Fat/Lipid synthesis Flashcards
Linolenic acid structure
18:3 (9,12,15)
Arachidonic acid structure
20:4 (5,8,11,14)
Triacylglycerol (TAG)
-Storage of energy
- Physiological fat
- 1st Carbon: saturated fat
2nd carbon: unsaturated fat
3rd: saturated or unsaturated fat
Acetyl-CoA Carboxylase (ACC)
-Fatty acid biosynthesis, cytoplasm
Overall: 7 Acetyl CoA + 7 CO2 + 7 ATP –> 7 Malonyl-CoA + 7 ADP + 7 Pi
- Synthesis of palmitate
- Rate-limiting step, irreversible
- ACC has a biotin arm (attached to biotin carrier protein in ACC through lysine) which uses the energy of the ATP to attach to CO2. Then acetyl CoA nucleophilic attacks CO2 to make malonyl CoA
-regulation
Downregulated by glucagon (PKA), adrenaline (PKA), palmitoyl-COA, AMPK (TAMP)
Upregulated by insulin (PP), citrate
-MalonylCoA inhibits FA transport for degradation
Fatty acid synthase (FAS)
- Fatty acid biosynthesis , cytoplasm
- (Complex of many enzymatic activities (6)in one protein + an acyl carrier protein ) x2 –> dimer (two multi reaction chamber)
Contains 6 enzymes: MAT, KS, KR, ER, DH, TE
ACP attaches to the PPE part of coenzyme a. It is the SH of PPE that covalently attaches to acetyl CoA
ATP-citrate lyase
- Breakdown of citrate into Acetyl CoA for FA synthesis (only citrate can be transported into the mitochondria)
- Citrate + CoA + ATP –> OAA + Acetyl-CoA+ ADP + Pi
- OAA is then transformed into malate. Malate is transformed into pyruvate with malic enzyme. There is production of 1NADPH, and pyruvate an go back into the mitochondria
Biotin carboxylase
attached to biotin
- Biotin + CO2 + ATP –> Biotin-CO2 + ADP + Pi.
Then the biotin carrier protein swings the Biotin-CO2 into the transcarboxylase component of ACC
Transcarboxylase
Acetyl CoA+ CO2 (from biotin) –> Malonyl CoA
Malonyl-Acetyl-CoA-ACP transacetylase (MAT)
1st reaction of FAS for FA synthesis
1- acetyl CoA +ACP-SH –> Acetyl-ACP + CoA-SH
2- Malonyl-CoA + ACP-SH –> Malonyl-ACP + CoA-SH
ß-Ketoacyl-ACP-synthase (KS)
2nd step in FAS for FA synthesis
1- acetyl-ACP + KS –> Acetyl-KS + ACP-SH
2- acetyl-KS + malonyl-ACP –> Acetoacetyl-ACP + CO2 + KS
Condensation reaction
ß-ketoacyl-ACP reductase (KR)
3rd step of FAS for FA synthesis.
Acetoacetyl-ACP + NADPH + H+ –> D-Hydroxybutyryl-ACP + NADP
reduction step
ß-hydroxyacyl-ACP dehydrase (DH)
-4th step in FAS for FA synthesis.
D-ß-Hydroxybutyryl-ACP –> å,ß-trans-butenoyl-ACP + H2O
dehydration step
Enoyl-ACP reductase (ER)
å,ß-trans-butenoyl-ACP + NADPH + H+ –> bytyryl-ACP + NADP
reduction step
*use the product 7 times in order to make palmitoyl-ACP
Palmitoylthioesterase (TE)
Palmitoyl-acp +water–> palmitate
Overall reqction for palmitate synthesis
8 Acetyl CoA
Linoleic acid structure
18:2 (9,12)
Overall reaction for palmitate synthesis
8Acetyl CoA + 7ATP + 14 NADPH + 14H+–> 6 H2O + 14 NADP + 7ADP + 7 Pi+ palmitate + 8CoA
Thiokinase
Palmitate + ATP –” Palmitoyl-CoA (is a thioester)+ AMP + PPi
Can be:
- Stored as TAG
- used for energy
- derivatized: elongated or desaturated
3-ketoacyl-CoA synthase
1st reaction in microsomal (Smooth ER) elongation (Major): fatty acid elongation (n+2)
Acyl-CoA (10C and more, sat. or unsat.) + Malonyl CoA –> 3-Ketoacyl-CoA + CoA-SH + CO2
-Condensation reaction.
3-Ketoacyl-CoA reductase
2nd reaction in microsomal elongation
3-D-Ketoacyl-CoA + NADPH + H+ –>3-Hydroxyacyl-CoA + NADP
-Reduction reaction
3-Hydroxyacyl-CoA dehydrase
3rd reaction in microsomal elongation
3-Hydroxyacyl-CoA –> 2-trans-enoyl-CoA + H2O
-Dehydration reaction
2-trans-enoyl-CoA reductase
2-trans-enoyl-CoA + NADPH + H+ –> Acyl-Coa(n+2)
thiolase
1st step in mitochondrial elongation : fatty acid elongation (Minor pathway)
Acyl-CoA + Acetyl CoA –> ß-ketoacylCoA + CoA-SH
3-L-hydroxyacyl-CoA dehydrogenase
2nd step in mitochondrial elongation
ß-ketoacyl-CoA + NADH + H+ –> L-ß-hydroxyacyl CoA + NAD
-reduction reaction
Enoyl-CoA hydratase
3rd step in mitochondrial elongation
L-ß-hydroxyacyl CoA –> a,ß-trans-Enoyl-CoA + H2O
-Dehydration reaction
Enoyl-CoA reductase
4th step in mitochondrial elongation
a,ß-trans-enoyl-CoA + NADPH + H+ –> Acyl-CoA (n+2) + NADP
-Reduction reaction
Generic desaturation of FA in the ER (microsomal)
conditions
Humans have 4 desaturases (give e- to form H2O): ∆9,∆6,∆5,∆4 (count carbonyl as C1)
- y = 7,4,3,2 (must be saturated) (don’t count carbonyl as C1)
- X > or = 5C (can be sat. or unsat.) (don’t count last CH3*)
- Spacing between 2 double bonds (n+3)
*for x and y , count only CH2
Glycerol-P dehydrogenase
1st step TAG synthesis in liver and adipose tissue
-Dihydrocyacetone phosphate + NADH –> Glycerol phosphate
Glycerol kinase
1st step TAG synthesis in liver only
Glycerol + ATP –> Glycerol phosphate + ADP
Acyltransferase
2n, 3rd and 5th reaction of TAG synthesis
2nd: Glycerol phosphate + Acyl-CoA (sat.) –> lysophosphatidic acid + CoA-SH
3rd: Lysophosphatidic acid + Acyl-CoA (unsat.) –> phosphatidic acid (DAG phosphate) + CoASH
5th:
Diacylglycero (DAG) + Acyl-CoA –> Triacylglycerol (TAG) + CoA-SH
phosphatase
4th reaction of TAG synthesis
Phosphatidic acid + H2O –> Diacylglycerol (DAG) + Pi
Carnitine palmitoyl-transferase I
-Fatty acid transport into mitonchondria matrix
fatty acyl CoA + Carnitine –> fattyacyl-carnitine + CoA
-reaction in imm
Carnitine palmitoyl-transferase II
-Fatty acid transport into the mitochondrial matrix
fattyacyl-carnitine + CoA –> Fattyacyl-CoA + carnitine
-reaction in matrix
fatty acyl CoA synthetase
Fatty acid + ATP –> Fatty acyl CoA + AMP + PPi
Acyl-CoA dehydrogenase (AD)
1st reaction of ß-oxidation of fatty acid (occurs in mitochondria)
Fatty acyl-CoA + FAD –> 2-trans-enoyl-CoA + FADH2
*FADH2 electrons transfered to ETC for production of 2ATP
Enoyl-CoA hydratase
2nd step in ß-oxidation of fatty acid
2-trans enoyl CoA + H2O –> 3-hydroxyacyl-CoA
3-Hydroxyacyl CoA dehydrogenase
3rd step in ß-oxidation of fatty acids
3-L-hydroxyacyl-CoA + NAD –> 3-ketoacyl -CoA + NADH + H+
- NADH later used in ETC: produces 3 ATP
ß-ketoacyl CoA thiolase
3-ketoacyl-CoA + CoA –> acyl-CoA (n-2) + acetyl-CoA
- In odd chain FA degradation, the very end product is propionyl CoA (3C)
- Each acetyl CoA provides 12 ATP through the TCA cycle
Summary of the energy yield from the oxidation of palmitoylCoA
14 ATP (from 7FADH2) + 21 ATP (from 7NADH2) + 96 ATP (from 8 acetylCoA) = 131 ATP - 2ATP (for palmitate–> palmitoyl CoA) = 129ATP
propionyl-CoA carboxylase
1st Step for conversion into succinyl-CoA
Propionyl-CoA + HCO3 (biotin) + ATP –> D-Methylmalonyl-CoA + ADP + Pi
methylmalonyl-CoA epimerase
2nd step for conversion into succnyl-CoA
D-Methylmalonyl-CoA L-methylmalonyl-CoA
Methyl-malonyl-CoA mutase
3rd step for conversion into succinyl-CoA
L-Methylmalonyl-CoA + coenzyme B12 succinyl-CoA
succinyl CoA later transformed into OAA then glucose.
Enoyl-CoA isomerase
Degradation of fatty acid with 3,4 C=C bond obstacle
(because only 2,3 trans double bond can be used for ß-oxidation)
3,4 fatty acyl –> 2,3 trans fatty acyl ==> ßoxidation
2,4-dienoyl-Coa reductase
Degradation of FA with 4,5 C=C bond obstacle
(1st: 4,5 C=C fatty acyl + FAD –> 2,4 dienoyl fatty acid (2 db) + FADH2)
2nd: 2,4 dienoyl fatty acyl + NADPH + H+ –> 2,3enoyl fatty acyl + NADP
3,2-enoyl-CoA isomerase
3,2-enoyl fattyacyl –> 2,3 trans fattyacyl ==> ß-oxidation
