70-80% glucose used by brain

Adipose tissuetakes up fatty acid/glyceolstorage cell

Muscleconsumermuscle proteinsusing FA/ketone bodies/glucose/producing ATP
Kidney
ketone bodiesend up in urine
only organ which has capability of Glutamineammoniaurine
capable gluconeogenesismaking new glucosesmall portion
Brain/ neuronal cells have no beta-oxidation because they cannot absorp long chain fatty acids
(myelin!)
Brain relies on glucose, only backup is ketone bodies
SugarAmylose/lactose/sucrose

Digestion of carbohydrate
Salivaamylasedigest carb
Stomachamylosecut into small pieces
Small intestinepancreasamylase
2 or 3 molec glucose membround bound
emzymesfinal cut
Fiberno enzyme to digestleave the body as
feces
Starchpolymer of glucose moleculebranch
Amylaseproducesmaltose/isomaltose/
trisaccharides/alphe-dextrins
sucrasesucrose
isomaltaseisomaltose
last step at the membranetake up the carb

energy drinkhas isomaltoseno peak of

insulinsteady supply
cocacolabody wants to store energy
Hydrophilic and charged
there are specfic transporters to take up glucose
induced fit
downsideno energy involvedcan work in both
ways
Active transporter
after meal very high conc of glucose in intestine
form of potential energy
sodium/potassium pumpATP as source of nrg
co transporterbinds to glucosecobinfing sodium
Lactosehealth problems
Lactose intelorancepuffy/cramp
intestinalmissing Lactase
Drinking milk after weening period
unnatural
Stop processing after 3 years of age
Caucasianslifelong tolerance
Cells cannot take up lactic acid
Influx of water into intestinal tract
osmosis
Bowel movementstart to interfere with
other dietintestinal tract not acting
normal
end up with diarrheadehydration
many pre-proccessed foodhave
lactosediet product

Galactosemiababies unable to take up galactoselethal disease

mutation in 3 galactose metabolizing emzymes
Liver problemscan go blindfemales can be infertile
Fructose
sugars in ring structure5 carbon
GLUT5-fructose transporter
fructose kinase
mutations in fructosesevere baby troubleliver failureleathal
Fiberno enzyme in human body to degradeleave the body as fecesuntouched
Blood glucose homeostasis
Glucagon/insulinpancreas
Body buildersinject
themselves with insulinto
build more muscle
Pancreas
Glucokinase high Kmlow
affinity for glucosesensitive in
its activity to changes in glucose
level
after mealhigh glucose
glycolysis speed up
increase in ATPinhibits
potassium channelstimulate
calcium ion channeltriggers
release of insulin filled vesicles
producing Insulinnot secreting
once high glucoseinsulin
vesicles start fuse with
outermembrancerapid
response
glucagonalpha cells
respond to insulin
Arginineno glucose
glucagon activate
gluconeogenesis
AA has to be used in
gluconeogenesis
Pancreas-sense glucose and
send out hormones
Only liver releases glucose back
into bloodstream

Why is the sensing done by pancreas?

glucose sensing is difficult for organ making the glucose
itself==locally measure
Brainglucose sensingas back up
glucose in the liver is not representative for the rest of
the body
extremely high in liver
UTPglycogen synthase
prevents glycolysis in the liver
Liver has specific taskkeep glucose level constant
other organs/tissuesuse for their energy
Insulinopposite of glycogen
signaling insulin reponsesmall amt of insulinwidespread of enzyme
Phophatase becomes inactive
Fructose 2,6 bis P allosteric regulator
Fructose 1,6 bis P activator of pyruvate
Combines internal/external control of PFK1
activate fructose 2,6 bis P
Insulin activates PHmore acetyl Coaproduce citratestore nrg in form of FA
Glucagon inactivates PDHglucose to gluconeogenesis
Diabetes Mellituslow insulinstart using
organ tissueheart tissue doesnt grow back
lethal

Digestion/Procession of fats
Non water solubleTriglycerol3 FA attached
Intake of fatliver can synthesize FAfrom
glucose/AA
Unlimited way of storing energy
Extreme obeseheart has to pump blood to all
tissuescan lead to heart failure
Pass digestive tract without touching small
intestinemixes with bile acid-(from liver to gall
bladder)dissolve fat droplets into micelle
containing triglyceridehydrophilic coverbile
acid
Pancreasenzymelipase/colipase break
down
Monoacylglycerolwater soluble
taken up by intestinal celltake up free FA
2-monoacylglycerol
within intesstinal cellresyntheszed back to
triglyceride

Instinal cellschylomicrons/triglyceride/cholesterol/transported to lymph!

Passing of all these fats close to the heartthen into bloodstream
Cholatesoapy substanceprimary bile acidmaking it better water soluble
Cholic acid
glycholic acid
taurocholic acid
Phospholipaseenzyme breaks open hydrophilic shellColipase binds to enzymebreak
open the shell of lipid droplet
Active sitehydrophobicshielded from the water by lidprevents hydrophobic parts to
interact with each otherkeeps the protein in solution (end up with precipitate of protein)
Sucks hydrophobic molecules ininteract freely
Enables enzyme to start cleaving
Degrade triglyceride/phospho
lipdsusing cholate
moleculesend up with
cholic acid
Ileumreceptors bind to
cholic acidbile acids are
sent back to liverrecycled
and stored in gall bladder
Gall bladderstorage of
cholic acidready to be
released when needed

Costs nrg to digest fat

Active FA using ATPadd coenzyme A
Need phospholipds/protein/ ApoB-48done in ER
ApoB48accumulate phospholipidssuck up all the triglyceridessend to golgifurther
maturated then secreted into lymph vessels to the blood
Efficient way of transporting Triglyceride
Hydrophobic insidephospholipid bilayer
Hydrophilic outsidedoesnt seperate in water
Chylomicoronsmake up the most composition is triglyceridecompletely bypass the liver

 Passing capillariesreleased by LPLtaken up by muscle cells

or adipose tissuestoredglycerol back to the liverto make
triglyceride again
Chylomicron remnantsall the triglyceride has been taken up
remaining cholesterol/protein apob48can be digested by the
liver to release AA
Liver has receptors for Chylomicron remnantsto be processed
into cholesterol and AA

Absorbed fats bypass the liver!! why??

Liver is decidingglucose/AA excessgoing into FA synthesis
Futile cycleif triglyceride go into liverwaste of energy
Into FAtake upreassemble into triglyceridemake protein to
transportlosing nrg
Triglyceridefirst use is storagelet the liver decide what to
do with glucose/AA
when there isnt enough FA can be released
Excess carbohydratemore than what one needsrest is used
to make FAmake phospholipids/store as triacylglycerol
Cholesterol>cholesterol estersreservoir inside of lipoproteins
Most cholesterol comes from synthesis in the livertherefore
higher percentage in VLDL/IDL

Why do they have Apo

proteins?
All made up of phospholipids
without apoproteins you
cant recognize the difference
Interstinal tractstop codon
is introduced
ApoC/Emade in the liver
transferred to chylomicrons
ApoCcolipase for LPL
Excess AA/glucose
made into VLDL in liver
transport through bodytil FA
is beng taken outconvert to
IDLtake out more
triglycerideend up with LDL

VLDL/DIL/LDL same speciesbody keeps taking out triglycerideends up in LDLonly

cholesterol degrading in lysozomesreleasing in cholesterol/glycerol/FA

LipoproteinONLY difference is the percentage of compositions

Fasting state
adipose degradetriglycerolsreleasing FA
FA used by muscle cellsfor energy
liver cellsfor ketone bodies production
Glycerolto make more glucose
Lipid metabolisminsulin and glucagoncontrolling the metabolism of these lipids
after mealnormal mix of lipid/AA/glucose
high fat mealtaken lots of glucose means high insulin
to store in adipose cellscant make glucose-3 phosphatethey have to take up glucose to
make glucose-3-P in order to make triacylgrlycerol
Only when insulin level is taken up glucose to store glycerol
Vice versa
betweeen meals glucagon drives
Receptor on adipose cellhormone sensitive lipase
PhospohrylatedFA and Glycerol released into bloodstream
Insulin driving the storage of triglycerideglucagon is driving deprivation of triglycerol
also driving glucose and ketone bodies in liver
VItamin B6required in the
synthesis of serine, alanine,
cysteine and aspartate
Vitamin B6PLPneeded
for Transaminases break
down AA as a cofactor
needed as a cofactor for the
enzymes that allow selenium
to be used from the dieatary
form

DIgestion of Proteins
Enzyme regualtion
activation by limited proteolysis of dangerous
proenzymescomplete on/off regulation

protein broken down into Amino Acids

building biological substances

Proteases=proteolytic enzymesbreak down dietrary proteins into AAin stomach/intestine

Zymogensynthesized, inactive, digestive proteases
Stomach
Gastric HCldenaturation of proteinsproteins to metaproteins
activates pepsinogen to pepsin
makes pH in the stomach suitable for the pepsin
pepsinprotein digesting enzyme of the stomachbreak peptide bonds polypeptides
chains of amino acids linked together
Small intestine
pancreatic enzymes
Trypsin/Chymotrypsin/Carboxypeptidase/Elastase
break down polypeptides
TrypsinPancreatic JuiceEndopeptidase
hydrolyzes central peptide bond
secreted in an inactive formtrypsinogen
optimal ph is 8
activated by enterokinase enzyme then by autoactivation
ChymotrypsinHydrolyzes central peptide bond
secreted in an inactive formchymotrypsinogen
activated by trypsin
Elastase
secreted in an inactive form called proelatase
activated by trypsin
digests elastin and collagen
Carboxypeptidadse
hydrolyzes terminal peptide bondcarboxyl terminus of the polypeptide chain
secreted in an inactive formprocarboxypeptidase
activated by trypsin
Duodenumvia pancreatic duct
Brush border enzymesmicrovilli of the small Intestine
enzymes
peptidessmaller units2 or more amino acids
Active processneeds energy
1.Carrier proteins transport system 1:1 ratio
energy needed is derived from ATP
Absorption of one amino acid molecule needs one ATP
molecule
7 carrier proteins, one for each group of AA
each carrier protein has to site one for AA and one for Na+
co-transports AA and NA+ from intestinal lumen to cytosol.
absorbed AA passes to the portal circulation, while Na+ come

out of the cell in exchange with K+ by the sodium pump.

2.Glutathione transport system 3:1 ratio
transport AA from intestinal lumen to cytosol of intestinal mucosa cells
active processneeds energyATP
absorption of one amino acid molecule needs 3 ATP molecules
Glutathione reacts with AA in the presence of glutamyl transpeptidase to form glutamyl AA
which releases AA in the cytosolforming 5 oxoprolineused for regeneration of
glutathione for another cycle

Proteins
o Continually synthesized and degraded
Degradation = turnover
o Cathepsins: lysosomal proteases
Degrade proteins that enter lysosomes
Cytoplasmic proteins:
o Targeted/ linked to ubiquitin (small protein),
o preparation for destruction
o Ubiquitin-tagged proteins
Interact with the proteasome: a large protein complex
Degrades proteins to small peptides
ATP dependent
Amino acids released during turnover can be used for synthesis of new proteins/energy.
Cystic fibrosis
o Blockage of pancreatic duct
o Need oral ingestion of digestive enzymes
Kwashiorkor
o Protein malnutrition
o Excessive protein degradation
Body maintains relatively large free amino acid pool in the blood
o Even during fasting
o -> tissues have continuous access to individual amino acids
For synthesis of proteins and essential aa derivatives
Such as neurotransmitters
o Provides the liver with amino acid substrates for gluconeogenesis
o Provides other cell types with a source of fuel
o Derived from dietary amino acids and turnover of proteins in the body
During overnight fasting and hypercatabolic states
o Major source of free amino acids:
o degeneration of labile protein, particularly in skeletal muscle
liver = major site of amino acid metabolism
o and major site of urea synthesis
o major site of amino acid degradation
hepatocytes
o partially oxidize amino acids
converting carbon skeleton -> glucose, ketone bodies, or CO2
o ammonia = toxic, liver converts nitrogen from aa degradation to urea
excreted in urine
nitrogen derived from catabolism in other tissues

transported to liver as alanine or glutamine

converted to urea
branched chain amino acids (BCAAs)
o valine
o isoleucine
o leucine
o oxidized in skeletal muscle
and other tissues, BUT not in the liver
o in skeletal muscle:
carbon skeletons and some nitrogen
-> converted to glutamine
Released in the blood
Remainder of nitrogen incorporated into alanine
Taken up by the liver
Converted to urea and glucose
Protein functions:
o Transporters of hydrophobic compounds
o Cell adhesion molecules that attach cells
To each other
To extracellular matrix
o Hormones that carry signals
o Ion channels through lipid membranes
o Enzymes that increase the rate of biochemical reactions

Protein Structure
Sturucture determines the function
build up of the protein
20 amino acids
nonpolar-neutraldont give much to protein
chargedgive charge to protein
OH groupscan be phosphorylatedsignal molecules
Prolineknick in protein structure
to couple AA into proteinmake peptide bondrelease of waternrg consuming process
Lots of nrg to make proteins
Properties determined by side chains
peptide chain = amino acids linked through amide-bonds
Protein foldinginstant
big quality control in ERcheck whether its folded correctlyif not try again and degraded
folding occurs in most energetically stable formpolar will go outsidewater environment
hydrophobic will go inside

Alpha helix
it forms a helixlong rod shaped side chains on the outside
find in anchor proteinin membrane
can form pores through which nutrients/ions can pass
hormone receptors

collagenrigid structureboat rope3

intertwined alpha helices
helices < fibril < fiber
collagens can be interconnected with each
other
protomer/dimer/collagen tetramer/
suprastructure
Ehlers Danlos syndromerubber man
syndrome
whole metabolism of collagen gone
wrong
mutations in fibrous proteins and
enzymes
loose joints
1 in 5000
PLOD1= lysyl hydroxylase
joints, bone, bone cells,
AA sequencemutationchange in AAhelix breaker
COL5A1/COL5A2skin
COL3A1blood vessels
small blood vesselsupply nutrients/oxygen to endothelial cell is compromised
Elastin
bundlestretch out and returnsrubber band
single cross link
blood vessel wallmix of collagen and elastin
cysteinedisulfide bondestra structure for the proteinfixes the 3D

Beta sheet
flatline up next to each othercan be combined in one protein
lysozymealpha helix and beta sheet
Prion diseasecreutzfeld jacobmad cow disease
Change in structurealpha to betaresults in protein precipitates in brain
can escalatemore wrongly folded proteinconverts normal proteins
3D structurecombination of all structure

Quaternary structure
multiple structures come together to form one protein
contatin coenzymes/help molecules
hemoglobin
4work together to bind the oxygen
T stateR state

Connective Tissue
Proteoglycanattached to laminine
Glycoproteins-almost 95% proteins have glycan
Glycosyltransferaseadds more proteinadded one after the other
Starts in ERblock then trim and addcontinue in Golgi
Vitamin E binds to radical itselfprotect AA from ROS damage
VItamin Ccan bind to radicalsscavengerimportant as cofactor for enzymes that
make collagen
For the collagen molecule to aggregate into its triple-helix config selected proline residues
must be hydroxylatedrequires di-oxygenase enzyme,alph KG, reduced iron, ascorbate
Scurvybleeding gumswoundslacking of vitamin C

low vitamin c =
low collagen
Selenocysteine is
an essential
component of the
enzyme
glutathione
peroxidase

Glutathionperoxidasedetox organic peroxidase using

glutathion as coenzyme
suppresses the oxidative stress by converting oxygen free
radicals into less/non-toxic forms
Change in structure = change in function

Breathing
ATPallosteric regulator
Oxydative energy is converted to ATP
Via Acetyl CoA food is converted to CO2 and water
more ATP = faster speed of ATP = more oxygen in mitochondria
amt of oxygen going down = at rest
Need contant supply of oxygen to keep all the matabolic pathway
going
oxygen transport by red blood cell

why red? Metal IonIronproducing red colornot freely available

heme groupIron binds O2

why so complex? rustcontact btw iron and oxygen will destroy the
property of red blood cell
to keep iron in specific oxidized state prevent from forming iron
oxideto keep iron in its correct form
heme groupbinding oxygenreleasing is difficult
globin proteinmuscle cell
myoglobinred blood cell
complex the same group in specific way
quaternary structureheme group can be in two conformation
T and R by allosteric
binding site is shielded from wateronce O2 is bound it will not
rebind
binding of O2 affects affinity for next O2slow to high affinity
change of conformationby heme group
reverse is true
myoglobinskeletal muscle onlyaffinity is too high to supply oxygen to tissues
backup!!

speed of bindingself regulating

another back up systemcompletely run out of oxygen
anaerobic regulation kicks in
2 ATP produceddepletion of glucoselactate produced
CO2skeletal muscle back to lungsto breathe out

why is CO2 dangerous?

bubbles will start to form in blood vesselsno supply
of glucosecells will die
Iron cannot bind to CO2only 10% transported as CO2
CO2 with carbonic anhydrase> carbonic acid>
converted to Bicarbonate immediatelybody will not
form bubbles
bubbles=carbonic acid(spa red)
more muscle movementmore acid produced
BicarbonateBuffering of pHhigh/low CO2/will not
affect PH of bloodequilibrium will remain
pH is independent from amout of acid produced/not
produced

red blood celltransferring proton!

protein binds proton
In lungsoppositereformed from portons and local bicarbonate
picks up proton from acid and reforms CO2pressure in the lungs alveoli is higher
Bohr Effect
more strain > more acid > more O2 release
lower the pH in bloodtissue and proton
binding and release is completely controlled

why breathing fast after stopping excercise?

enormous lactic acid in skeletal muscleto get rid of all the CO2control the rate of
breathing not amount of oxygen you need
Draining the acid leads to gasping

Flava beanssuperoxide moleculesdestroy oxygen binding property in hemoglobin

oxygen radicalsdangerous
producing large amounts of glutathionphosphate pathway shunt to supply NADPH
cytochromeB5
G6P dehydrogenase deficiency
RBC have shorter half life
PPS does not workcannot produce NADPHdont have mitochondriatherefore
cannot reduce glutathioneHeinz bodies formred blood cells composed of denatured
hemoglobin
hemoglobinprecipitatecompletely unable to transport
increase oxydative pressureprovoke hemolytic shock
antimalrian drugs also provokeso do it in hospital
Flava beans/Infectionsactivation of immune systemlarge amout of radicals
aging is also problemproteins dont work perfectly
thalassemias: anemia due to unbalanced synthesis of alpha and beta chains of
hemoglobin

Yellow baby syndrome

hemoglobin is released into blood
globinmight be digested back to AA
no enzyme that can break downHeme group with Fe is very toxic
potent catalyserproducing reactive oxygen
livercouple to something that makes it more solubleUDP glucoronatedissolved in
bile

detergent from bileperfect to dissolve

hydrophobicgarbage bin
hydrophilic goes through kidney
high number of blood cell
liver is not maturedinsoluble hemoglobin
body depositing it to skin and brain
Babies put under blue lamp
Erythropoietincontrolling the rate of RBC
formation in bone marrow
oxygen tension lower in high altitude
Cyclistproduce more RBCperform better
Inject with Erythropoietinincrease in RBC

why does breathing change for DIabetes

patient?
getting rid of Acetone
insulin shockketone bodies
ketoneacidosisproducing more acid
lower pHproduce protonsgetting rid of it
by breathing
too much acid = breath out more CO2

During hyperventilation why bag over your mouth?

during hyperventilationtoo much oxygenbreathing out too much CO2/acid
pH can go upbrain doesnt like itcan go into coma
CO2 should be inhaled back inkeep the pH neutral
EPO used by cyclist
normal in human bodyby kidneysmaking it difficult to test (armstrong)
O2 determines number of epo
EPOcontrols the production of RBCtreat anemiaused after chemo/radiation to increase
bone marrow
Glycosylate
outside is sugar structure
glycosylationcell type specificdifferent enzymes in different organs
species specific
immogenicstart destroying foreign bodies
far less efficient than actual human EPO
reasonlivergets rid of toxicbind to foreign substance
consistent injection requireddue to short half life
receptor bindingnot only for clearancenot a good binder to bone marrow receptors
not a good receptor in liverto have better half life

Alcohol and metabolism

lipid damageliver failure
Fatty liverreversiblefat depositscause liver enlargement stop
for 3monthsperfect recovery
Liver fibrosisrecovery possiblescar tissue remainslipid
cells will turn into connective tissue/forming scar tissue or fibroblasts
liver can regrow
cut 1/4 of liverthen within 1year it will regrow
Cirrhosisirreversiblegrowth of connective tissue destroys liver
cellscauses shrinkingless liiver cells
Triglyceride/adipose tissue in Liverabnormal
Acetyl-CoAbuilding block of Triglyceride
ethanolclosely related to acetyl CoA
fruit-ripeningsmall amount of alcohol
Ethanol Alcohol dehydrogenase> Acetaldehyde=toxic Acetaldehyde dehydrogenase>
AcetateAcetyl CoA synthetase> Acetyl CoA
generated some energy-NADHto ETC
Ethanolefficient way of generating energylose their appetite
Acetaldehyde/acetate in cytoplasm
Acetate goes into bloodtissue picks up acetate to make acetyl CoA
acetatepreferred
very good food substancereason why people who drink a lot are very thin
acetaldehydegives you the headache next morningintestinal cellsvomitting
binge drinking/too much
NADH has to be recycled
alcohol dehydrogenaseNAD+ to metabolize alcohol
more alcohol=overload of NADH in cytoplasm/mitochondria
NADH to be used in ETC in mitochondriatoo much so mitochondrai doesnt need it
burning ATP and ETC will stopresulting in high amt of NADH
In liverrecycle NADH back to NAD+ by lactate dehydrogenase
TCA cycle will also stopused to make FA instead
lactate used first then citrate is being used for FA synthesis
pyruvate dehydrogenase will stop working as wellbecause NAD+ is being used by alcohol
so end up with pyruvatewhich make lactateand to get rid of NADH into NAD+

Korsakov syndrome
alcoholvitamin B1 deficiency
chronic alcohol diseaseintestinal tractblocks uptake of vitamin B1
lead to excessive production of lactatekill brain cellsalzheimer like syndrome
Intravenous injection of vitamin B1 solves
brain still needs glucose
liver tries to make glucoseusing AAmetabolized by liverAlanine is put into
pyruvate
pyruvate is going straight into lactatenot into gluconeogenesisby excessive amt of
NADH
backupketone bodies
degrade adipose tissue/skeletal muscle
use glycerol to make glucose
FA>ketone bodies for brain and muscle cells
high amt of alcohol in short timepumping out lactic acidketonebodiescoma
similarly to ketoacidosisdiabetic patient who forget to take insulin shot
body has some defense!
heavy deep breathinglacto/ketoacidosisbreathing out much CO2 as possible
protons coming from acids

Eating lots of carbs before drinking?

liver will start storing carbs as glycogen
all the glucose that your brain needs is coming from glycogengluconeogenesis not needed
no ketonebodies
you can train liver
alcohol dehydrogenase
mutationcannot metabolize alcohol/extremely slow
in caucasiansecond enzyme system-MEOS-microsomal ethanol oxidising system
ethanol-acetaldehyde
metabolyze fast/efficientmake massive amt of acetaldehydetoxicdestroy the liver
very fast
1.acetaldehyde=toxicinteract with DNA/proteins
main cause why alcohol induces/risk factor for liver cancer
2.MEOScytochrome P-450always in the liverdetoxify toxic agent
but! uses electrons from NADPH reduce agentsalcohol
high nrg electrondirect with oxygenreactive oxygen species develop
destroying liver FAST!
Urea cycle affected
damaging enzymes by acetaldehyde and oxygen species
to get rid of lipidsapo lipoproteinsto get rid of themsecreted to get lipids to adipose tissue
rapidly damaged by acetaldehyde
liver makes more FA but cannot get rid of it
reason whyliver looks like adipose tissuestore triglyceride/cannot secrete
abstinence!! protein can be reformedthen export triglyceride from liverweeks to
restore

alcohol direct alters drug metabolism

xenobioticsmake it water solublekidney gets it out in urine
hydrophobicput it in bilethrough feces
Liverwants to get rid of foreignbecause of half lifetaking pills in regular interval
3substances to make it more hydrophilic
drug is not affective anymore
glutathionehydrophilickidneys take it out in urine
UDP-glucuronic acidstuck on different moleculehydrophilicthrough feces
PAPSstuck on xenobioticsthrough feces
morphinehydrophilic
30% glucoseused throguh pentose phophate shuntNADPH is needed for FA
synthesis

NADPH is needed to constantly make sure sufficient glutathione for detox/getting rid of
oxygen radicals
heme grouphydrophobicput it in bile and secrete in feces
cytochrome P-450high amts in liver
CYP2E1induced if large quantity of alcohol is taken
specific range of molecules to metabolize
toxic substance becomes less toxic
converts paracetamol into toxic compound
depletion of glutathion increases ROS damage
block of enzyme acetaldehyde dehydrogenase inhibitor
take away urge to drink againextreme vomiting
Blood coagulation
damageplatelets activatedblock the hole in blood vessel
then blood coagulation
catching all blood cellscab
extra carboxyl groupby vitamin Konly in the liver
bleeding disorderin alcoholicsGla doesnt function properly
vitamin Kantagonistsused for thrombotic problemsblood clots in artiery/veins
warfarin/dicoumarolprevent excessive blood clotting
problem with VLDL-fatty liver
induction of MEOSdrug metabolismreactive oxygen damage
problemic on reducing glutathione
ETC /damage DNA/ liver tumors/down in protein secretion
measuring without biopsy?
only during liver damage
hepatocytes break open
efficiently measure these enzymes
can be detected easily by detecting these enzymeshepatic disease
kupffer cell-localized tissuer macrophages
activated kupffer cellsTGFbetaactivate
stellate cell(vitamin A)make massive amt
of extracellular protein>fibrosis/scar
tissue to replace hepatic sites

Muscle Metabolism
Different types of muscle fibers
Type 1marathon/long distance
contracting rather slowlyuse oxydative
phosphorylationredhigh myoglobin
contentincreased concentration of
capillariessufficient oxygen delivery
Type 2sprint/short distance
contracting fastexhausted in short time

appear whiteenormous amt of glycogen grains(white)low mitochondrai because

anaerobic glycolysis is used
Different muscle types have different phenotypes
Skeletallong fusedlong fiberscontract over long distance
Heartshorter cellsconstant short movementinterplated discs
Smooth muscleblood vessel/intestinal tractcell itselfcontractsfixing itself in certain
position
Contraction
actin and myosin
each strokeone ATP is used
release-flex-rebind-reflex
shift of myosinpossible movement of muscle cells
ATP is not stablewants to hydrolyze immediately
each strokewill burn one ATP
amount of ATP in muscle is relatively constant
metabolism has to speed up to keep generating ATP
AMP changes alotregulating metabolism
ATP is depleted AMP is increasingphosphofructikinase will be activatedhigher speed
of glycolysis
muscle glycolysis vs liver glycolysis
Speed is independent
PFK1 in muscle cell is different than one in liverinsensitive to insulin/glucagon
does not control rate of glycolysis in muscle cell
muscle cell do not have glucagon receptor-it has epinephtrine-fight or flight
epinephrine receptor-activate adenylase cyclase
EVEN BEFORE THE MUSCSLE IS CONTRACTED, there is high rush of adrenaline
muscle will degrade glycogen so glucose is already there to be metabolized
prime cell for movement
Rapid signal transductionhormone is different from liver
PFK/pyruvate kinasemain enzymesallosterically inhibited by ATP
muscle at restreservoir of ATP shuts down glycolysis
hexokinase!! in musclealways active at low glucose conclow Km
negative feedback on hexokinaseprevent G6P to build up
at excercise
increase of ATP
AMP is alloseteric activator
glycolysis will speed up to make pyruvate/ATP in mitochondria/not sufficient oxygen delivered
to produce more lactate
oxygen has to be delivered to muscle cell
trainingrewire arteries/capillaries so more and more oxygen can be delivered as soon
as excercise

sprintheart rate does not go up yetheart/blood vessel contractedit has to pick up speed/
expand fast
pyruvate>lactate = complete rest>blood cannot deliver sufficient oxygen
hemoglobindelivers oxygen
muscle cellhas myoglobinreservoir of oxygen in muscle cellonly used when
depletion
heme group with Ironred color
red meat vs white meatred meatmuscle cells are rich in myoglobin
chickenwhite meathardly any myoglobin
myoglobinnormal affinity for oxygenbut much too high for hemoglobin to operate
quaternary structurefixing moleculeslowers affinity of Fe for Oxygeneasier to
release to cells
once hemoglobin is depletedoxygen pressure will go downmyoglobin will release its
oxygenOXPHOS
slowly contracting muscles-aerobic
red meatrisk for intestinal tumors
Bohr effectpH goes uphemoglobin will release its oxygen better
sprintnot using oxygengetting rid of acid produced
reasoneach stroke of muscle fiber takes one ATPin the endspeed is determined by
speed of generating ATPthe rate of ATP can be produced
Anaerobic glycolysosmuch faster at generating ATP
rate limitingrate at which u can make ATP
Rate of ATP production = final world record is already measured
interval training> train to have more mitochondria
tricks the cells
Creatine phosphateATP storage in musclespecific in MUSCLE cells

stores increase with

training/excercise
double storage of ATP/
can work in both
direction
Creatine <> creatine
phosphate
very fastalmost
instantaneousgood
for athletes
kidney>
guanidinoacetate>liver
>converted to creatine>into bloodstream>taken up by muscle/brain/heart
nasty!CP has high nrg electronunstable!spontaneoulsy cyclization>creatinineend up
in urine
lost ur nrg!! supplement is not really helpfull
it shuts down bodys own creatine system
creatine supplementgood for short time period sportsnot ideal for long distance
Muscle cells DO NOT have glucagon receptor
HAVE epinephrine
sprinters hitting themselves before startgenerate adrenalinespeeds up liberation of glucose
from glycogen
muscle stores glucose only for its own useinsulin needed
lots of carbohydratemuscle cellglucose transporter on membranesuck up lots of glucose
form meal.
muscle cell lack G6P!
cannot make glucose out of the cell
ONLY be used when muscle is
excercising
Liverglucose production for brain
function
too slow for use in muscle
AMPon/off switch10 fold
increase in muscle cells when it
contracts
muscle cells adenylate kinase
stable to take 2 ADP to make one
ATP and one ADP
rate of glycogen and glycolysis
Aerobicwhy is it slow?
NADh has to go into mitochondria to
generate ATP
anaerobinc is faster!NADH in

cytoplasm is constantly recycled to make lactate

even though delivers 2 ATP instead of 36its extremely fast!!!
lactatenot waste product!
Cori Cycle
muscle cellslactate is perfect substrate for gluconeogenesesto make new glucose
export back to muscle
liver is using oxygen to generate more glucose to be used fast
heart muscleuse lactate rather than glucose during sprintpyruvate>aerobic
always high O2 blood from lungs
muscle contractionspeeds up
glycolysis
Epinephrineindependent of
feeding/already in moving or not
cAMP activate glycogen
phosphorylase
Nerve impulsethrough Ca2+
signal for contraction for actin/
myosin
calcium calmodulinused
through epinephrinebinding to
its receptoralpha adnergic
receptor
beta blockers in heart patients
only affect heart
skeletal muscle has alpha receptor
only heart cell has beta receptor
after used up muscle glycogen
muscle switchisoenzymeAcetyl
CoA carboxylase in muscle
different function
muscle cells do not synthesize FA
malonylCoA inhibits FA import in to mitochondria
controlled by AMP
low glucose/high AMP>activates AMP kinaseactivates Acetyl CoA carboxylase
degrades malonyl coa into acetyl coa> FA will start be using in mito
In order of usage
Glucose>ketone bodies>FA