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METABOLISM
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
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
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
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
• ATPADP + energy AMP + energy
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
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
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
moleculesmacromolecules synthesized
– lipids, proteins & glycogen• catabolic reactions-oxidization
– complete breakdown of glucose• C6H12O6 + 6O2 6CO2 + 6H2O + ATP
+ heat
Glucose Oxidation Steps• Glycolysis
– occurs in cytosol– does not require oxygen– also called anaerobic
• Formation of Acetyl COA– connects glycolysis with
Kreb’s cycle
• Kreb’s Cycle– occurs in mitochondria– require O2
– aerobic
• Electron Transport Chain– occurs in mitochondria– require O2
– aerobic
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
Oxidation/Reduction Reactions• Oxidation
– occurs when H+ atoms are removed from compounds
• Oxidized things lose electrons• electron lostoxidized-loses
energy• Reduction
– occurs when H+ atoms are added to compounds
• gain electronreduced-gains energy
• food fuels are oxidized-lose energy transferred to other moleculesATP
• enzymes cannot accept H atoms• coenzymes act as hydrogen or
electron acceptors– reduced each time substrate
is oxidized
Hydrogen Atom Transfers• coenzymes found in glucose oxidation
reactions• NAD+-nicotinamide adenine dinucleotide• FAD-flavinadenine dinucleotide
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• Glu6PO4isomerizedFru6P+
ATP fructose-1,6-bisphosphate-Fru 1,6diP
• reactions use 2 ATPs• Energy investment phase
ATP
Glycolysis• glyceraldehyde-3-P
dehydrogenase catalyzes NAD+ dependent oxidation of glyceraldehyde 3P2 pyruvates
• H+ that is removed is picked up by NAD+NADH + H+
• glucose + 2NAD + 2ADP + pi2 pyruvic acids + 2NADH + 2 ATP
Glycolysis
Pyruvate• fate depends on oxygen availability• not enough oxygen
– NAD+ is regenerated by converting pyruvatelactic 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
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 pyruvateacetyl CoA
• hydrogen atoms of pyruvate are removed by coenzymes
• pyruvate is decarboxylated (carbons removed) released as CO2diffuses out of cells into bloodexpelled by lungs
• pyruvic acid + NAD + + coenzyme A CO2 + NADH + Acetyl CoA
Acetyl CoA• major branch point
in metabolism
• 2 carbons can be converted into fatty acids, amino acids or energy
Krebs Cycle• named for discoverer, Hans Krebs
– also tricarboxylic acid cycle or Citric Acid Cycle
• during cycle hydrogen atoms are removed from organic moleculestransferred to coenzymes
• begins & ends with oxaloacetate (OAA)
• acetyl CoA condenses with oxaloacetate- 4 carbon compoundcitrate-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
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
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
Oxidative Phosphorylation/Electron Transport Chain System
• responsible for 90% of ATP used by cells
• basis-2H + O22 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
Electron Transport Chain• during oxidative phosphorylation electrons are led
through series of oxidation-reduction reactions before combining with O2 atoms
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 fuels=chemi
– 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 proteinATP synthase attaches PO4 to ADP ATP
ATP synthase
Oxidative Phosphorylation• captures free energy
released during electron transport & couples it to phosphorylation of ADPATP
• for each pair of electrons removed by NAD from substrate in TCA cycle6 hydrogen ions are pumped across inner membrane of mitrochondria makes 3 ATP
• FAD4 hydrogens pumped across2 ATP
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 glucose262 kcal are captured as ATP
• 38% of energy • Glycolysis
– net 2 ATPs
• Krebs Cycle– 2 ATP– 8 NADH + H+ X 3=24 ATP– 2 FADH2 X 2=4 ATP
• 2 moles pyruvate2 NADH + H+-glycolysis 2 X 2 = 4 ATP
• Total 36 ATP
Carbohydrate Biosynthetic Reactions
• anabolic reactions
–small precursor molecules macromoleculesynthesized
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 stopsglucose
molecules combineglycogen– 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 downglycogenolysis
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
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
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 lactealsabsorbed into lympthblood 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 body’s cholesterol• excess-desposited around arteries• HDL-high density lipoproteins- good cholesterol• contain equal amounts of lipid & protein• transport excess cholesterol to liver for storage
Lipolysis• breakdown of lipids• triglyceride2 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
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
Fatty Acid Oxidation-Beta Oxidation• fatty acidsmitochondria 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-CoAKrebs cycle
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 molecules2 acetyl coA molecules which can enter Kreb’s cycle
Lipogenesis• glucose & amino acid
levels highstored 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
Lipid Metabolism
Proteins• polymers of amino acids joined
by peptide bondspeptide 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
Amino Acids• 20 amino acids• 10 essential
– cannot be made by body
• body can’t make 8• isoleucine, leucine,
lysine, phenylalaine, valine, methionine, tryptophane & threonine
• do not make inadequate amounts of arginine & histidine
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 cycleATP• not enough carbohydrates or fats ingested to
make ATPdietary & 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
Protein Metabolism• digestion breaks down into amino
acids• before can be oxidized or
catabolizedmust be deaminated– occurs in liver
• involves removal of amino group & H atomNH3-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)
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 + ketoacidketoacid +
amino acid-glutamic acid
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
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 processes> catabolic
processes
Absorptive State• primary hormone-insulin• directs nearly all events of
absorptive state• Hypoglycemic
– takes glucose out of blood• glucose increases>100mg
glucose/100ml blood humoral stimulus cells pancreatic isletsinsulin
• release enhanced by GI tract hormones especially gastrin, CCK & secretin & by elevated amino acid levels
• binds to membrane receptors on target cellsactivates carrier mediated facilitated diffusion of glucose into cellsincreases glucose into cells 15-20X within seconds
Absorptive Processes• lipids, proteins & carbohydrates
are ingested & absorbed by intestinal mucosa
• 50% of glucose is oxidized to ATP
• Glucoseglycogen (glycogenesis)
• fatty acidspackaged in chylomircons enter lactealsstored as fat
• excess glucose transported to adipocytes & stored as triglycerides
• amino acids enter hepatocytes where they are deaminated to ketoacids & either enter the Krebs cycleATP or used in fatty acid synthesis
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
Post Absorptive State• glucose below 80 mg/dl
glycogen reserves broken down-glycogenolysis
• epinephrine, growth hormone & glucocoricoids fat mobilization-adipocytes lipolysis fatty acids + glycerolglucose
• as glucose reserves continue to decreasegluconeogenesis using amino acids & lactic acid begins
• fat undergoes beta oxidation acetyl CoATCA cycle ATP used in gluconeogenesis or converted to ketone bodies which can be used by peripheral tissues for energy
Post Absorptive State Regulation• hormones & sympathetic
division of ANS• blood glucose levels
decreasepancreatic alpha cellsglucagon liver (primary target increases glucose in blood from gluconeogenesis & glucogenolysis
Post Absorptive State Regulation
• low blood glucose stimulates sympathetic nervous systemincreases output epinephrine (neurotransmitter)glycogen breakdown
• sympathetic nervous systemincreases outputadrenal medullaepinephrine & norepinephrinelipolysis
Metabolism Overview