中南大学 生物化学 考研课件 ch25 脂类生物合成 lipid biosynthesis06.ppt

1、Biochemistry,For Speciality of Biotechnology or Bioengineering at CSU Mr. XIA Jinlan,Chapter 25 Lipid biosynthesis,Fatty acid synthesis,Synthesis of saturated fatty acids,Synthesis and degradation of fatty acids take place in different places,Differences between fatty acid breakdown and synthesis,Sa

2、turated fatty acid-CoA,The general reaction (for palmitic acid synthesis),Alternatively expressed as:,Fatty acid is synthesized from acetyl-CoA in cytosol,In one word:,Where does the acetyl-CoA come from and how does it transfer ?,Cytosol Acetyl-CoA,Amino acid degradation,Mitochondrion Acetyl-CoA,Fa

3、tty acid oxidation,Glycolysis,Pyruvate,cytosol,Required,cytosol,MT,MT,MT: mitochondrion,Citrate-malate-pyruvate shuttle,Why is malonyl-CoA needed ? How does it commonly form ?,The first step is to form acetyl- and ,malonyl-acyl carrier protein,Acetyl transacylase is not highly specific, but not at m

4、uch lower rates; malonyl transacylase is just contrary.,Structures of ACP and CoA (CoASH),Acetyl-CoA carboxylase is Biotin-dependent and displays ping-pong kinetics,The carboxylation of biotin,The transcarboxylation of biotin,The carboxylation of acetyl-CoA,In animals, acetyl-CoA carboxylase is a mu

5、ltifunctional protein,The ACCase Is modulated by phosphorylation and dephosphorylation,P808 Also see p819,More active form,Then, how does the fatty acid chain elongate and Is there also a common cycle ?,The elongation cycle of fatty acid synthesis,The final product of fatty acid synthesis,Total cycl

6、es: 7,The initial and continuation reaction of fatty acid synthesis,For the further synthesis of C16 fatty acids, how does it process ?,Catalyzed by enzymes on smooth ER (SER) Malonyl-CoA, rather than malonyl-ACP as the two-carbon donor Elongated chain as CoA derivative rather than ACP derivative,Ad

7、ditional elongation,In ER,How is the fatty acid synthesis regulated ?,The key enzyme: acetyl-CoA carboxylase (ACC),Regulation of ACC,Short-term effects Citrate activites ACC polymerization Long-chain fatty acids inhibit ACC Insulin stimulates de-phosphorylation and activation Glucagon stimulates pho

8、sphorylation and inhibition 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, fast

9、ing and glucagon lead to decreased synthesis,Summary of the control of acetyl CoA carboxylase by Phosphorylation and allosteric regulation,Key enzyme: Acetyl CoA carboxylase,Homework,1, 2, 11 p850,Fatty acid synthesis,Synthesis of unsaturated fatty acids,Appendix:,Biosynthesis of monounsaturated fat

10、ty acids follows distinct routes in E. coli and animal cells Anaerobic pathway厌氧途径 for E. coli Aerobic pathway好氧途径 in Eukaryotes Biosynthesis of polyunsaturated fatty acids occurs mainly in Eukaryotes,Anaerobic pathway for E. coli,Aerobic pathway for Eukaryotes,Biosynthesis of polyunsaturated fatty

11、acids occurs mainly in Eukaryotes,Mammals can desaturate only between the 9 position and the carboxyl end of an acyl chain Unable to synthesize linoleic acid (亚油酸18 : 2 9, 12 ) and linolenic acid (亚麻酸18 : 3 9, 12, 15 ) Take only from diet-essential fatty acids Starting points for synthesis of other unsaturated fatty acids, such as arachidonate 花生四烯酸 (C20:4)，a precursor of several biologically important molecules, e.g., prostaglandins前列腺素 etc., Plants have the enzymes to desatu