中南大学 生物化学 考研课件 ch25 脂类生物合成 lipid biosynthesis

-
O O C CH2
O C ACP
Six cycles
Total cycles: 7
O STOP AT CH3(CH2)14C ACP Thioesterase O CH3(CH2)14C OH Palmitate 软脂酸或棕榈酸 Palmitoyl-ACP 软脂酰 -ACP
ACP
The initial and continuation reaction of fatty acid synthesis
The carboxylation of biotin
The transcarboxylation of biotin
In animals, acetyl-CoA carboxylase is a multifunctional protein
More active form
The ACCase Is modulated by phosphorylation and dephosphorylation
Structures of ACP and CoA (CoASH)
H CH3
HO C
CH2 CH2
NH C C C
CH2 OH
NH2
-
O
O OH CH3
Pantothenic acid 泛酸
OH CH3 HS CH2 CH2 NH C CH2 CH2 O NH C C C O H CH3 O O O P O CH 2 O P O
Enoyl-ACP reductase
O C ACP
NADPH + H+ NADP+
Crotonyl-ACP 巴豆酰 -ACP
H
O H3C CH2 CH2 C ACP
Butyryl-ACP 丁酰 -ACP
The final product of fatty acid synthesis
O H3C CH2 CH2 C ACP

Biosynthesis of monounsaturated fatty acids follows distinct routes in E. coli and animal cells
CH2 O P O
O CH2 Ser ACP
CH 3
Pantothenic acid
b-Mercaptoethy lamine
ACP
or HS-ACP
The carboxylation of acetyl-CoA
Acetyl-CoA carboxylase is Biotindependent and displays pingpong kinetics

Phosphorylation by AMP-regulated kinase which itself is phosphorylated and activated by a kinase kinase, PKA phosphorylates PPI-1 leading to reduced phosphate removal from ACC

Long-term effects

High carbo and fat-free diets lead to increased synthesis high-fat diets, fasting and glucagon lead to decreased synthesis
Key enzyme: Acetyl CoA carboxylase
Additional elongation
In ER
How is the fatty acide key enzyme: acetyl-CoA carboxylase (ACC)
Regulation of ACC

Short-term effects
O C ACP Malonyl-ACP 丙二酸单酰 -ACP
Acyl-malonyl-ACP condensing enzyme
ACP + CO 2
O H3C C CH2
O C ACP
NADPH + H+ NADP+
Acetoacetyl-ACP 乙酰乙酰 -ACP
The elongation cycle of fatty acid synthesis
Biochemistry
For Speciality of Biotechnology or Bioengineering at CSU Mr. XIA Jinlan
Chapter 25 Lipid biosynthesis
Fatty acid synthesis
Synthesis of saturated fatty acids
AMP ATP AMP-activated protein kinase
ATP
ADP
P
Citrate
P
Active carboxylase Pi
Protein H2O phosphatase 2A Glucagon Epinephrine Insulin
Inactive carboxylase
Palmitoy l Partially active CoA carboxylase
Degradation
M ITOCHONDRION
Differences between fatty acid breakdown and synthesis
Breakdown Site of actions Role of NADPH or NADH Linkage of Fatty acid Use of enzyme(s) Cytosol for prokaryotes Mitochondria for eukaryotes NADH produced in boxidation Fatty acid-CoA Synthesis Cytosol for both prokaryotes and eukaryotes Use NADPH as the reductant Fatty acid-acyl carrier protein Separate enzymes for plants and bacteria Single multifunctional enzyme complex-fatty acid synthase for animals

Citrate activites ACC polymerization Long-chain fatty acids inhibit ACC Insulin stimulates de-phosphorylation and activation Glucagon stimulates phosphorylation and inhibition
Reduction 还原
b-Ketoacyl-ACP
reductase
O H3C CH CH2 OH Dehydration 脱水
3-Hydroxyacyl-ACP dehydratase H2O
C ACP
D-3-Hydroxy-butyryl-ACP D-3- 羟基 - 丁酰 -ACP
H H3C C C Reduction 还原
The first step is to form acetyl- and ,malonylacyl carrier protein
HCO3ATP Pi ADP
O CH3
ACP CoA Acetyl transacylase
O
-
O C CH2 C SCoA
ACP
C SCoA
Acetyl CoA carboxylase
P808 Also see p819
Then, how does the fatty acid chain elongate and Is there also a common cycle ?
O Acetyl-ACP CH 3 乙酰 -ACP Condensation 缩合 C ACP
-
O O C CH2
Synthesis and degradation of fatty acids take place in different places
Synthesis
CYTOSOL C4 CO2 Malonyl CoA CO2 Acetyl CoA Pyruvate C16 C14 C12 Acetyl CoA C4 Ketone bodies To TCA cycle C6 C8 C10 Mit ochondrion membrane C6 C8 C10 C12 C14 Fatty acid
Several individual separate enzymes
The general reaction (for palmitic acid synthesis)
O 8 CH3CCoA + 7 ATP + 14 NADPH + 7 H
Acety l-CoA 乙酰-CoA
4+
CH3(CH2)14COCoA + 7 CoASH + 14NADP + 7 ADP + 7 Pi
O
Malonyl transacylase
CoA
O CH3 C ACP
-
O O C CH2
O C ACP
Acetyl-ACP 乙酰 -ACP
Malonyl-ACP 丙二酸单酰 -ACP
Acetyl transacylase is not highly specific, but not at much lower rates; malonyl transacylase is just contrary.
Palmitic acid-CoA 棕榈酰-CoA