Transcript METABOLISM & - Doctor Jade

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
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Nutrients
metabolism requires nutrients
– ingested chemicals needed for growth,
repair or maintenance of body
obtained through ingestion & digestion
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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
• ATPADP + 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
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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
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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
moleculesmacromolecules
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 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
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
• Glu6PO4isomerizedFru6P+
ATP  fructose-1,6-bisphosphateFru 1,6diP
• reactions use 2 ATPs
• Energy investment phase
ATP
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
Glycolysis
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
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
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
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
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 acceptoroxygen
• 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
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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+)
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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
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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
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 proteinATP
synthase attaches PO4 to ADP ATP
ATP
synthase
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
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 3=24 ATP
– 2 FADH2 X 2=4 ATP
• 2 moles pyruvate2 NADH +
H+-glycolysis 2 X 2 = 4 ATP
• Total 36 ATP
Carbohydrate Biosynthetic
Reactions
• anabolic reactions
–small precursor
molecules
macromolecule
synthesized
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
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 sourcetriglycerides
– 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 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
• 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
Glycerol Oxidation
• converted to
glyceraldehydes 3-PO4
(a product formed
during glycolysis)
• ATP-not neededconverted 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 succinylCoAKrebs 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
molecules2 acetyl coA
molecules which can enter Kreb’s
cycle
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
Lipid Metabolism
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
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
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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
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)
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
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
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
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
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 downglycogenolysis
• 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
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
Post Absorptive State
Regulation
• low blood glucose
stimulates sympathetic
nervous
systemincreases
output epinephrine
(neurotransmitter)glycog
en breakdown
• sympathetic nervous
systemincreases
outputadrenal
medullaepinephrine &
norepinephrinelipolysis
Metabolism Overview