BIOL 541 1st Edition Lecture 21 Outline of Last Lecture I. Lipid metabolism Outline of Current Lecture II.Triglyceride synthesisIII. Phospho glyceride synthesisIV. Synthesis of monomer and regulationCurrent LectureBiochem Lecture 21: Triglyceride synthesis:Dihydroxy acetone phosphate from glycolysis is used. There are 2 pathways:A symmetrical pathway is where the central C=O is reduced to form glycerol 3 phosphate. Transfer to fatty acid acyl COA where 2 COA are incorporated at random. Hence, this is called symmetrical pathway.Glycerol kinase phosphorylated in end to form glycerol phosphate, then phosphatase is used where fatty acid is used to make triacyl glycerol. Here specific fatty acid made in specific position and is called asymmetrical pathway. Phospholipase made by this way. Arachodonic acid has bias on 2nd position. Fatty acid is added directly todihydroxy acetone before reduction to position 1. Reduce ketone by using NADPH and 2nd fatty acid added to 1st position and phosphate is hydrolyzed to form lysophosphatidate.Regulation:Enzymes are dimerized. Metabolon where multiple enzymes are grouped together is seen. Glycerol phosphate acyl phosphatase is reglulated by compartments. Endoplasmic reticulum has droplets.These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.The committed step is the last one. The last product phospholipids such as triglycerides are induced by prolactin in mammary glands.Phosphoglyceride synthesis:Leads into membrane lipids which are amphipathic with hydrophobic fatty acid in 1 and 2 position and hydrophobic with polar head group attached at 3 position.Phosphoglycerides:Phosphatidate (glycerol with 2 fatty acids) from triglyceride pathway:Adding head group:Activate and attach to nucleotide CMP primed and replaced SER. Hydroxyl side chain couples SER. (-) charged phosphate group, (-) charged acidic group, and (+) ammine groups are seen. Phosphatidyl SER loses COOH to form ethanolamine which forms phosphatidylethanolamine.H with methyl groups (+) charge is fixed.Donor is S-adenylmethionine where methionine to ribose + sulphur yields sulphur with 3 bonds creating a positive charge (weakened with methyl group as donor).Methyl displaces H and regenerate phosphatidyl ethanolamine to phoaphatidyl choline.This is De Novo pathway where phosphoglycerides are synthesized from scratch.Choline + ethanolamine in diet prefromed head groups used in salvage pathway.Phosphorylated ethanolamine activates nucleotide to form triacyl glycerol. CMP is off to form phosphotidylethanolamine. Choline + phosphate forms CDP-choline which yields phosphocholine.Instead when 2 fatty acids are attached as 1 fatty acid and 1 long chain alcohol, it is called plasmogens.Asymmetrical pathway:1 position is alcohol.Dihydroxy acetone is used as 1 position is open. Fatty acid is added to prime it.Acyl -- Sulphur bond - alcohol.Alcohol is generated in cell organelle called peroxisomes which toxify peroxides.It can also perform alpha oxidation where branched chain fatty acid phytols are broken down to peroxisomes.Reduce acyl COA to alacohol.COOH needs 1. NADH to be converted to aldehyde and 2. NADH is converted to alcohol.Displace fatty acid as ether linkage is formed.Now reduce C=O and add fatty acid to 2nd position.Add head group CDP-ethanolamine.All alcohol are alpha beta unsaturated alcohol which needs double bond which in turn needs NADH. It is bizarre for oxidation to remove H. Molecular oxygenase, O2 accepts H.It is 2 C short, needs NADH and 2 water molecules are formed. Nomenclature- ethanolamine plasmogen (head group, plasmogen).Membrane lipids- where different head groups create different plasmogens. Both phosphoglycerides andplasmogens use glycerol as backbone.Sphingo lipids use amino acid SER as backbone.Amino acid SER has alpha C with COOH, amino group undergoes condensation with palmityl COA.COOH of palmitic acid displaces COOH of SER where loss of CO2 and formation of C-C bond with palmitic acid and SER are seen.Reduce C-C bond with NADPH and form OH to yield dihydroxysphingosine (final product is unsaturated).Add 2nd Fatty acid at amino groups such as amide (peptide bond).Acyl COA does it. SER backbone with palmitic acid C-C bond and 2nd fatty acid is attached as amide bond. Here FAD is H acceptor to form ceramide. There are 3 options :1. Backbone, 2 long hydrophobic chain, need polar head group.Cerebrosides where glucose or galactose is added directly to OH group- no phosphate intervening as in plamogens and no phosphates in cerebrosides.Activated UDP sugar added to OH group.More than 1 sugar, oligosaccharide. Ganglioside where add sugar directly. Cerebroside is in CNS and ganglioside is found in PNS and are membrane neuron rich.2. Phosphotidyl choline which is a source of choline can be formed by attachment to Oh group with phosphate and is done by sphingomyelin synthase. Some platform with 2 long hydrophobic chain and head group enable cell compartments. Hydrophobic chains create a barrier where membrane interacts with polar head groups and aqueous environment.3. Odd one where membrane lipid is cholesterol which is amphapathic with hydrophobic ring structure and polar head out of periphery.Synthesis of polyprenyl pathway:Variety of compounds are formed. Secondary metabolites are compounds that are not critical for life butmay be needed in special cases such as to defend against predation or in reproductive hormones. It is a polymer.Synthesis of monomer and regulation:Monomer is made from 3 acetates. 2 acetyl COA and thiolase split off 1 COA and join them together. 1ST step just like fatty acid synthesis. Aceto acetyl COA is reduced as adding backwards where adding is done on tail. Acetyl COA is transferred to enzymes with CYS. Enzyme transfers on back as tail to form 3 hydroxyl 3 methyl glutaryl. HMG COA synthase is enzyme.Committed step is regulated:Reduce acid to alcohol. 2 NADP is needed for synthetic pathway. 1 NADH is used where acid is converted to alcohol. Mevalonic acid to alcohol is formed where mavalonic acid is added to para phosphate- 1 to other end by using ATP to form mevalonic kinase and phosphor mevalonic ionic kinase to form 5 pyrophosphomevalonic acid.Decarboxylation occurs where loss of CO2 creates a double bond by pyrophosphomevalonate decarboxylase.Iso pentayl phosphate (IPP) is a reaction in equilibrium with 3,3 dimethyl allyl pentyl