Generic metabolism [compatibility mode]


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Generic metabolism [compatibility mode]

  1. 1. 7/6/2012 Metabolism By Shahzad Bashir RN, BScN (NMC ION) Objectives Metabolism By the end of this presentation, you will be able to: Define metabolism, catabolism and anabolism. The sum total of the chemical processes that Define ATP and its relationship with catabolism occur in living organisms, resulting in growth, and anabolism. production of energy, elimination of waste material, etc. Discuss gluconeogenesis,glycogenesis,glucogenolysis,transamination, deamination and ketosis. Anabolism- build up of complex molecules Discuss the following metabolic pathways for Catabolism- break down of complex carbohydrate, proteins and fats in terms of molecules glycolysis, kreb’s cycle and electron transport chain. Adenosine triphosphate • An important carrier of energy in cells in the body and a compound that is important in the synthesis (the making) of RNA. Adenosine triphosphate (ATP) is a nucleotide (a building block of a nucleic acid such as RNA). The body produces ATP from food and then ATP produces energy as needed by the body. • 1
  2. 2. 7/6/2012 Oxidation-Reduction Reactions Reduction Oxidation is the removal of electron from an atom or molecule, the result is decreases in Reduction is the opposite of oxidation,it is the potential energy of atom or molecule. addition of electrons to a molecule. Most of biological oxidation reactions involve Example: conversion of pyruvic acid into lactic the loss of hydrogen atoms, they are called acid. dehydrogenation reaction. Oxidation and reduction reactions are always Example conversion of lactic acid into pyruvic coupled ;each time one substance and another is acid. simultaneously reduced.such paired reactions are called oxidation-reduction or redox reactions. Mechanisms of ATP Formation Carbohydrate Metabolism Substrate-level phosphorylation Primarily glucose Substrate transfers a phosphate group directly Fructose and galactose enter the pathways at various Requires enzymes points Phosphocreatine + ADP Creatine + ATP All cells can utilize glucose for energy production Oxidative phosphorylation Glucose uptake from blood to cells usually mediated by insulin and transporters Method by which most ATP formed Liver is central site for carbohydrate metabolism Small carbon chains transfer hydrogens to transporter (NAD or FADH) which enters the Glucose uptake independent of insulin electron transport chain The only exporter of glucose Blood Glucose Homeostasis Fates of Glucose Several cell types prefer glucose as energy Fed state source Storage as glycogen 80-100 mg/dl is normal range of blood glucose in Livernon-ruminant animals Skeletal muscle Uses of glucose: Storage as lipids Energy source for cells Adipose tissue Muscle glycogen Fasted state Fat synthesis if in excess of Metabolized for energy needs New glucose synthesized 2
  3. 3. 7/6/2012 High Blood Glucose Glucose Metabolism Pancreas Four major metabolic pathways: Muscle Insulin Glycogen Immediate source of energy Pentophosphate pathwayGlucose absorbed Glucose absorbed Glycogen synthesis in liver/muscle Adipose Precursor for triacylglycerol synthesis Cells Energy status (ATP) of body regulates which Glucose absorbed pathway gets energy Same in ruminants and non-ruminants Fate of Absorbed Glucose Glucose storage: Glycogenesis If glucose is not needed immediately for ATP 1st Priority: glycogen storage production, it combines with many other molecules Stored in muscle and liver of glucose to form glycogen, a polysaccrides that is the only stored form the CHO in our bodies. 2nd Priority: provide energy The harmone insuline stimulates the hepatocytes Oxidized to ATP and skeletal muscle cells to carry out glycogenesis, 3rd Priority: stored as fat the synthesis of glycogen. Only excess glucose The body can store about 500g(about 1.1 lb) of glycogen, roughly 75% in skeletal muscle fibres and Stored as triglycerides in adipose the rest in liver cells. The body can store about 500 g(1.1 lb)of glycogen. Contd. Glucose release: Glycogenolysis During the glycogenesis, glucose is first When body activities require ATP, glycogen phosphorylated to glucose 6- phosphate by stored in hepatocytes is broken down into hexokinase. glucose and released into the blood to be Glucose 6-phosphate is converted to glucose transported to cells, where it will be 1-phosphate, then to uridine diphosphate catabolized by the processes of cellular glucose and finally to glycogen. respiration. The process of splitting glycogen to glucose subunits is called glycogenolysis. 3
  4. 4. 7/6/2012 During digestion, proteins are broken down into amino acids. Unlike CHO and TGL, which are stored. Proteins are not warehoused for future use. Protein Metabolism Instead, amino acids are either oxidized to produce ATP or used to synthesized new proteins for body repair and growth. Excess dietary amino acids are not excreted in the urine and feces but instead are converted into glucose (gluconeogenesis) or TGL (lipogenesis). The fate of proteins Amino acid pool The active transport of amino acids into body cells is stimulated by insulinlike growth factors(IGFs) and No storage facility for amino acids insulin. Amino acids incorporated into functional proteins Almost immediately after digestion, amino acids are Amino acids in blood and extracellular fluid represent reassembled into proteins. an ‘amino acid pool’ Many proteins function as enzymes; others are involved in transportation(hemoglobin) or serve as Amino acids move through this pool antibodies, clotting chemicals(fibrinogen), harmones Average 60 kg woman (insulin) or contractile elementsin muscle fibers(actin 10 kg protein 170 g free amino acids in pool or myosin). Fate of amino acids Amino acid metabolism Protein content of adult body remains Metabolism of amino acids differs, but 3 common remarkably constant. Protein constitutes 10-15% of diet. 10- reactions:Equivalent amount of amino acids must be lost each day. Transamination Proteins synthesis in all body cells and is Deamination stimulated by insulin,thyroid harmones and insulinlike growth factors Formation of urea 4
  5. 5. 7/6/2012 Transamination reactions Deamination reactionsAmino group removed from one amino acid and Amino group (and H) removed transferred to another Forms ammonia (NH3) Catalysed by aminotransferase enzymes Carbon skeleton left can be Nearly all transaminations transfer amino group to α- Oxidised ketoglutarate used for gluconeogenesis Forms new ketoacid and glutamate (amino acid) converted to fatty acid 18 amino acids glucogenic/ketogenic Leucine and lysine purely ketogenic Urea cycle Ammonia is toxic Readily ionises to ammonium ion NH4+ Lipid Metabolism NH4+ converted to urea in liver (urea cycle) Urea contains 2 x NH2 One from NH4+ One from aspartate Urea excreted in urine Lipid Metabolism Fats are not water soluble Chylomicron Carriers Made into bile salts that are Absorbed as micelles in small intestines. Proteins that carry fatsThe lipid and protein combination is lipoproteins stored in adipose tissue There are four major classes of lipoproteins: It forms in mucosal epithelial cells of the small intestine, transport dietry (ingested) Chylomicrons lipids to adipose tissue for storage. Very low density lipoproteins(VLDLs) They contain about 1-2% proteins,85%TGL,7% Low density lipoproteinsI(LDL) phospholipids and 6-7% cholesterol. High density lipoproteins(HDL) 5
  6. 6. 7/6/2012 Very low density Low density lipoproteinsI(LDL) lipoproteins(VLDLs) Contains 25% proteins, 5% TGL, 20% Which form in hepatocytes, contain mainly phospholipids and 50% cholesterol. endogenous lipids (made in the body). They carry about 75% of the total cholesterol in VLDLs contain about 10% proteins, 50% TGL, 20 blood and deliver it to cells throughout the body for % phospholipids and 20% cholesterol. use in repair of cell membranes and synthesis of steroid harmones and bile salts. High density lipoproteins(HDL) Lipid catabolism: Lipolysis Which contain 40-45% proteins,5-10% In order for muscle, liver and adipose tissue to triglycerides ,30% phospholipids ,and 20% oxidize the fatty acids derived from triglycerides to cholesterol, remove excess cholesterol from body produce ATP, the triglycerides must first be split intocells and the blood and transport it to the liver for glycerol and fatty acids, a process called lipolysis.elimination.Because HDLs prevent accumulation of Lipolysis is catalyzed by enzyme called lipases. cholesterol in the blood,a high HDL level is Epinephrine and norepinephrine enhance TGL associated with decreased risk of coronary artery breakdown into fatty acids and glycerol.disease.for this reason,HDL-cholesterol is known as “good cholesterol” As a part of normal fatty acid catabolism, Lipid Anabolism: Lipogenesis hepatocytes can take two acetyl molecules at atime and condense them to form acetoacetic acid. Liver cells and adipose cells can synthesize lipids from glucose or amino acids through lipogenesis, This reaction liberates the bulky CoA portion, which is stimulated by insulin. which cannot diffuse out of cells some acetoacetic acid is converted into beta- Lipogenesis occurs when individuals consume hydroxybutyric acid and acetone. more calories than are needed to satisfy their ATP The formation of these three substances needs. collectively known as ketone bodies, is called ketogenesis. 6
  7. 7. 7/6/2012 COUPLING OF CATABOLISM AND ANABOLISM BY ATP Cont. The chemical reactions of living systems depend when the terminal phosphate group is split offon the effecient transfer of manageable amounts ATP,adenosine diphosphate [ADP] and a of energy from one molecule to another. phosphate group[symbolized as (P) are The molecule that most often performs this task formed . is ATP. some of the energy released is used to drive A typical cell cell has about a billion molecules of anabolic reactions such as the formation of ATP. glycogen from glucose. Molecule of ATP consists of an adenine molecule ,a ribose molecule,and three phosphate groups bonded to one another. Energy Transfer kreb’s cycle Oxidation is the removal of electrons from a The Krebs cycle named after the person who substance. discovered it in 1937, Hans Krebs is known by Reduction is the addition of electrons to substance. several other names including: Two coenzymes that carry hydrogen atoms during coupled oxidation-reductions are nicotinamide The citric acid cycle adenine dinucleotide (NAD) and flavin adenine Tricarboxylaic acid cycle(TCA) dinucleotide (NAD). ATP can generated via substrate-level phosphorylation, oxidative phosphorylation and photophosphorylation. Contd. Contd. The purpose of Krebs cycle is to link the In order to apply these concepts to the Krebs aerobic and anaerobic phases of metabolism cycle, one must understand redox reactions in order to maximize ATP resynthesis. and the process of ATP resynthesis. This is accomplished through the oxidation of high energy organic compounds in the mitochondrial matrix. Since free electrons are unable to exist, the electrons released in an oxidation must be transferred to a carrier molecule. 7
  8. 8. 7/6/2012Understanding of redox reactionsWithin a cell oxidation and reductionreactions are always coupled.In other words, when one substance oxidizedanother is simultaneously reduced.Such coupled reactions are referred to asredox reactions.The eight reactions of the Krebs cycle1)Entry of the acetyl group.the chemical bond 2)Isomerization.citric acid undergoesthat attaches the acetyl group to coenzyme isomerization to isocitric acid, which has thea(coA)breaks,and the two- carbon acetyl same molecular formula asgroup attaches to a four –carbon molecule of citrate.notice,however, that the hydroxeloxaloacetic acid to form a six-carbonmolecule group (_oh)is attached to a different carbon.called citric acid.CoA is free to combine with another acetylgroup from pyruvic acid and repeat theprocess.3)Oxidative decarboxylation.isocitric acid is 4)Oxidative decarboxylation.alpha-oxidized and loses a molecule of co2, forming ketoglutaric acid is oxidized ,loses a moleculealpha-ketoglutaric acid.the h- from the of co2,and picks up coA to form succinyl coa.oxidation is passed on to nad+,which isreduced to Nadh+h+. 8
  9. 9. 7/6/2012 5)Substrate-level phosphorylation.coa is 6)Dehydrogenation.succinic acid is oxidized to displaced by a phosphate group,which is then fumaric acid as two of its hydrogen atoms are transferred to guanosine diphosphate (gdp) to transferred to the coenzyme flavin adenine form guanosine triphosphate (gtp).gtp can dinucleutide (fad),which is reduced to fadh2. donate a phosphate group to adp to form ATP. 7)Hydration.fumaric acid is converted to malic 8) the final step in the acid by the addition of a molecule of water. cycle,malic acid is oxidized to re-form oxaloacetic acid.two hydrogen atoms are removed are removed and one is transferred to nad+,which is reduced to nadh+h+.the regenerated oxaloacetic acid can combine with another molecule of acetyl coa,beginning a new cycle. References• Tortora 2006.Principles of Anatomy and Physiology.• Rose and Wilson,Anatimy and Physiology. 9