Exam III 11/30Phospholipid and triacylglycerol synthesis p 166-167,161Cholesterol and bile acidsLipid metabolism in various tissues p 167-170 Cardiovascular Disease Protein and amino acid metabolism p. 184-189; 198-221Protein metabolism in specific tissues p 222-232Assessing protein and amino acid needs p. 237-242Phospholipid and Triacylglycerol Synthesis• Formation of glycerol‐3‐PO4:– From glycerol via glycerol kinase (liver only)– From DHAP (liver and adipose tissue)Formation of Phosphatidic acid:glycerol‐3‐PO4 + 2 fatty acyl‐CoA’s PAPA=converts to diacylglycerol to form lipoproteins and TAGsPhosphatidic acid DiacylglycerolTriacylglycerol PhosphatidylcholineByproduct: CoA CMPAnother way to make phosphatidylcholine (lecithin)Phosphatidylethanolamine + methyl group= PhosphatidylcholineTypes of Phospholipids1. Glycerophosphatides-core structure of glycerol2. Sphingophosphatides-core structure is sphingosineCholesterol: Functions• Component of cell membranes• Synthesis of bile acids• Synthesis of steroid hormones• Precursor for vitamin D (7‐dehydrocholesterol)Cholesterol: Synthesis• Occurs in almost all cells; especially in liver and intestinal cells• Takes place in cytoplasm• Made from acetyl‐CoA• HMG‐CoA is an intermediate (also in ketosis)• Rate‐controlling enzyme: HMG‐CoA ReductaseStructure of Cholesterol Phosphatidic acid OR DiacylglycerolTriacylglycerol PhosphatidylcholineGlycerol-3-PO4 +2 Fatty acyl CoAsGlycerol DHAP-glycerol kinase -liver and adipose-liver only Phosphatidylethanolamine + CH3CoACMPMain ring: Cyclopentanoperhydrophenanthrene Ring-OH group denotes a sterol; not present in steroidsCholesterol Synthesis: Stages• Stage 1:– Synthesis of mevalonate (6 C) from 3 acetyl‐CoA’s• Stage 2:– Formation of isoprene (5 C) by loss of CO2• Stage 3:– Condensation of 6 isoprenoid units to form squaleneStage 4:– Cyclization of squalene to form lanosterol (asteroid)Stage 5:– Formation of cholesterol from lanosterol byremoving 3 methyl groupsStage 12 Acetyl-CoA yields Acetoacetyl-CoAByproduct: CoAAcetoacetyl-CoAHMG-CoAByproduct: CoAHMG yields MevalonateByproduct: NAD+Enzyme: HMG-CoA ReductaseRegulation of HMG‐CoA Reductase• Feedback inhibition (this is not allosteric): inhibited by ↑cholesterol and ↑bile acids• Via covalent modification:– Inactive with PO4– Active without PO4– Favored by insulin– Inhibited by glucagonLower cholesterol by inhibiting HMG‐CoA Reductase: Use statin drugs (e.g. lovastatin)• Increase fecal excretion of bile acids (BAs):– Feed diets high in soluble fiber• Fiber binds BAs; BAs are excreted in feces and not returned to liver• Leads to ↑ cholesterol synthesis, but because the cholesterol must then be used to replace the lost BAs, the net effect is ↓ cholesterol levelsCholesterol Degradation: Routes of Excretion• In feces as:– Unabsorbed cholesterol2 Acetyl CoACoAAcetoacetyl CoaCoAHMG-CoAHMG-CoA Reductase NAD+MevalonateCO2Isoprene6 Isoprenoid unitsSqualeneLanosterol3 methylsCholesterol– Neutral sterols (made from cholesterol)• Converted to bile acidsBile Acids• Synthesized in liver from cholesterol• Major rate‐controlling enzyme: 7α‐hydroxylase• Synthesis regulated by bile acids returned to liver from intestine• May be conjugated with glycine or taurineBile Acids• Primary bile acids: formed in liver– Cholic acid– Chenodeoxycholic acid• Secondary bile acids: formed from primaryBA’s by microbial action in colon– Deoxycholic acid (from cholic acid)– Lithocholic acid (from chenodeoxycholic)Atherosclerotic Plaque Formation A. Endothelial damage 1. Endothelium B. LDL’s penetrate endothelium C. Aggregation of platelets, monocytes & t-lymphocytes 1. Macrophages take up LDLs = foam cells 2. Growth factors released from platelets and macrophages 3. Growth factors stimulate smooth muscle cell growth, and attract more macrophages 4. Smooth muscle cells accumulate LDLs as foam cellsD. Arterial narrowingE. Vessels compensate by vasodilation F. Increased pressure causes cracks in plaque, more endothelial damageG. Platelet aggregation H. Total blockage by plaqueSerum Cholesterol How to modify your cholesterol A.HDL – increase by 1. exercise 2. moderate alcohol intake of red wine B.LDL – decrease by 1. decreasing fat intake 2. Weight loss Amino Acid Metabolism Anabolism-breaks amino acids into: Biogenic amines, peptide hormones, plasma proteins, structural proteins, enzymes, immunoproteins, transport proteinsBasic Structure of Amino Acids H R-C-NH2 amine group Alpha-carbon COOH carboxyl groupEssential Amino Acids*Amino acids that have double bonds-we do not have the enzyme that FORMS the double bonds, therefore, we must get them from our dietValineLeucineIsoleucineThreonineMethioninePhenylalanineTryptophanLysineHistadineConditionally Essential Amino AcidsTyrosineCysteine Proline Arginine GlutamineAminotransferase (Transamination)=transfer of an amino group from an amino acids to an a-keto acidsFunctions:Synthesis of nonessential amino acids (NEAA’s)Degradation of amino acidsRequired Coenzyme:vit. B6 (PLP)Aminotransferase ReactionBasic Reactiona-AA1 + a-keto acid2 PLP Aminotransferasea-keto acid1 + a-AA2 ExampleAlanine + a-ketoglutarate PLP ALT (or SGPT) Pyruvate + Glutamate Pyruvate O O II IICH3 –C-C-OH a Alanine NH2 OII IICH3 - C - C - OH a Aminotransferase Reactions• Amino Acids– alanine – aspartate – glutamate • a-Keto Acids– pyruvate – OAA– a-ketoglutarate Alanine + alpha-Ketoglutaratepyruvate + glutamate-ALTAspartate + alpha-KetoglutarateOAA+ glutamate-ASTALT=alanine aminotransferase-found in liver-concentration increases with trauma or disease to an organindicator of liver damageAlpha-Keto acids (or oxoacids)=contain a carboxylic acid group and a ketone group but NO amino groupBasic StructureCH3 a OO OH-amino acids can be deaminated to produce a-keto acids.-a-keto acids are used as evergy for liver cells and in fatty acids synthesis and also in the liver-In a fasting state, proteins are converted to amino acids, which are then converted in the liver to glucose through gluconeogenesisGlutamine-ammonia transport-NH3/NH4 combine with glutamate to form glutamine-enzyme: glutamine synthase-cofactors: ATP, Mg2+ or
View Full Document
Unlocking...