HUN3224 Exam 3 Study Guide 1 Beta Oxidation and Ketosis p 157 160 Phospholipid and triacylglycerol synthesis Cholesterol and bile acids Lipid metabolism in various tissues Cardiovascular Disease p 166 167 161 p 166 166 167 16 p 167 170 Protein and amino acid metabolism Protein metabolism in specific tissues Assessing protein and amino p 184 189 198 221 p 222 232 p 237 242 acid needs Beta Oxidation and Ketosis Beta Oxidation Advantages of using fat as fuel o More energy per gram than CHO o Very large storage capacity Disadvantages of using fat as fuel o Slower mobilization lower enzymatic activity than CHO o Can t be used as anaerobic fuel FFA must be bound to albumin for transport in the blood Oxidation A series of reactions whereby the H s are removed and 2 Carbon units of the FA are split off in the form of acetyl CoA o Occurs in the mitochondria o Aerobic o No major rate controlling enzyme o End products Acetyl CoA NADH H FADH2 Stages o Fatty acid from glycolysis will bind to Albumin goes to tissues where Oxidation occurs Fatty acid must be activated attached to CoA before they can be oxidized This uses 2 ATP s HUN3224 Exam 3 Study Guide 2 o FA s must go from cytoplasm to mitochondria by carnitine Carnitine synthesized from lysine and methionine therefore not essential In high concentrations in the muscle Supplementation and athletic performance 1 Intake of carnitine supplements in body does not prove an increase in beta oxidation studies are not conclusive 2 Studies at low intensity however imply that carnitine supplements should increase beta oxidation because glycogen is spared CPT 1 will transfer carnitine to Acyl CoA will be released Once FA is bound to carnitine carnitine acyl carnitine transferase moves FA bound to carnitine to mitochondria As it brings it into the mitochondria 1 carnitine molecule must be pumped out CPT 2 will bind CoA to FA which will release carnitine into mitochondria CoA coming from krebs cycle Once FA is attached to CoA in mitochondria beta oxidation can occur We continue cleaving until last 4C unit is left this is realistically 2C 2C so it is 2 molecules of Acetyl CoA already cleavage not necessary Beta oxidation energetics o Example Palmitic Acid 16C saturated FA 16C s 8 Acetyl CoA b c 2C s cleaved off each time to form Acetyl CoA 7 NADH H and 7 FADH2 number of NADH and FADH usually of Acetyl CoA minus 1 this is because we cleave the 16C unit 7 times Each NADH H 3ATP so 7x3 21 ATP Each FADH2 2ATP so 7x2 14 ATP The 8 Acetyl CoA go to krebs cycle giving 12 ATP per Acetyl CoA so 8x12 96 ATP HUN3224 Exam 3 Study Guide 3 Total 21 14 96 131 ATP But we used 2 ATP to activate the fatty acid so 131 2 129 ATP TOTAL For every double bond you expend 2 ATP s to break so if she states how many DB s or that it is unsaturated deduct 2 ATP s from total number for every double bond If there is an odd number of Carbons only oxidized until 3C so final products are 2C propionyl CoA Propionyl CoA is converted to Succinyl CoA which enters TCA cycle o o Regulation of Beta oxidation o Enhanced by Fasting epinephrine and glucagon favored Uncontrolled diabetes Hormones which increase cAMP glucagon epinephrine Endurance training Inhibited by Malonyl CoA o High levels during fat synthesis o o carnitine setup Inhibits fat translocation into mitochondria Fed State Disease states that lead to carnitine deficiency and deficiencies of B oxidation enzymes can lead to hypoglycemia Ketone Bodies Ketone body formation o Made in the liver however the liver cannot metabolize them o o Consists of 3 compounds Intermediate is HMG CoA also an intermediate in cholesterol synthesis o Occurs during conditions when fat oxidation is overly active leads to an accumulation of Acetyl CoA Acetoacetate Hydroxybutyrate Acetone Starvation Fasting Severe prolonged exercise Uncontrolled diabetes Very high fat diet low CHO o Because Acetyl CoA is present in larger amounts than OAA the extra Acetyl CoA is used to produce ketones in the mitochondria and the liver Function of ketone bodies o Used for energy by extrahepatic tissues ex muscle by brain during adapted starvation o In extrahepatic tissues ketone bodies are converted back into Acetyl CoA TCA cycle to produce energy o Therefore ketone bodies can be used as a source of energy when CHO is low and helps to conserve blood glucose HUN3224 Exam 3 Study Guide 4 DHAP Glycerol Via G 3 PO4 dehydrogenase via glycerol kinase Glycerol 3 PO4 2 Fatty acyl CoAs Phosphatidic acid Diacylglycerol Triacylglycerol Phosphatidylcholine CoA CMP Phospholipid and Triacylglycerol Synthesis Formation of glycerol 3 PO4 From glycerol via glycerol kinase liver only o o From DHAP liver and adipose tissue o Glycerol 3 PO4 2 fatty acyl CoA s PA Formation of Phosphatidic acid PA Phosphatidic Acid A common intermediate in phospholipid and triglycerol synthesis Another way to make phosphatidylcholine lecithin Phosphatidylethanolamine Add methyl group CH3 via SAM 3x Phosphatidylcholine CH3 o SAM s adenosyl methionine molecule that donates Types of Phospholipids according to nitrogenous base o Phosphatidylcholine o Phosphatidylethanolamine o Phosphatidylinositol o Phosphatidylserine Cholesterol and Bile Acids Cholesterol Functions of Cholesterol Synthesis o Component of cell membranes o Synthesis of bile acids o Synthesis of steroid hormones o Precursor for vitamin D 7 dehydrocholesterol o Occurs in almost all cells especially in liver and intestinal cells o Takes place in cytoplasm o Made from acetyl CoA o HMG CoA is an intermediate also in ketosis o Rate controlling enzyme HMG CoA Reductase o Cyclopentanoperhydrophenanthrene Ring Structure of Cholesterol OH group denotes a sterol not present in steroids HMG CoA Reductase NAD HUN3224 Exam 3 Study Guide 5 2 Acetyl CoA Acetoacetyl Coa HMG CoA Mevalonate CoA CoA CO2 Isoprene 6 Isoprenoid units Squalene Lanosterol Cholesterol 3 methyls Cholesterol Synthesis Stages o Stage 1 Synthesis of mevalonate 6 C from 3 acetyl CoA s HMG CoA Mevalonate is the rate limiting step o Requires NADPH H o Enzyme HMG Reductase o Stage 2 Formation of isoprene 5 C by loss of CO2 Isoprene formed first from phosphorylation of mevalonate from ATP then for decarboxylation mevalonate loses a carbon o Stage 3 Condensation of 6 isoprenoid units to form squalene Isomerization of isoprene followed by condensation to another isoprene molecule until 30 C units are put together to make squalene o Stage 4 Cyclization of squalene to form lanosterol a steroid o Stage 5
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