BCHM Facts-PreMid

• Arsenite- most toxic form
• Acts on enzymes containinglipoic acid (ex: PDH, glyceraldehyde 3 phophate dehydrogenase) Reoxidizes the reduceddisulfide bond --> increases its stability so pyruvate and lactatebuilds upCauses a decrease in E.production ---> acidosis Treatment: 2,3 mercappropanol(competes w lipoic acid)

• Deficiency in thiamine
• (vitamin B1) results in PDH complex E1 not being able to decarboxylate
• pyruvate because the enzyme will present as an apoenzyme with no thiamine
• pyrophosphate cofactor bound to it

• Mild deficiency: GI
• complaints, "pins and needles"/burning feet
• Severe deficiency: Beri-Beri
• or Wernicke-korsakoff Syndrome

• Asia- eating polished rice with husk removed (source of thyiamine)
• Wet and dry type- depending
• if edema is present or not
• Nueromuscular cardiovascular
• disorders, delirium, memory loss, muscle weakining, increased venous
• return to heart, peripheral vasodilation, opthalomogplegia
• Death by high output cardiac
• failure

• Chronic Alcohol abuse and poor nutrition
• Wernicke's encephalopathy(acute phase): delerium, mental derangement, ataxia, opthalmoplegia
• Korsakoff psychosis (chronicphase)- anterograde amnesia, distinct pattern of brain damage (focaladhesions) …IRREVERSIBLE
• Diagnosis- urinary thiamineexcretion, transketolase activity in RBC, lactate/pyruvate levelspost-oral glucose pill
• Treatment- thiamineinjections intramuscularly (before chronic phase)

• affects complex I
• Optical nerve damage - lossof bilateral vision
• passed onto all offspring

• Mutation in tRNA for lysine (encoded by mt)
• Late childhood -->
• adulthood
• Myoclonus- uncontrollable
• muscle jerking
• Seizures, lactic acidosis,
• dementia, cardiac problems
• Ragged red fibers = clumbs of
• enlarged mito

"lactic leucy"

• Mutation in tRNA leucine
• 5-15 yo age onset
• Stroke
• Lactic acid - vomiting,
• tiredness, muscle weakness

"12 GENTlemen with STREPthroat"

• Mutation in 12s rRNA
• Streptomycin and gentamysin
• binds to 12s rRNA
• No translation of ATP
• synthase

plant toxins- deplete ADP, shuts down ETC, but reactivated w uncouplers

Atracyloside (mold toxin)-acts on cytosolic side

Bongkrekic acid- acts onmatrix side

• -chemical uncoupler
• Benzene ring w 2 nitro groups
• and a dissociable H+
• High [H+] in intermembrane
• can add to deprotonated 2,4 DNP
• Protonated (uncharged) form can pass through membrane into
• matrix
• H+ is released into matrix

chem uncoupler

• Antibiotic that makes inner
• membrane permeable to K+
• No proton motive force, but
• proton gradient remains (?)

• chem uncoupler
• orms non-specific
• channel that allows H+ to pass through

• prevents donation of
• e- from Fe-S to CoQ

• prevents e- donation
• from complex III to cyt c

• Build up of reduced
• compondents of all complexes

PEP --> pyruvate [bypassed with pyruvate carboxylase]

F6P --> F16BP [bypassed with F16BPase]

Glucose --> G6P [bypassed with g6pase]

Remeber- the 1st, exact middle, and last steps of glycolysis are irreversible. Must be bypassed in gluconeogenesis to go from pyruvate --> glucose

• Type I liver glycogenosis
• G6Pase enzyme defect

• Affects liver, intestinal
• mucosa, kidneys
• Failure to dephos. =
• hypoclycemia & hepatomegaly
• Most common glycogen storage disease
• Lactic
• acidaemia-
• glucagon enhances lactate production
• Hyperlipidaemia

• Type 1B- deficient in G6P
• transporter (same results)

• Avoid fasting
• Uncooked
• cornstarch
• Nasogastric
• tube- to infuse
• CHO when sleeping

• Type III liver gluconeogenesis
• amylo-1,5-glucosidace debranching enzyme

• Affects liver, myocardium,
• skeletal muscle
• VERY MILD
• Glycogen molecule has
• abnormal structure w short outer branches
• Unable to metabolize beyond
• branch points
• Hepatomegaly, myopathy,
• asymptomatic hypertrophic cardiomyopathy in elderly

• Type 4 liver glucogenosis
• -branching enzyme defect

• -severe and fatal
• -liver cirrhosis
• -glycogen has long unbranched chains so not soluble
• -very rare
• -autoimmune attack on tissues
• -treatment: liver transplant

Type 6 Liver glycogenosis

• - defect in liver phosphorylase
• -hepatomegaly and hypoglycemia

defect in hepatic glycogen synthase

• -unable to synthesize glycogen at all
• -fluctuates b/w hypo and hyperglycemia

-lysosomal alpha 1-4 enzyme defect

• -generalized glycogenosis (liver, heart, muscle)
• -lysosome overstuffed with glycogen
• -affects brainstem and spinal cord
• -infants- severe- die in less than a year
• -juvinille and adults- moderate

• Enzyme deficiency is muscul phosphorylase
• -elevated CKMM levels- caused by muscle dystrophy and proteolysis
• -myoglobinuria- brow/red urine
• -myocytes become damaged due to glycogen buildup
• -cramps upon exercising

• treatment: High protein diet,
• creatine supplements

Defect in PFK1 enzyme

• -
• Muscle weakness and cramping
• Hemolysis can occur due to low PFK
• acvitivty in RBCs

• (CGD)- Phagocytes have a defective NADH oxidase so they cannot produce
• superoxide anions to combat infection (usually caused by beta subunit)

• Causes recurrent life
• threatening bacterial and fungal infections
• Granulomas often found in
• skin, GI tract, urinary tract

• Granuloma- collection of
• macrophages (often presents as
• trouble breathing)

- reverses (dismutases) of superoxide back to O2

• O2- --> H202 (not toxic
• unless converted to a toxic species)

• Releases oxygen for the
• conversion

• Cytosolic isoform- requires
• Cu+ or Zn+
• Extracellular- requires Cu+
• or Zn+
• Mitochondrial- requires Mn+

• Since these are all +
• charged, O2 immediately binds to it

in cytosol and mitochondria

• Reduces peroxide to water
• Reduces lipid peroxides to
• alcohol

H202 --> 2H20 + O2

• Mostly found in liver and
• kidney (b/c that’s where most
• peroxisomes are)

Vitamin E

• Contains tocopherols (AOX) -
• terminates free radical chain reactions of lipid peroxidation
• Alpha isomer- against ROS
• Gama isomer- against RNOS
• (Think Taco = fat = use vitamin E)

Vitamin C- regenerates the reduced form of Vitamin E

• Caretenoids-
• can get rid of oxygen radicals with its long conjugated double bonds

• Scavenges OH radicals,
• peroxyradicals, and oxyheme radicals
• Uric acid is water soluble so
• it can enter the plasma, saliva, and lung lining fluid along with protein
• thiols to scavenge free radicals

occurs when enzyme is fully saturated with substrate, and therefore indicates strength of an enzyme

[substrate] needed to reach half of Vmax

note: small km = HIGH substrate affinity for the enzyme

• Competitive- chemical analogue of the natural enzyme so they compete for the same active site since they will both fit
• same v max, km increases
• easily overcome by increasing [substrate] to have more of it than the inhibitor

• Noncompetitive- works at a different active site
• same kM
• lower Vmax

• pathological: biomarker for bone or liver disease
• physiological: increased during pregnancy and childhood growth

"The people in the ALPs have Paget's Disease"

• CK1- BB- brain, lungs
• CK2- MB - myocardium * (used for heart attack biomarker)
• CK3- MM - myocardium and muscle

• Alanine AminoTransferase (ALT)- liver only
• Aspartate Aminotransferase (AST)- heart,muscles, liver
• Alkaline phosphate (ALP)- bone and liver

*there are others (unimportant)

• CKMB2- most specific
• Myoglobin- most sensitive (fastest)
• Troponin- longest window (3-12 hrs)
• LDH- confirms with 1,2 flip

• Series: product of 1st rxn becomes substrate of the 2nd rxn
• Parallel: energy to drive a specific rxn forward comes from energy released by a side (parallel) rxn

• Uracil Triphosphate (UTP)- carbohydrate synthesis
• Cytidine Triphosphate (CTP) - lipid synthesis
• Guanosine Triphosphate (GTP)- protein synthesis

ATP + AMP --> [AK] --> ADP

• high energy compound in the glycolytic cycle
• normally converts to 3 phosphoglycerate but in RBC it is shunted away to form 2,3 BPG [via 3BPG mutase]
• holds hemoglobin in the T state

• 
• N base @ C1
• Pi group @ C5
• DNA= OH at C2
• RNA= OH at C2 and C3

• small nuclear RNA- used for intron splicing
• micro RNA- regulates genome expresssion through cleavage

• Negative- underwound, left handed direction
• Positive- overwound, right handed direction

Topiosiomerase- cut DNA strands and then reseals them to form supercoils

I- cuts one strand, passes the other through the gate, and then rejoins them. Removes one twist @ a time

II- (Gyrase)- cuts both strands to remove 2 twists at a time

1. nucleosome (8 histones + linker DNA) forming "beads on a string"

2. solenoid- 30 nm fibers formed by many packed nucleosomes arranged on a scaffold/matrix

Acetylation: removes the histones + charge, reducing the affinity b/w histones and its wrapped DNA, allowing the DNA to be free for transcription

Methylation: tightens DNA around histones forming heterochromatin (transcriptional silencing)

5' --> 3'

• Pol I - excises RNA primer
• Pol II - repair damage
• Pol III- elongates primer

• prok- only relieves - supercoils
• euk- relieves + and - supercoils

• Topoisomerase I - can only relax coils
• ----prok- relaxes (-) coils
• ----euk- relaxes (-/+) coils

• Top II (pro)- does everything (intro +/-, relaxes +/-)
• Top II (euk)- does everything EXCEPT intro (-)

Prok: RNA Pol I - binds to sigma factor to make holoenzyme to begin transcription (terminated via rho factor)

• Euk:
• Poly I - rRNA
• Poly II- mRNA
• Poly III - tRNA

• 5' GU donor site (U1)
• 3' AG acceptor site
• middle = A = branch site

U2- forms the lariant structure that is eventually cleaved

• occurs due to adenosine deaminase-- the intron and exon are complimentary to each other so they form a double stranded RNA structure that attracts an ADAR enzyme to it that causes the editing
• without editing the gene woudl conduct Na+ and Ca2+
• with the editing the gene conducts only Na+
• important for memory and learning

• UAA
• UAG
• UGA

[all start w uracil]

start = AUG (Met)

• Preproinsulin- contains a signal sequence that brings it to the ER
• Proinsulin- forms inside the ER when the signal sequence is cleaved
• Insulin- removal of big internal C-peptide, leaving behind the disulfide bonded insulin (the C peptide has the info on how to fold, but once folded is not needed)

anchors lipids to the plasma membrane

• O: occurs in gOlgi .... carb attaches to OH gp (of Ser or Thr)
• N: occurs in RER ...carb attaches to amide N (of Asp)....more common glycosylation, assists in protein folding

P-SOLaA

• Palmitic: 16-0
• Steric: 18-0
• Oleic: 18-1
• Linoleic: 18-2 * w6
• alpha Linoleic: 18-3 * w3
• Arachadonic: 20-4 *w6

essential FA* = anything the body cant produce and is part of the w3 or w6 family (....LaA)

• aka cardiolipin- holds the ETC together
• Barth syndrome- acyl transferase inhibited from converting lysosomal CL to regular CL so lysosomal CL builds up causing cardiohypertrophy

phospholipid where the HC chain is attached to the C1 OH of glycerol (??)

group of lipids that share an initial common pathway and result in 5C isoprene units

• synthesized from 5C isoprene units (that come from polyisoprenoids)
• form sterioids (ex: cholesterol)

• [e sphingolipid]
• location: myelin sheath
• head group: phosphocoline, phosphethanolamine

• [e sphingolipid]
• location: neuronal cell membranes
• head group: galactose

• [e sphingolipid]
• location: gray matter of CNS
• head group: 3+ sugar gp + sialic acid residue

-multiple sclerosis, niemann pick disease

dipalmitoylphosphatidylcholine

• di- dead baby
• palm/toyl - baby w toy in his palm

• Unsaturated: loosely packed due to double bonds, therefore increases fluidity
• Saturated: tightly packed together due to single bonds, and therfore increases rigidity

• H --> L
• simple diffusion
• facilitated diffusion
• protein transport carriers -uni/symp/antiport

• primary: gains energy for L--> H transport via ATP
• secondary: gains energy for L--> H transport via Na+/H+ concentration gradient

• Glut 1 + 3 = brain (low km)
• Glut 2= liver (high km)
• Glut 4 = muscle, adipose (low km, insulin dependent)
• Glut 5= small intestine (fructose transporter)

• Peptide: acts on a receptor outside the membrane
• Secondart: lipid soluble, so enters cytoplasm or nucleus and therefore can affect gene transcription

epinephrine/norepinephrine, dopamine (Parkinsons)

seretonin (sleep cycle/depression/gut fnx)

Nitric Oxide ---> stimulates guanylate cyclase --> generates cGMP (second messenger)-vasodilator

insulin + tyrosine receptor --> phosphorylates insulin receptor subunits (IRS) --> various biological pathways

• steroids/cholesterol: androgens, mineralcorticoids, glucocorticoids
• intracellular regulation

• 1- signal binds to receptor
• 2- receptor changes confirmation
• 3- change activates G protein and its supbunits to bind GTP (active)
• 4- alpha subunit dissociates to activate a target enzyme:
• ----adenylate cyclase: Atp --> cAMP (2nd mess)
• ----phospholipase C: PIP2 --> IP3 + DAG + Ca2+
• 5- alpha subunit binds back to GTP to make it GDP (inactive)

ex: nicotonic choilinergic neuroreceptors (Na+/K+ influx @ neuromuscular Jnx)

• D configuration- OH on Right of highest # C in Fisher
• Alpha- OH points down
• Beta- OH points up

• if the anomeric OH of a ring is not involved in a reaction, it can act as a reducing sugar
• -all monosacharrides
• -all disaccharides (except sucrose!)
• -all polysachharides (but only weakly reducing)

Sucrose --> Glucose + fructose

• -fructose malabsorption --> IBS
• -hereditary fructose intolerance (aldolase B deficiency)

• Lactose --> glucose + galactose
• Lactose intollerance- missing lactase enzyme

• Plants use starch
• --amylopectin (70%)- branched alpha 1,4 and alpha 1,6
• --amylose (30%)- unbranched alpha 1,4

• Animals use glycogen (muscles & liver)
• ---many branches, alpha 1,6

• long chain branched heteropolysaccharide
• highly negative and slippery (shock absorber, synovial fluid, vitreuous humor, umbilical cord)
• -made up of repeated disacharide units

• E1- PDH (thyamine pyrophosphate TPP)
• E2- Dihydrolipoyl Transacytlase (lipoic acid & co-A)
• E3- Dihydrolipoyl Dehydrogenase (FAD & NAD+)

• Pyruvate Dehydrogenase Kinase: adds Pi to E1, deactivatin it
• ---regulatory molecules to turn PDH off: NADH, ATP, acetyl co A

• Pyruvate Dehydrogenase Phosphotase: removes Pi, activating E1
• ---regulatory molecules to turn on PDH: NAD+, ADP, coA, pyruvate, Ca2+

• citrate -- FA synth
• alpha keto glutarate --- glutamine + NT (GABA)
• succinyl co A --- heme synthesis
• malate -- gluconeogenesis
• OAA -- AA synthesis

to convert cytosolic NADH back to NAD+

coupling ETC to ATP synthase

binds to Fo pore portion of ATP synthase , inhibitng ATP synthesis by inhibiting H+ ions to enter the channel

uncouple oxidative phosphorylation (H+ enters matrix without Fo channel of ATP synthase and doesnt produce ATP but rather uses the Energy as Heat)

• chemical uncoupler
• benzene ring 2 2 nitro groups and a dissociable H+
• high [H]+ in intermembrane can add to deprotonated 2,4 DNP
• protonated (uncharrged) form cann mass through membrane into matrix
• H+ released into matrix

• Chemical Uncoupler
• antibiotic that makes the inner membrane permeable to K+
• no proton motive force, but gradient remains

forms a non-specific channel that allows H+ to pass through

• utilize uncoupling proteins to uncouple ETC from ATP synthase
• form H+ channels through inner mito membrane to allow H+ flow
• UCP1= brown adipose (thermogenin)
• UCP2= most cells
• UCP3= skeletal muscles
• UCP4 & 5= brain

TAG > [lipase] > FA + glycerol > [blocks ATP synthase so E cant be produced so instead...] > Heat is produced!

• Outter membrane: use VDACS- non specific pore
• Inner membrane: use adenosine nucleotide translocase (ANT) that allows an antiport ATP:ADP 1:1 exchange

• atractyloside (mold toxin): inhibits transport on the cytosolic side
• bongkreik acid: inhibits transport on matrix side

*both act on adenosine nucleotide translocase (ANT)

• -signaling molecule to activate glycolysis
• -F16BP --> [PFK2] --> F26BP stimulates PFK1 to activate glycolysis

• increase protein phosphorylase
• activates glycogen synthase
• increases glycogen

• Increase protein kinase
• activates glycogen phosphorylase
• increases glucose

• super oxides (o2-)
• hydrogen peroxides (h2o2)
• hydroxyl radical (OH.)

• Nitric Oxide (NO-)
• peroxynitrite (ONOO-)

• Refers to the fact that Oxygen has 2 unpaired e- in 2 different orbitals
• therefore, inorder to react, an atom needs to donate 2 PARALLEL pairs of e- (which is not common...)
• therefore oxygen is known as a "stable" radical

hydrogen peroxide converting to a hydroxyl radical via Cu or Fe transition metal

common in crush injuries where lots of Fe are released

Similar to Fenton Rxn, except requires O2 superoxide to react with H202

H202 + O2 ---> hydroxyl radical

• Cystine
• Arginine
• Methionine
• Proline

CAMP

• due to lipids in the presence of free radicals
• produces peroxyl lipids (LOO.) and lipid peroxides (H2OL)
• degrades to malondialdehyde....toxic and dangerous to DNA

• produced deliberately (ex: in inflammation)
• accidental products of normal reactions
• exogenous: ionizing radiation, UV, toxic chemicals, drugs
• most superoxides come from CoQ of the ETC

• enzyme that adds one atom of O2 to water and the other into the substarte
• ex: Cytochrome P450
• elevated in chronic alcoholics because because ethanol metabolism releases acetyl aldehyde which later releases free radicals
• liver cirrhosis --> fibrosis

• NO- smooth muscle relaxation, NTs
• superoxides- blood pressure, signal transduction, controls ventillation

• I: neurotransmitters (Ca2+)
• II: fight infection (inducible, cytokines or bacterial lipolysaccharides)
• III: vasodilator (ca2+)

• main source of RNOS
• activates NADPH Oxidase Complex
• Neutrophil > produces NO > activates NADPH oxidase > uses O2 to make superoxides to fight infection
• (cataylytic beta subunit transfers e- from NADPH to FAD) defective beta subunit usually leads to Chronic Granulomatous Diseas --> cant fight infection

• synthesis of NT, FA, Steroids, Cholesterol
• detoxification of ROS via reducing glutathione
• Generate respiratory bursts- from attacking ROS
• nitric oxide signaling- vasodilation

• Most cells can produce NADPH in alternative methods besides PPP by using malate dehydrogenaseRBCs cannot, so relies fully on PPP
• deficiency of G6P leads to heinz bodies- denatured proteins in RBC that due to lack of NADPH
• breakdown of RBCs leads to anemia and jaundice

Malarial parasites require reduced glutothione and PPP productss to grow, so without them, they die

dfinition: anything that causes RBC oxidative stressinfection (most common)oxidative drugs = antimalarials, antibiotics, antipyretics fava beans

• AOX defense enzymes
• Endogenous AOX
• Dietary AOX
• Compartmentalization- peroxisomes, metal cofactrs to prevent rnxs
• General repair mechanissms- DNA repair, degrade and resynthesize affected proteins, removal of oxidized lipids

O2. --> H202 (not toxic), releases oxygen that immediately binds to positive factors

• cytosolic and extracellular forms require Cu+ or Zn+
• mitocchondrial form requires Mn+

• H2O2 --> O2 + 2H20
• usually found in liver and kidney because thats where most peroxisomes are

• H2O2 --> H2O
• reduces peroxide into water
• reduces lipids to alcohol
• found in mitochonria and cytosol

• Endogenous Scavenger
• water soluble so enters plasma, saliva, and lungs to scavenge free radicals

• dietary AOX
• contains tocopherols- terminates free radical chain reactions of lipid peroxidation
• alpha isomer acts against ROS
• gama isomer- acts against RNOS

• dietary AOX
• regenerates the reduced form of Vitamin E

gets rid of ROS with its long conjugated double bond structure

• denatured in the stomach and absorbed by intestinal mucus cells
• purines converted to uric acid and excreted in urine
• pyrimadines go back into blood stream

• lipoproteins that resynthesize TAGs, cholesterol, etc and released them back into the blood
• excrete as a vesicle from the Golgi and then enter lymphatic circulation
• ApoE- hepatic receptors that recognize chylomicrons
• ApoCII- activates lipoprotein lipase (normally found on surface of capillaries)

• conjugated via glycine (75%) and taurine (25%)
• conjugation allows the formation of hydrophobic/philic sides to permit lipid digestion
• primary bile salt: synthesized by liver (recycled)
• secondary bile salt: synthesized by gut flora (excreted)

"CADET Right!"

• Shift to the Right, low affinit for O2 due to increase in:
• +CO2
• +ATP
• +23BPG
• +Exercise
• +Temp