METABOLISM

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METABOLISM
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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Hydrogen Atom Transfers

• coenzymes found in glucose oxidation reactions
• NAD-nicotinamide adenine dinucleotide
• FAD-flavinadenine dinucleotide

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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
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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

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Glycolysis
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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

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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

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Acetyl CoA

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

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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

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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

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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

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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

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Electron Transport Chain

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

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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
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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

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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

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Carbohydrate Biosynthetic Reactions

• anabolic reactions
• small precursor molecules? macromoleculesynthesize
  d

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Lipid Metabolism
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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

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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

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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

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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)

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Metabolism Overview