Badil Dass. Karachi King s College of Nursing

Transcription

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2 Badil Dass Lecturer Karachi King s College of Nursing

3 Metabolism Badil Dass Lecturer

4 By the end of this presentation, you will be able to: Define metabolism, catabolism and anabolism. Define ATP and its relationship with catabolism and anabolism. Discuss gluconeogenesis,glycogenesis, glucogenolysis,transamination, deamination and ketosis. Discuss the following metabolic pathways for carbohydrate, proteins and fats in terms of glycolysis, kreb s cycle and electron transport chain.

5 Metabolism The sum total of the chemical processes that occur in living organisms, resulting in growth, production of energy, elimination of waste material, etc. Anabolism- build up of complex molecules Catabolism- break down of complex molecules

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7 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.

8 Oxidation is the removal of electron from an atom or molecule, the result is decreases in potential energy of atom or molecule. Most of biological oxidation reactions involve the loss of hydrogen atoms, they are called dehydrogenation reaction. Example conversion of lactic acid into pyruvic acid.

9 Reduction is the opposite of oxidation,it is the addition of electrons to a molecule. Example: conversion of pyruvic acid into lactic acid. Oxidation and reduction reactions are always coupled ;each time one substance and another is simultaneously reduced.such paired reactions are called oxidationreduction or redox reactions.

10 Substrate-level phosphorylation Substrate transfers a phosphate group directly Requires enzymes Phosphocreatine + ADP Creatine + ATP Oxidative phosphorylation Method by which most ATP formed Small carbon chains transfer hydrogens to transporter (NAD or FADH) which enters the electron transport chain

11 Primarily glucose Fructose and galactose enter the pathways at various points All cells can utilize glucose for energy production Glucose uptake from blood to cells usually mediated by insulin and transporters Liver is central site for carbohydrate metabolism Glucose uptake independent of insulin The only exporter of glucose

12 Several cell types prefer glucose as energy source mg/dl is normal range of blood glucose in non-ruminant animals Uses of glucose: Energy source for cells Muscle glycogen Fat synthesis if in excess of needs

13 Storage as glycogen Liver Skeletal muscle Storage as lipids Adipose tissue Metabolized for energy New glucose synthesized Fed state Fasted state

14 High Blood Glucose Pancreas Muscle Glucose absorbed Insulin Adipose Cells Glycogen Glucose absorbed Glucose absorbed

15 Four major metabolic pathways: Immediate source of energy Pentophosphate pathway Glycogen synthesis in liver/muscle Precursor for triacylglycerol synthesis Energy status (ATP) of body regulates which pathway gets energy Same in ruminants and non-ruminants

16 1 st Priority: glycogen storage Stored in muscle and liver 2 nd Priority: provide energy Oxidized to ATP Only excess glucose 3 rd Priority: stored as fat Stored as triglycerides in adipose The body can store about 500 g(1.1 lb)of glycogen.

17 Glucose storage: Glycogenesis If glucose is not needed immediately for ATP production, it combines with many other molecules of glucose to form glycogen, a polysaccrides that is the only stored form the CHO in our bodies. The harmone insuline stimulates the hepatocytes and skeletal muscle cells to carry out glycogenesis, the synthesis of glycogen. The body can store about 500g(about 1.1 lb) of glycogen, roughly 75% in skeletal muscle fibres and the rest in liver cells.

18 Contd. During the glycogenesis, glucose is first phosphorylated to glucose 6-phosphate by hexokinase. Glucose 6-phosphate is converted to glucose 1- Glucose 6-phosphate is converted to glucose 1- phosphate, then to uridine diphosphate glucose and finally to glycogen.

19 Glucose release: Glucogenolysis When body activities require ATP, glycogen stored in hepatocytes is broken down into glucose and released into the blood to be transported to cells, where it will be catabolized by the processes of cellular respiration. The process of splitting glycogen to glucose subunits is called glycogenolysis.

20 Protein Metabolism

21 During digestion, proteins are broken down into amino acids. Unlike CHO and TGL, which are stored. Proteins are not warehoused for future use. 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).

22 The fate of proteins The active transport of amino acids into body cells is stimulated by insulinlike growth factors(igfs) and insulin. Almost immediately after digestion, amino acids are reassembled into proteins. Many proteins function as enzymes; others are involved in transportation(hemoglobin) or serve as antibodies, clotting chemicals(fibrinogen), harmones (insulin) or contractile elementsin muscle fibers(actin or myosin).

23 No storage facility for amino acids Amino acids incorporated into functional proteins Amino acids in blood and extracellular fluid represent an amino acid pool Amino acids move through this pool Average 60 kg woman 10 kg protein 170 g free amino acids in pool

24 Protein content of adult body remains remarkably constant. Protein constitutes 10-15% 15% of diet. Equivalent amount of amino acids must be lost each day. Proteins synthesis in all body cells and is stimulated by insulin,thyroid harmones and insulinlike growth factors

25 Metabolism of amino acids differs, but 3 common reactions: Transamination Deamination Formation of urea

26 Amino group removed from one amino acid and transferred to another Catalysed by aminotransferase enzymes Nearly all transaminations transfer amino group to α- ketoglutarate Forms new ketoacid and glutamate (amino acid)

27 Amino group (and H) removed Forms ammonia (NH 3 ) Carbon skeleton left can be Oxidised used for gluconeogenesis converted to fatty acid 18 amino acids glucogenic/ketogenic Leucine and lysine purely ketogenic

28 Ammonia is toxic Readily ionises to ammonium ion NH + 4 NH + 4 converted to urea in liver (urea cycle) Urea contains 2 x NH 2 One from NH + 4 One from aspartate Urea excreted in urine

29 Lipid Metabolism

30 Fats are not water soluble Made into bile salts that are Absorbed as micelles in small intestines. The lipid and protein combination is lipoproteins There are four major classes of lipoproteins: Chylomicrons Very low density lipoproteins(vldls) Low density lipoproteinsi(ldl) High density lipoproteins(hdl)

31 Chylomicron Carriers Proteins that carry fats Proteins that carry fats stored in adipose tissue It forms in mucosal epithelial cells of the small intestine, transport dietry (ingested) lipids to adipose tissue for storage. They contain about 1-2% proteins,85%tgl,7% phospholipids and 6-7% cholesterol.

32 Which form in hepatocytes, contain mainly endogenous lipids (made in the body). VLDLs contain about 10% proteins, 50% TGL, 20 % phospholipids and 20% cholesterol.

33 Contains 25% proteins, 5% TGL, 20% phospholipids and 50% cholesterol. They carry about 75% of the total cholesterol in blood and deliver it to cells throughout the body for use in repair of cell membranes and synthesis of steroid harmones and bile salts.

34 Which contain 40-45% proteins,5-10% triglycerides,30% phospholipids,and 20% cholesterol, remove excess cholesterol from body cells and the blood and transport it to the liver for elimination.because HDLs prevent accumulation of cholesterol in the blood,a high HDL level is associated with decreased risk of coronary artery disease.for this reason,hdlcholesterol is known as good cholesterol

35 In order for muscle, liver and adipose tissue to oxidize the fatty acids derived from triglycerides to produce ATP, the triglycerides must first be split into glycerol and fatty acids, a process called lipolysis. Lipolysis is catalyzed by enzyme called lipases. Epinephrine and norepinephrine enhance TGL breakdown into fatty acids and glycerol.

36 As a part of normal fatty acid catabolism, hepatocytes can take two acetyl molecules at a time and condense them to form acetoacetic acid. This reaction liberates the bulky CoA portion, which cannot diffuse out of cells some acetoacetic acid is converted into betahydroxybutyric acid and acetone. The formation of these three substances collectively known as ketone bodies, is called ketogenesis.

37 Liver cells and adipose cells can synthesize lipids from glucose or amino acids through lipogenesis, which is stimulated by insulin. Lipogenesis occurs when individuals consume more calories than are needed to satisfy their ATP needs.

38 The chemical reactions of living systems depend on the effecient transfer of manageable amounts of energy from one molecule to another. The molecule that most often performs this task is ATP. A typical cell cell has about a billion molecules of ATP. Molecule of ATP consists of an adenine molecule,a ribose molecule,and three phosphate groups bonded to one another.

39 Cont. when the terminal phosphate group is split off ATP,adenosine diphosphate [ADP] and a phosphate group[symbolized as (P) are formed. some of the energy released is used to drive anabolic some of the energy released is used to drive anabolic reactions such as the formation of glycogen from glucose.

40 Energy Transfer Oxidation is the removal of electrons from a substance. Reduction is the addition of electrons to substance. Two coenzymes that carry hydrogen atoms during coupled oxidation-reductions are nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (NAD). ATP can generated via substrate-level phosphorylation, oxidative phosphorylation and photophosphorylation.

41 kreb s cycle The Krebs cycle named after the person who discovered it in 1937, Hans Krebs is known by several other names including: The citric acid cycle Tricarboxylaic acid cycle(tca)

42 Contd. The purpose of Krebs cycle is to link the aerobic and anaerobic phases of metabolism in order to maximize 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.

43 Contd. In order to apply these concepts to the Krebs cycle, one must understand redox reactions and the process of ATP resynthesis.

44 Understanding of redox reactions Within a cell oxidation and reduction reactions are always coupled. In other words, when one substance oxidized another is simultaneously reduced. Such coupled reactions are referred to as redox reactions.

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46 The eight reactions of the Krebs cycle 1)Entry of the acetyl group.the chemical bond that attaches the acetyl group to coenzyme a(coa)breaks,and the two-carbon acetyl group attaches to a four carbon molecule of oxaloacetic acid to form a six-carbonmolecule called citric acid. CoA is free to combine with another acetyl group from pyruvic acid and repeat the process.

47 2)Isomerization.citric acid undergoes isomerization to isocitric acid, which has the same molecular formula as citrate.notice,however, that the hydroxel group (_oh)is attached to a different carbon.

48 3)Oxidative decarboxylation.isocitric acid is oxidized and loses a molecule of co2, forming alphaketoglutaric acid.the h- from the oxidation is passed on to nad+,which is reduced to Nadh+h+.

49 4)Oxidative decarboxylation.alpha-ketoglutaric acid is oxidized,loses a molecule of co2,and picks up coa to form succinyl coa.

50 5)Substrate-level phosphorylation.coa is displaced by a phosphate group,which is then transferred to guanosine diphosphate (gdp) to form guanosine triphosphate (gtp).gtp can donate a phosphate group to adp to form ATP.

51 6)Dehydrogenation.succinic acid is oxidized to fumaric acid as two of its hydrogen atoms are transferred to the coenzyme flavin adenine dinucleutide (fad),which is reduced to fadh2.

52 7)Hydration.fumaric acid is converted to malic acid by the addition of a molecule of water.

53 8)Dehydrogenation.in the final step in the 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.

54 References Tortora 2006.Principles of Anatomy and Physiology. Rose and Wilson,Anatimy and Physiology.

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