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METABOLISM

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METABOLISM Lipolysis breakdown of lipids triglyceride 2 F.A.s + glycerol reaction is hydrolysis catalyzed by lipases epinephrine & norepinephrine stimulate breakdown ... – PowerPoint PPT presentation

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Title: METABOLISM


1
METABOLISM
2
Energy
  • needed for all physical metabolic activities
  • food principle source of energy
  • digested absorbed
  • supplies energy
  • serves as building blocks for synthesis of
    complex molecules
  • stored for future use

3
Metabolism
  • all chemical reactions occurring in an organism
  • involves
  • Catabolism
  • breakdown of organic molecules
  • releases energy
  • Anabolism
  • synthesis of new organic molecules
  • formation of new chemical bonds

4
Nutrients
  • metabolism requires nutrients
  • ingested chemicals needed for growth, repair or
    maintenance of body
  • obtained through ingestion digestion
  • absorbed from interstitial fluids
  • all organic building blocks available are placed
    into nutrient pool
  • can be turned into metabolic fuels
  • Macronutrients
  • must be consumed in large quantities
  • Carbohydrates
  • Lipids
  • Proteins
  • Micronutrients
  • only needed in small amounts
  • Vitamins
  • Minerals
  • Water
  • many can be manufactured by body
  • others cannot be made
  • essential nutrients

5
ATP
  • universal energy currency
  • adenosine tri-phosphate
  • PO4 bonds between phosphate groups-high energy
    bonds
  • PO4 groups are transferred from molecule to
    molecule ? provide energy to power cellular
    functions
  • ATP?ADP energy ? AMP energy

6
ATP
  • body has limited capacity to store ATP
  • maximum work levels? ATP depleted in seconds
  • to sustain activity need to continually replenish
    ATP
  • most cells make ATP by breaking down
    carbohydrates especially glucose
  • Glucose? oxidized? ATP energy

7
Carbohydrates
  • composed of monosaccharides
  • simple sugars
  • Glucose-C6H12O6
  • building block for complex carbohydrates
  • Disaccharides
  • formed by 2 monosaccharides
  • glucose fructose? sucrose
  • Polysaccharides
  • composed of repeating monosaccharides subunits
  • important in energy storage
  • Starch
  • carbohydrate store in plants
  • compact insoluble
  • Glycogen
  • polysaccharide energy storage form in animals
  • kind of animal starch

8
Carbohydrate Processing
  • digestion
  • complex carbohydrate converted to simpler,
    soluble form
  • can be transported across intestinal wall
    delivered to tissues
  • anabolic or biosynthetic reactions
  • small precursor molecules?macromolecules
    synthesized
  • lipids, proteins glycogen
  • catabolic reactions-oxidization
  • complete breakdown of glucose
  • C6H12O6 6O2 ?6CO2 6H2O ATP heat

9
Glucose Oxidation Steps
  • Glycolysis
  • occurs in cytosol
  • does not require oxygen
  • also called anaerobic
  • Formation of Acetyl COA
  • connects glycolysis with Krebs cycle
  • Krebs Cycle
  • occurs in mitochondria
  • require O2
  • aerobic
  • Electron Transport Chain
  • occurs in mitochondria
  • require O2
  • aerobic

10
Complete Oxidation of Glucose
  • C6H12O6 6O2 ?6CO2 6H2O
  • for one thing to be oxidized-another must be
    reduced
  • oxidation reduction reactions typically occur
    together
  • redox reactions

11
Oxidation/Reduction Reactions
  • Oxidation
  • occurs when H atoms are removed from compounds
  • Oxidized things lose electrons
  • electron lost?oxidized-loses energy
  • Reduction
  • occurs when H atoms are added to compounds
  • gain electron?reduced-gains energy
  • food fuels are oxidized-lose energy? transferred
    to other molecules?ATP
  • enzymes cannot accept H atoms
  • coenzymes act as hydrogen or electron acceptors
  • reduced each time substrate is oxidized

12
Hydrogen Atom Transfers
  • coenzymes found in glucose oxidation reactions
  • NAD-nicotinamide adenine dinucleotide
  • FAD-flavinadenine dinucleotide

13
Glycolysis
  • first step in complete oxidation of glucose
  • takes place in cytosol
  • begins when enzyme phosphorylates
  • adds PO4 group to glucose? Glu6PO4
  • traps glucose
  • most cells do not have enzyme to reverse reaction
    lack transport system for phosphorylated sugars
  • ensures glucose is trapped
  • Glu6PO4?isomerized?Fru6P? ATP ?
    fructose-1,6-bisphosphate-Fru 1,6diP
  • reactions use 2 ATPs
  • Energy investment phase

ATP
14
Glycolysis
  • glyceraldehyde-3-P dehydrogenase catalyzes NAD
    dependent oxidation of glyceraldehyde 3P?2
    pyruvates
  • H that is removed is picked up by NAD?NADH H
  • glucose 2NAD 2ADP pi?2 pyruvic acids
    2NADH 2 ATP

15
Glycolysis
16
Pyruvate
  • fate depends on oxygen availability
  • not enough oxygen
  • NAD is regenerated by converting pyruvate?lactic
    acid
  • anaerobic fermentation
  • limited by buildup of lactic acid
  • produces acid base problems
  • degrades athletic performances
  • impairs muscle cell contractions produces
    physical discomfort
  • O2 available
  • pyruvic acid enters aerobic pathways of Krebs
    cycle electron transport chain (ETC)
  • aerobic respiration

17
Aerobic Respiration
  • pyruvic acid enters mitochondria
  • aerobic pathways of Krebs cycle electron
    transport chain (ETC)
  • specific mechanisms transport pyruvate molecule
    into mitochondria
  • once inside? pyruvate dehydrogenase converts
    pyruvate?acetyl CoA
  • hydrogen atoms of pyruvate are removed by
    coenzymes
  • pyruvate is decarboxylated (carbons removed)
    released as CO2?diffuses out of cells into
    blood?expelled by lungs
  • pyruvic acid NAD coenzyme A? CO2 NADH
    Acetyl CoA

18
Acetyl CoA
  • major branch point in metabolism
  • 2 carbons can be converted into fatty acids,
    amino acids or energy

19
Krebs Cycle
  • named for discoverer, Hans Krebs
  • also tricarboxylic acid cycle or Citric Acid
    Cycle
  • during cycle hydrogen atoms are removed from
    organic molecules?transferred to coenzymes
  • begins ends with oxaloacetate (OAA)
  • acetyl CoA condenses with oxaloacetate- 4 carbon
    compound?citrate-6 carbon compound
  • cycle continues around through 8 successive step
  • during steps atoms of citric acid are rearranged
    producing different intermediates called keto
    acids
  • eventually turns into OAA

20
Krebs Cycle
  • complete revolution per acetyl CoA includes 2
    decarboxylations 4 oxidations
  • Yields
  • 2 CO2
  • reducing equivalents-3 NADH 1 FADH2
  • further oxidized in electron transport chain
  • 1 GTP-ATP equivalent
  • Since two pyruvates are obtained from oxidation
    of glucose? amounts need to be doubled for
    complete oxidation results

21
Electron Transport
  • transfers pairs of electrons from entering
    substrate to final electron acceptor-oxygen
  • reactions takes place on inner mitochondrial
    membrane
  • mitochondria have dual, inner membranes that are
    only permeable to water, oxygen CO2

22
Oxidative Phosphorylation/Electron Transport
Chain System
  • responsible for 90 of ATP used by cells
  • basis-2H O2?2 H20
  • releases great deal of energy all at once
  • cells cannot handle so much energy at one time
  • reactions occur in series of steps
  • Oxidation reactions
  • remove H atoms lose energy (H)
  • Oxidized things lose electrons
  • compounds that gain electrons? reduced-gain
    energy
  • enzymes cannot accept H atoms
  • Coenzymes needed to accept hydrogens
  • when coenzyme accepts hydrogen atoms? coenzyme
    reduced gains energy

23
Electron Transport Chain
  • during oxidative phosphorylation electrons are
    led through series of oxidation-reduction
    reactions before combining with O2 atoms

24
Chemiosmosis
  • ETC creates conditions needed for ATP production
    by creating steep concentration gradient across
    inner mitochondrial membrane
  • as energy is released as electrons are
    transferred ? drives H ion pumps that move H
    across membrane into space between 2 membranes
  • pumps create large concentration gradients for H
  • H ions cannot diffuse into matrix-not lipid
    soluble
  • channels allow H ions to enter matrix
  • Chemiosmosis
  • energy released during oxidation of fuelschemi
  • pumping H ions across membranes of mitochondria
    into inter membrane space osmo
  • creates steep diffusion gradient for Hs across
    membrane
  • when hydrogens flow across membrane, through
    membrane channel protein?ATP synthase attaches
    PO4 to ADP ?ATP

ATP synthase
25
Oxidative Phosphorylation
  • captures free energy released during electron
    transport couples it to phosphorylation of
    ADP?ATP
  • for each pair of electrons removed by NAD from
    substrate in TCA cycle?6 hydrogen ions are pumped
    across inner membrane of mitrochondria ?makes 3
    ATP
  • FAD?4 hydrogens pumped across?2 ATP

26
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27
Energy Yield
  • aerobic metabolism generates more ATP per mole of
    glucose oxidized than anaerobic metabolism
  • of 686 kcal of energy available in 1 mole of
    glucose?262 kcal are captured as ATP
  • 38 of energy
  • Glycolysis
  • net 2 ATPs
  • Krebs Cycle
  • 2 ATP
  • 8 NADH H X 324 ATP
  • 2 FADH2 X 24 ATP
  • 2 moles pyruvate?2 NADH H-glycolysis ?2 X 2
    4 ATP
  • Total 36 ATP

28
Carbohydrate Biosynthetic Reactions
  • anabolic reactions
  • small precursor molecules? macromoleculesynthesize
    d

29
Glycogenesis
  • consuming large quantity of glucose, does not
    form great deal of ATP
  • ATP cannot be stored
  • excess glucose stored as glycogen or fat
  • once glycolysis stops?glucose molecules
    combine?glycogen
  • animal carbohydrate storage product
  • glycogenesis
  • glucose enters cells? phosphorylated? glu-6-P?
    isomerized ? glu1PO4? glycogen synthase cleaves
    terminal PO4-attaches glucose to growing
    glycogen chain
  • reaction takes place mostly in liver skeletal
    muscle cells
  • blood glucose levels low glycogen breaks
    down?glycogenolysis

30
Gluconeogenesis
  • liver can only store enough glucose as glycogen
    to last about 12 hours
  • synthesis of new glucose from non carbohydrate
    sources- gluconeogenesis
  • carried out in liver
  • protects body especially nervous system from
    effects of hypoglycemia
  • glucose can be synthesized from amino acids,
    Krebs cycle intermediates, pyruvate or glycerol

31
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32
Lipids
  • most concentrated source of energy
  • highly efficient important energy store
  • capable of storing more energy for weight than
    carbohydrates
  • provide large amount of ATP
  • form compact fat droplets which exclude water
  • insoluble take up minimal space
  • most abundant dietary source-triglycerides
  • mainly stored in adipocytes
  • triglycerides contain 3 long chain fatty acids
    glycerol

33
Lipid Transport
  • lipids are not water soluble
  • most circulate as lipoproteins
  • lipid-protein complexes
  • spherical-protein, phospholipids cholesterol
    surrounding inner core of triglycerides
  • proteins in other shell are apoproteins
  • 4 groups by size proportion of lipid to protein
  • chylomicrons
  • 95 triglycerides
  • made by epithelial cells of small intestine
  • carry dietary lipids
  • enter lacteals?absorbed into lympth?blood stream
  • Travel to adipocytes where the fat is stored
  • VLDL -very low density lipoproteins
  • made by liver
  • carry endogenous lipids
  • transport to adipocytes for storage
  • LDL-low density lipoproteins
  • deliver cholesterol to tissues
  • carry 75 of bodys cholesterol

34
Lipolysis
  • breakdown of lipids
  • triglyceride?2 F.A.s glycerol
  • reaction is hydrolysis
  • catalyzed by lipases
  • epinephrine norepinephrine stimulate breakdown
  • insulin inhibits it
  • glycerol fatty acids are catabolized in
    different pathways

35
Glycerol Oxidation
  • converted to glyceraldehydes 3-PO4 (a product
    formed during glycolysis)
  • ATP-not needed- converted to glucose
  • ATP-needed-enters TCA cycle after being converted
    to pyruvic acid

36
Fatty Acid Oxidation-Beta Oxidation
  • fatty acids?mitochondria matrix
  • refers to oxidation at ?-carbon or 3rd position
  • removal occurs in repeating sequential removal of
    2-carbon units
  • attaches them to coenzyme A which enters Krebs
    cycle
  • for every 2 C fragments removed? 12 ATPs made
    from processing acetyl coA in Krebs cycle
  • fatty acids with odd number of carbons-broken to
    propionyl-CoA
  • 3 carbon compound
  • cannot enter another round of ?-oxidation
  • Propionyl-CoA? succinyl-CoA?Krebs cycle

37
Ketogenesis
  • process by which excess acetyl groups can be
    metabolized by liver
  • 2acetyl groups condense? acetoacetic acid
  • some is converted to beta hydroxybutyric acid
    acetone
  • ketone bodies
  • able to cross plasma membranes
  • enter the blood stream
  • some cells use these by attaching them to 2
    coenzyme A molecules?2 acetyl coA molecules which
    can enter Krebs cycle

38
Lipogenesis
  • glucose amino acid levels high?stored in
    adipose tissue
  • Lipogenesis
  • body cannot make all fatty acids
  • ones that cannot be made are essential fatty
    acids
  • linoleic acid or linolenic
  • must be obtained in diet

39
Lipid Metabolism
40
Proteins
  • polymers of amino acids joined by peptide
    bonds?peptide? protein
  • basic building blocks of cells
  • comprise
  • cell structure
  • skin
  • keratin-hair, nails
  • connective tissue-tendons, cartilage, muscles
  • membranes
  • serve as enzymes
  • facilitate chemical reactions
  • part of hemoglobin
  • hormones

41
Amino Acids
  • 20 amino acids
  • 10 essential
  • cannot be made by body
  • body cant make 8
  • isoleucine, leucine, lysine, phenylalaine,
    valine, methionine, tryptophane threonine
  • do not make inadequate amounts of arginine
    histidine

42
Proteins
  • ingested in animal products
  • complete proteins
  • Ingested via other sources
  • incomplete proteins
  • low in one or more essential amino acids
  • excess proteins are not stored
  • liver continually breaks proteins down absorbs
    amino acids from blood
  • amino acids can be used to make new proteins or
    in TCA cycle?ATP
  • not enough carbohydrates or fats ingested to make
    ATP?dietary tissue proteins can be broken down
    to provide energy
  • average ATP yield-similar to yield from
    carbohydrates
  • impractical energy sources
  • more difficult to break down than carbohydrates
    or lipids
  • breakdown produces ammonia as byproduct
  • toxic
  • needed for structural functional uses in cells
  • loss of too much would endanger homeostasis

43
Protein Metabolism
  • digestion breaks down into amino acids
  • before can be oxidized or catabolized?must be
    deaminated
  • occurs in liver
  • involves removal of amino group H
    atom?NH3-ammonia or NH4
  • Ammonia is toxic
  • body cannot allow high concentrations to
    accumulate
  • removed by converting it to urea in urea cycle
  • once amino acids are ready-can be converted into
    glucose (gluconeogenesis), into fatty acids
    (lipogenesis) or into ketone bodies (ketogenesis)

44
Protein Metabolism
  • new proteins can be made by forming peptide bonds
    between amino acids
  • carried out on ribosomes
  • directed by DNA and RNA
  • non-essential amino acids can be made by
    transamination
  • transfer of amino group from amino acid to
    pyruvate or to an acid (ketoacid) in Krebs cycle
  • original amino acid becomes keto
    acid-intermediate in Krebs Cycle
  • can be broken down in that cycle
  • most amino acids transfer amine group to
    ?-ketoglutarate
  • amino acid ketoacid?ketoacid amino
    acid-glutamic acid

45
Absorptive Post Absorptive States
  • over 24 hours body two patterns of metabolic
    activity
  • Absorptive
  • fed state
  • Post absorptive
  • fasting stage
  • metabolic controls equalize blood concentration
    of nutrients between these 2 states

46
Absorptive State
  • time during shortly after eating
  • lasts about 4 hrs
  • energy sources are absorbed stored
  • overall biosynthesis of stored reserves such as
    glycogen, protein fat
  • Anabolic processesgt catabolic processes

47
Absorptive State
  • primary hormone-insulin
  • directs nearly all events of absorptive state
  • Hypoglycemic
  • takes glucose out of blood
  • glucose increasesgt100mg glucose/100ml blood?
    humoral stimulus?? cells pancreatic
    islets?insulin
  • release enhanced by GI tract hormones especially
    gastrin, CCK secretin by elevated amino acid
    levels
  • binds to membrane receptors on target
    cells?activates carrier mediated facilitated
    diffusion of glucose into cells?increases glucose
    into cells 15-20X within seconds

48
Absorptive Processes
  • lipids, proteins carbohydrates are ingested
    absorbed by intestinal mucosa
  • 50 of glucose is oxidized to ATP
  • Glucose?glycogen (glycogenesis)
  • fatty acids?packaged in chylomircons ?enter
    lacteals?stored as fat
  • excess glucose transported to adipocytes
    stored as triglycerides
  • amino acids enter hepatocytes where they are
    deaminated to ketoacids either enter the Krebs
    cycle?ATP or used in fatty acid synthesis

49
Post Absorptive State
  • GI tract empty
  • no nutrient absorption
  • body relieves on internal energy resources
    supplied by breakdown of body reserves
  • occurs during late morning, afternoon all night
  • about 12 hours
  • metabolic activity focuses on mobilization of
    energy reserves maintenance of normal glucose
    levels
  • coordinated by hormones neural mechanisms

50
Post Absorptive State
  • glucose below 80 mg/dl? glycogen reserves broken
    down-glycogenolysis
  • epinephrine, growth hormone glucocoricoids ?fat
    mobilization-adipocytes? lipolysis ?fatty acids
    glycerol?glucose
  • as glucose reserves continue to
    decrease?gluconeogenesis using amino acids
    lactic acid begins
  • fat undergoes beta oxidation ?acetyl CoA?TCA
    cycle? ATP? used in gluconeogenesis or converted
    to ketone bodies which can be used by peripheral
    tissues for energy

51
Post Absorptive State Regulation
  • hormones sympathetic division of ANS
  • blood glucose levels decrease?pancreatic alpha
    cells?glucagon ? liver (primary target? increases
    glucose in blood from gluconeogenesis
    glucogenolysis

52
Post Absorptive State Regulation
  • low blood glucose? stimulates sympathetic nervous
    system?increases output? epinephrine
    (neurotransmitter)?glycogen breakdown
  • sympathetic nervous system?increases
    output?adrenal medulla?epinephrine
    norepinephrine?lipolysis

53
Metabolism Overview
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