic acid
3 2 7 2 7 2 ∆9(18:1 )
H H Animals: Further unsaturation
Plants: Further unsaturation occurs primarily in this region
occurs primarily in this region
12

9 CO H2∆9, 12Linoleic acid (18:2 )Essential dietaryfatty acids in mammals

15 12 9 CO H2∆9, 12, 15Linolenic acid (18:3 )Formation of Arachidonatein Mammals

CO H2Linoleic acid As CoA ester:1) Elongation2) Desaturation x 214 11 8 5 CO H2∆5, 8, 11, 14Arachidonic acid (20:4 )(Eicosa-5,-8,11,14-tetraenoic acid)Prostaglandins

Omega-3 Fatty Acids CO H2∆5, 8, 11, 14, 17ω-3 Eicosapentaenoic acid (20:5 )double bond CO H2∆4, 7, 10, 13, 16, 19Docahexaenoic acid (22:6 )Found in fish oils, esp. cold water fish• Important in:• Growth regulationModulation of inflammationPlatelet activationLipoprotein metabolismVie cataboliche Trigliceridi FosfolipidiAcetil-CoA Acidi GrassiCorpichetoniciCicloDi Krebs ColesteroloCO 2CO 2Metabolite Regulation of Fatty AcidSynthesis and BreakdownCitrateGlucose Stimulates Blocks BetaPyruvate Acetyl CoA Malonyl CoA OxidationInhibitsPalmitoyl CoAHormonal Regulation of Fatty AcidSynthesis and BreakdownPhosphodiesteraseAdenylyl cyclaseATP cAMP

AMP Stimulates Insulin

Glucagon and Inactivates epinephrine Activates Protein Kinase lipase

Inhibition of Activates triacyl- Inactivates ACC by fatty acid glycerol lipase phosphorylation synthesis

Biosintesi dei TRIGLICERIDI E DEI GLICEROFOSFOLIPIDI

Tessuti extraepatici Fegato

Fegato Sintesi dei GLICEROFOSFOLIPIDI

Lo schema indica solo le reazioni formali. Le biosintesi invece procedono con diverse strategie

Strategie per la biosintesi dei Fosfogliceridi

Batteri Eucarioti

Biosintesi della cardiolipina nei batteri

Biosintesi del Biosintesi della fosfatidil- inositolo cardiolipina negli eucarioti

Biosintesi dellafosfatidil-etanolamina

Biosintesi dellafosfatidil-etanolamina

Biosintesi dellafosfatidil- colina

Biosintesi dellafosfatidil- colina (altra strategia)