Physiology Unit 1 METABOLISM OF LIPIDS AND PROTEINS

Physiology Unit 1 METABOLISM OF LIPIDS AND PROTEINS

Alternate Fuel Sources When glucose levels are low Proteins and Triglycerides will be metabolized Tissues will use different fuel sources depending on: The metabolic activity of the tissue Fuel sources available Diet Fasting

Proteins Proteins are digested to amino acids in the stomach and small intestine by proteases Amino acids used to: Make ATP Biosynthesis Non-essential amino acids Metabolic intermediates Glucose Fats Intracellular proteins

Amino Acids

Amino Acids as Fuel Glucogenic Amino Acids Amino acids converted to α keto acids (pyruvate) Pyruvate Converted to glucose Occurs in the liver Production increases during catabolysis (fat and muscle tissue breakdown) Produced by transamination and oxidative deamination Ketogenic Amino Acids Amino acids degraded to acetyl-coa Produced by oxidative deamination Acetyl-CoA: Is the precursor of ketones Used to make fatty acids Used to make ATP Can not be converted to glucose (WHY?)

Transamination Make another type of amino acid by transferring an amine (NH 2 ) from an existing amino acid to a keto acid Example An amine group is transferred from L-alanine to α-ketoglutarate to make pyruvate and L-glutamate Amine group is BLUE

Oxidative Deamination Glutamate is commonly deaminated to α-ketoglutarate by glutamate dehydrogenase (GDH) The amine (NH 2 ) from an amino acid is removed (deamination) Oxygen replaces the nitrogen Oxygen comes from splitting H 2 O The removed amine group gives rise to NH 3 (then to urea) The product is a α keto acid and/or a ketone Occurs mostly in the liver and kidneys

Keto Acids α keto acid Pyruvate Many fates Oxaloacetate Kreb s Cycle intermediate α-ketoglutarate Kreb s Cycle intermediate Coenzyme function in cell signaling Commonly used in transamination reactions β keto acid Acetoacetate A ketone released from the liver to be used by other cells that can not utilize fatty acids as a fuel source

Triglycerides as Fuel Triglyceride metabolism Triglycerides are stored in adipocytes and used as fuel for cellular metabolism Lipolysis Breakdown of a triglyceride into glycerol and free fatty acids Occurs in adipose tissue Used to liberate stored energy during exercise and fasting Induced by: glucagon, NE, Epi, GH, ANP, cortisol

Typical Triglyceride Palmitic Acid Oleic Acid Alpha Linolenic Acid Glycerol + Fatty Acid Tails

Triglycerides as Fuel Fate of glycerol Glycerol is moved out of the adipocyte by aquaporins Glycerol is moved into hepatocytes by aquaporins In the liver: Glycerol is converted to DHAP then 3-PGAL Gluconeogenesis Glycogenesis In most cells: Glycolysis Glycerol enters glycolysis as PGAL Fate of fatty acids β-oxidation Produces Acetyl-CoA Many fates Dependent on the needs of the cell EXCEPTIONS 1. RBC s lack mitochondria 2. The brain Fatty acids have to be converted to ketones (in the liver) to be metabolized Long chain fatty acids can not cross the BBB

Fatty Acid Catabolism β-oxidation

Fatty Acid Catabolism β-oxidation Fatty acid catabolism consists of: 1. Fatty acids are moved into the cell Activation and membrane transport of free fatty acids into cells by binding to Co-A. 2. Fatty acid-co-a shuttled into the mitochondria 3. Oxidation of the β carbon to a carbonyl group (C=O). 4. Enzymes cleavage off 2-carbon segments resulting in acetyl-coa. 5. Needs of the cell determine what happens next

Triglyceride Structure Palmitin: A homotriglyceride made up of 3 palmitic acids (C 16 H 32 O 2 ) Found in chocolate!!

How Much ATP is Formed from Palmitin? 7 bonds 1 NADH + H + + 1 FADH 2 per bond CC CC CC CC CC CC CC CC 8 acetyl CoA each acetyl CoA -----> Krebs cycle 1 ATP X 8 = 8 ATP 3 NADH + H + X 8 = 24 NADH + H + 1 FADH 2 X 8 = 8 FADH 2

ATP From β Oxidation of 1 Fatty Acid ATP = NADH + H + 7 + 24 = 31 NADH + H + 31 X 3 = FADH 2 7 + 8 = 15 FADH 2 15 X 2 = 8 ATP 93 ATP 30 ATP 8 ATP 93 ATP +30 ATP Cost of initiating β-oxidation 131 ATP -1 ATP 130 ATP

How Much ATP for the Entire Triglyceride? Glycerol converted back to PGAL Yields 20 ATP Three 16-C fatty acid chains 3 x 130 ATP = 390 ATP Grand total 390 + 20 = 410 ATP

Ketones Acetoacetate and β-hydroxybutyrate Ketosis: The liver forms ketones from fatty acids for other tissues to use as fuel instead of glucose Not all tissues can metabolize fatty acids Ketogenic diet: High fat, low carbohydrate diet Fasting Extreme/Strenuous Exercise There are 2 ketones used by brain, heart, muscle and kidney 1. Acetoacetate (4C) 2. β-hydroxybutyrate (4C) In the brain Used to make long chain fatty acids that can not pass the BBB Diabetic Ketoacidosis (DKA) High levels of ketones causing plasma to become acidic

Ketones Acetone Acetone is a ketone that is not used as a fuel source Acetone (3 carbon) is produced as a waste product when acetoacetate is metabolized Diffuses to the lungs and is exhaled as a gas