Glycerol glycerol kinase liver only DHAP liver and adipose Glycerol 3 PO4 2 Fatty acyl CoAs Phosphatidic acid OR Diacylglycerol Phosphatidylethanolamine CH3 CoA CMP Triacylglycerol Phosphatidylcholine Exam III 11 30 Phospholipid and triacylglycerol synthesis Cholesterol and bile acids Lipid metabolism in various tissues Cardiovascular Disease Protein and amino acid metabolism Protein metabolism in specific tissues Assessing protein and amino acid needs p 166 167 161 p 167 170 p 184 189 198 221 p 222 232 p 237 242 Phospholipid 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 PA PA converts to diacylglycerol to form lipoproteins and TAGs Phosphatidic acid Diacylglycerol Triacylglycerol Byproduct CoA Phosphatidylcholine CMP Another way to make phosphatidylcholine lecithin Phosphatidylethanolamine methyl group Phosphatidylcholine Types of Phospholipids 1 Glycerophosphatides core structure of glycerol 2 Sphingophosphatides core structure is sphingosine Cholesterol 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 Reductase Structure of Cholesterol Main ring Cyclopentanoperhydrophenanthrene Ring OH group denotes a sterol not present in steroids Cholesterol 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 squalene Stage 4 Cyclization of squalene to form lanosterol a steroid Stage 5 Formation of cholesterol from lanosterol by removing 3 methyl groups Stage 1 2 Acetyl CoA yields Acetoacetyl CoA Byproduct CoA Acetoacetyl CoAHMG CoA Byproduct CoA HMG yields Mevalonate Byproduct NAD Enzyme HMG CoA Reductase Regulation 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 glucagon HMG CoA Reductase NAD 2 Acetyl CoA Acetoacetyl Coa HMG CoA Mevalonate CoA CoA CO2 Isoprene 6 Isoprenoid units Squalene Lanosterol Cholesterol 3 methyls Lower 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 levels Cholesterol Degradation Routes of Excretion In feces as Unabsorbed cholesterol Neutral sterols made from cholesterol Converted to bile acids Bile Acids Synthesized in liver from cholesterol Major rate controlling enzyme 7 hydroxylase Synthesis regulated by bile acids returned to liver from intestine May be conjugated with glycine or taurine Bile Acids Primary bile acids formed in liver Cholic acid Chenodeoxycholic acid Secondary bile acids formed from primary BA 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 cells D Arterial narrowing E Vessels compensate by vasodilation F Increased pressure causes cracks in plaque more endothelial damage G Platelet aggregation H Total blockage by plaque Serum 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 Basic Structure of Amino Acids H R C NH2 amine group Alpha carbon COOH carboxyl group Amino Acid Metabolism Anabolism breaks amino acids into Biogenic amines peptide hormones plasma proteins structural proteins enzymes immunoproteins transport proteins Essential 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 diet Aminotransferase Transamination transfer of an amino group from an amino acids to an a keto acids Functions Synthesis of nonessential amino acids NEAA s Degradation of amino acids Valine Leucine Isoleucine Threonine Methionine Phenylalanine Tryptophan Lysine Histadine Conditionally Essential Amino Acids Tyrosine Cysteine Proline Arginine Glutamine Required Coenzyme vit B6 PLP Aminotransferase Reaction Basic Reaction a AA1 a keto acid2 PLP Aminotransferase a keto acid1 a AA2 Example Alanine a ketoglutarate PLP ALT or SGPT Pyruvate Glutamate Pyruvate O O II II CH3 C C OH a Alanine NH2 O II II CH3 C C OH a Aminotransferase Reactions Amino Acids alanine aspartate glutamate a Keto Acids pyruvate OAA a ketoglutarate Alanine alpha Ketoglutarate pyruvate glutamate Aspartate alpha Ketoglutarate OAA glutamate ALT AST ALT alanine aminotransferase found in liver concentration increases with trauma or disease to an organ indicator of liver damage Alpha Keto acids or oxoacids contain a carboxylic acid group and a ketone group but NO amino group Basic Structure CH3 a O O OH Glutamine ammonia transport NH3 NH4 combine with glutamate to form glutamine enzyme glutamine synthase cofactors ATP Mg2 or Mn2 occurs in all tissues but mostly muscle and lungs glutamine freely leaves tissues and travels to organs GI tract and immune system rely on glutamine for energy liver and kidney catabolize glutamine to yield glutamate and ammonia ammonia for urea cycle enzyme glutaminase glutamine increases during hypercatabolic conditions Ex Sepsis trauma muscle glutamine release increases glutamine stores become depleted compromises cell function In Kidney 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 gluconeogenesis glutamine is catabolized by renal
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