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8/6/2019 Explain Low Energy State
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Explain Low Energy State (LES)The body is in the business of staying alive,
when anything interferes with the system,the body begins to dies. The parts of the
body that dies first are the mitotically active(or rapidly dividing) cells.
Symptoms LES? Brain - Confusion
Muscle - WeaknessLung (Cilia) -
Kidney (PCT) -Skin - Dry and Cracked
Hair - BrittleCuticles
GI Tract - N/V Bone Marrow - Suppressed Endometrium -
Atrophic
Sperm count - Low Bladder - Hemorrhagic CystitisVascular - Vasculitis
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MC:SSx/Infx/CODfor LES Sign Dyspnea/Tachypnea
Symptom Weakness/SOBInfx Pulmonary/UTI
COD - Heart Failure
Only "Imino" acid? Proline
Common with all Amino Acids? They all have:
Amino & Acid group
Define: Dissociate, SolubleBioavailable
Dissociation - Giving up H+Soluble - Charged Bioavailable -
Uncharged
Best AA buffer in bodiesHistidine
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Define Anode and Cathode Anode - Pole anions go to
Cathode - Pole cations go
What is the pH in the GI Stomach 1-2Duodenum 3-5
Early Jejunum 5-7 Late Jejunum 7-9
Ileum >9
Define isoelectric point. Isoelectric Point means there is "No Net Charge"
What does Ketogenic mean? Made from and broken into AcCoA (Avoid in
DM)
What does Glucogenic mean?
Made from and broken into Anything but AcCoA.
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For each of the following, give the Amino/Imino acid:
Smallest - GlycineKinks - Proline
Basic - Lys, Arginine Acidic - Glu, Asp
N-Bonds - Asn(99%), GlnO-Bonds - Ser, THr, Tyr
Sulfur Cys, Met Aromatic - Phe, THr, Try
Branched Chains LIV Ketogenic - Lys, Leu
Both PITT
Essential PVT TIM HALL
Which amino acid is used to make cystein? Methionine
Four hormones with disulfide bonds.ProlactinInsulinInhibin
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Growth Hormone
Newborn Screening diseasePKU CAH
BiotinidaseGrown HormoneHypothyroidism
GalactosemiaSickle Cell
Enzyme deficiency in PKU Phenylalanine hydroxylase
S/Sx of PKU Musky odor
MRFair Skin
Blue EyesBlonde Hair
AA deficient in PKU
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Tyrosine
What Substances build up? Phenyl-PyruvatePhenyl-Acetate
Treatment for PKU Avoid Aspartame
What Product has Aspartame? Nutriasweet
Defect in MSUDNephron Transport Protein
S/Sx of MSUDSweet Urine
AA s in MSUD
LeucineIsoleucineValine
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Defect in Cystein UreaCystine
OrnathineLysine
Arginine
What crystal are seen in Cystein UreaCoffin lid/Envelope shaped
Amino Acids humans have? L-Amino Acids
What determines AA Primary Structure?
Amino Acid Sequence
What is the primary factor to determineStructure of Protein?
Hydrophobic-Hydrophilic interaction
What are 3 characteristics of peptide bonds? Planar - Flat
Limited Rotation
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Trans ConfigurationWhat is characteristic of amino acid
quaternary structures? Allesterism (Cooperatively)
For Enzymes, Define KM, Vmax.Km - Potency
Vmax - Efficacy Km = Vmax
Km = 1/Affinity
How does noncompetitive INH work? Binds to active site.
Km increases.Vmax stay the same
How does noncompetitive INH work? Binds to Regulatory Site and Inactivates the
proteinKm stays the same.Vmax decreases.
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Metabolized in Zero and first order substances
Constant Amount Constant percentage
Three 0 order substancesPhenytoin
EtoH ASA
0 order number for EtoH 100mg% or 100 [mg/dl]/hr)
Define GABA connection? NH4 + aKG Glu GABA Slows things
down
From what are porphorin rings made?
Succinyl -CoARate Limiting enzyme in Heme Syntehsis?
Delta - Amiolevulonic Acid Synthase(D-ala)
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What are the structures of Hb A, A2, and F?
A - a2b2 A2 - a2d2
F - a2g2
In what percentage does each exist in thebody?
A - 98% A2 - < 2% in
F child < 6 mos.Enzymes INH by Lead in Heme Systhesis
d-ALA/ Ferrochetalase
What Enzyme adds Iron to porhorin rings? Ferrochetalase
What buffers in Fe2+?
HISTIDINE # of heme sites in 1g heme
Four
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Grams of iron in 1U blood
3.4
Acute Intermittent PorphoriaRecurrent, Severe, Acute abdominal pain &
Neuropathies
Clues for Porphoria Cutanea tardaBlisters with light
Onset > 5 yr
Clues for Erythrocytic protoporphoria
Blisters with light Onset < 5 yrs
Rx for AIP Fluids, Sugar, Hematin
MCC Aggravation of AIP Stress and Menses
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Define Hemosiderosis and HemochromatosisHemosiderosis - Iron load Overwhelm BM
Hemochromatosis - Iron Deposition inOrgans
What causes Primary Hemochromatosis? Duodenum is absorbing too much iron
ARHLA A3
What causes secondary Hemochromatosis? Too many blood Transfusion
Timeline for erythropoiesisStarts 4 mos. - Yolk Sac
6 mos - liver/Spleen/Flat B8 mos - Long Bones
1yr - (-) Liver/Spleen/Flat B
Wipe BM - Spleen opens upWhat is the defect in all the thalassemias? Gene Deletion
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# genes for Alpha/Beta Alpha 4
Beta 2
Define thalassemia minor/major.Minor 1 gene left Major No genes
Alpha Minor 1 gene Asymptomatic
Alpha Minor 2 genes
Active - SymptomaticNot Active - Asymptomatic
Hb Bart Beta Tetramer
Alpha Minor 3 genes
Symptomatic Alpha Major 4 genes
Hydrops Fealis
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Beta Minor
(+/-) SxS OK until 4-6 months
Beta Thalassenia Major Always SymptomaticTransfused dependant
Only Hg A2 and F Cooleys s Anemia
What is Cooley s Anemia? Big Skull, Hepatoplenomegaly
Big SternumBig Pelvis
What will the COD for Beta-Major? 1st 10 yrs Infections
Teens Hemochromotosis Acids used in medicine? Mb, Phenobarbital,
ASA,TCAs
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Base used in Medicine
Base - NaHCO3
Bases Used in Medicine Amphetamines
Acid used for treatment in Hospital NH4Cl
(9) causes of Right Shift of Oxy-Hb curve? Hypoxia
Increased Lactic Acid
Increased 2,3 DPGIncreased [H]
Increased TempIncreased AltitudeIncreased Exercise
Decreased pH Increased PCO2
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Released from muscle cells duringRhabdomyolysis?
Myoglobin
Fetal circulation:100% - From Placenta
80% - Umbilical Vein + blood from feet viaDuctus Venosum
60% - Inferior Vena Cava50-53% - Right Atria
80% goes Foremen Ovale Left Atria
20% goes Right Ventricle Pulmonary
Artery 20% - Lower Extremities Umbilical
Arteries Placenta
Carbon Monoxide
Competitive Inhibitor Binds 200x stronger than O2SaO2 is HighPO2 is Low
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Rx for CO2 poisoning?
Hyperbaric O2
CyanideNon competitive Inhibitor
PO2 is normal SaO2 is Low
MCC Cause of CN poisoning? Sodium Nitroprusside used for Hypertensive
Crisis
Rx for CN poisoning? Amylnitrate - Fe2+ Fe3+
Thiosulfate ThiocyanateMethylele Blue Fe3 Fe2
Rx methemoglobinemiaMethylene Blue
What causes primary methemoglobinemia?
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Congenital
What causes Secondary Methemoglobinemia?
Drugs MC sulfa
What is the PO2 and SaO2 for methemoglobinemea?
PO2 is Normal SaO2 is Low
Effect of acid hydrolases on proteins? Denatures Protein
Change ASN ASP Change Glutamate to
Aspartic acid and glutamic acid
How does GEL electrophoresis work? Separates by size
Separates by charge
How does the Ninhydrin reaction work? Turns AA purpleTurns Proline Yellow
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How does the Edmon's degeneration work? Uses Phenyl/Iso Thiocyanate
1 AA at a time from Amino Only good for 100 AA.
Trypsin Cuts to right of Lysine, Arginine
Chymotrypsin Cuts Phenylalanine,Threonine, Tyrptophan
Elastase Cuts(Hlycine, Alanine, Serine)
CyanatobromideCuts(Methinonine)
Aminopeptidase Cuts
(Amino Terminal)Carboxypeptidase Cuts
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(Carboxy Terminal) Only that cuts to theleft.
Mercaptoethanol (Dissolves disulfide bonds)
4 most abundant collagen
I - S - Skin and BoneII -C - Connective Tissue
III -A - ArteriesIV -B - Basement Membrane
What protein in defective in Marfans? Fibrin Protein
Clues for MarfanWingspan > height Arachondactyly
Lens disloc from bottom
Clues for Ehrlers-Danlos? Hyperstretchable Skin
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How does Homocystein work? INH lysine hydroxylase INH collagen
synthesis
Clues for HomocysteinureaDislocate lens from top
What is the defect in scurvy? Vit C is needed to hydroxylate Lsy and Pro in
Collagen Synthesis
Clues for Scurcy Gingival Bleeding
Perfolicular Hemorrhage
Clues for SyphilisObliterative Endarteritis
Tree barking
Shooting, Lancinating PainClues for Congenital Syphilis
Anterior bowing of legs
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SnufflesHuthinson's teeth
Defect in Minky's Kinky Hair disease? Cu2+ deficiency
Clues for Minky's Kinky Hair looks like copper
Hair cuts face
Name the diseaseDilocation from Top
Dislocation from botton
Perifolicular hemorrhageBlue Sclera
Copper looking hair Tree barking of aortaHyper-stretchabls skin
Pulseless AortitisDifferentiate OI from abuse
OI Shattering fracture
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In what population do you see Takayasu
disease?
Asian Women
What is Takayasu? Granulomatous Aortitis
What is the only protein modified in the ER? Collagen
What are the Amino acids found in collagen?
Gly, Pro, Lys
What vit is needed for collagen synthesis? Vitamin C
What other mineral is required for collagen? Copper
What two A.As are Hydroxylated in Colagen?
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Proline and Lysine
How do all proteins begin? Pre-Pro-Protein
In what form is collagen secreted? What happens after secretion?
Collagen is secreted from the GOLGI asTropocollagen and a cytoplasmic Peptidase
Cleaves off OH To what structure does each of the following
guide a protein?
Where do each of the following guide a protein? Pre- ER
Pro - GolgiMan-6-Phos - Lysosomes
Short Amino Terminus Sequence mitochondria
Diff bt. elastin & collagen?
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Elastin has no OH-Lysine.
What gives Elastin elasticity? Desmosine (4) Lysines
Enzyme breaks down Elastin? Elastase
2 bacteria with elastase? Staph , Psuedomonas
How does the body INH elastase?
With antitrypsin
Define Emphysema? Cystic Dilation of the alveoli
4 types of emphysemaPan-acinar Antitryp def Centri-acinar - Smoking
Disto-acinar - Age
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Boullous Staph/Pseudo
Another name for boullous Pneumatocele
What providesTensile strength? Keratin
Kinds of bonds in KeratinDisulfide bonds
5 Actions of EnzymesBring [S] together
Stabilizes HEI
Lower free EOANot consumed
Reaction goes faster
ETC complex needing Fe?
Cpmplex III and IV ETC complex needingCu?
Complex III
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FADH2/NADH feed ETC at
FADH2 Complex II NADH Complex I
InhibitingETC means? Stop electron transport &
Stop Heat generation.
Uncoupling ETC means? Stop electron transport, but Heat generation continues
ETC InhibitorsI - Amytal, Rotonone
II - MalonateIII - Actinomycin D
IV - CN , CO, Chloramphenical
V - OligomycinETC Uncouplers
DNP - Dinitrophenol
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ASA - AspirinFFA
Who has uncoupled ETC Babies & Polar Bears
Naming enzymes1st name - SubstrateLast name Action
Type of Sugars & AA in humans? L-Sugars
D-Amino Acids
Why does the body phophorylate things? To keep them in the cells
What are the regulatory enzymes in
Glycolosis? Hexokinase, PFK1, Pyruvate KinaseWhere will you find
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Glucokinase is found where? Liver & Pancreas after meal
Hexokinase is found where? Everywhere
List 6 stress hormonesEpinepherine - Immediately
Glucagon - 20 minutesCortisol - 2-4 hours
GH - 24 hoursInsulin - hour
ADH with Osm
7 not requiring Insulin to Take up Glucose:B - BrainR- RBC
I - Intestinal Wall C - CorneaK - Kidney L - Liver
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E - Exercising Sk. Muscle
3 enzymes needing B1Pyruvate Dehydrogenase
Alpha KG DehydrogenaseBrached chain AA DH
List the B vits and namesB1 - Thiamin
B2 RiboflavinB3 - Niacin
B4 Lipoic Acid
B5 Pantothenic Acid B6 - Pryladoxmine
B9 - FolateB12 - Cyanocobalomine
List Cofactors for B vitsB1 - TPP B4 Lipoic Acid
B5 CoA
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B2 FADB3 NAD
List Deficiency for vits A Vight Blindness
B1 Beri BeriB2 Angular Chielosis
B3 PallagraB4 NoneB5 None
B6 Neuropathy B9 Megaloblastic Anemia
B12 Megaloblastic Anemia with
neuropathy C Scurvy
D Osteomalasia/RicketsE
K Bleeding disorder
Clue for Pellagra DermatitisDiarrheaDementia
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Death
Disease like pellagraHartnup
What are sources of vitsB2 - milk
What breaks down B2Sunlight
What cannot be transported in Hartnup? Tryptophan
5 fates of PyruvateLactic Acid
AlanineOAA
AcCoAEtoH
Enzyes for 5 fates of pyruvate
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Lactate Dehydrogenase Alanine Transferase- ALT
Pyruvate CarboxylasePyruvate DehydrogenaseEthanol Dehydrogenase
What is LDH1? Marker for cardiac damage
What is an LDH Flip? 5 LDH s exist. LDH1 is lowest. With MI LDH
1 is highest
Viral vs- EtoH hepatitisViral 1:1 AST:ALT. Alcoholic > 2:1 AST:ALT.
Explain AST: ALT ratio AST in cyto & mitochondria ALT only in the cytoplasm.Viruses membrane 1:1
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EtoH also Mitochondria > 2:1
Most specific cardiac marker Troponin I
MI MarkersT - 2hr P 2d L 7d
L - 6hr P 12hr L 24 hr L 24hr P 48hr L 72 hr
Drugs causing disulfrm rxnDisulfram and Mitronidazole
INH & Act (PFK1)(+) F 1,6BP, F2,6BP
(-) CitrateINH & Act Pyruvate carboxylase
(+) Acetyl-CoA
(-) GlucoseINH & Act CPS1
(+) N-AcetylGlutamine
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(-) NO
INH & Act Glycogen Alpha 1,4Glucosyltransferase
INH & Act G6PD(+) G6P
(-) Ribose-5-P
INH & Act Acetyl CoA Carboxylase
INH & Act Fatty Acyl Phosphorylase
INH & Act HMG-CoA Synthase
INH & Act HMG-CoA Reductase
INH & Act PRPP Gln Aminotransferase
Mercury Inhibits? G3P Kinase
Floride Inhibits?
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Enolase
Signs of Floride poisoning? Pearly white teeth & bones
6 TCA locations for AA s:Pyruvate
Acetyl-CoA Alpha - Keto-Glutyrate
Succinyl-CoAFumerate
TCA enzyme connected to ETC Succinyl-CoA Dehydrogenase.
2. It is connected at Complex II
Intermediates in GlycolysisGlucose
G6P
F6P F16P BHAP/GA3P
1,3 Bis Phosphogluconate
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3 PG 2 PG
PEP Pyruvate
Enzymes in glycolysisGlucokinase/Hexokinase Glucose-6-P
IsomeraseFructose-6-P Kinase
Aldolase AGA3P Kinase
1,3 Bisphosphoguconate DH 3PG Isomerase
EnolasePyruvate Kinase
4 regulatory enzymes in gluconeogenesis
Pyruvate CarboxylasePEPCK Fructose 1,6 Bisphosphatase Glucose-6
Phosphatase
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Intermediates in TCACindy Is Kinky So She Fornicates More Often.
Acetyl-CoACitrate
Isocitrate Alpha-Keto-Gluterate
Succinyl-CoASuccinateFumerate
MalateOxaloacetate
Intermediates in Urea Cycle
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OJ (Ornathine) took the CAR to the City to get some Asp he argued and Fumed, argued
and Fumed and was left alone.
NH4 + CO2 + ATP Carbamoyl-P+ Ornithine
Citruline +Asp Arginosuccinate -Fumerate
L-Arginine -FumerareOrnathine + Urea
Intermediates in Pentose Pathway Glucose Glucose-6-P 6-
Phosphogluconate Ribose-5-P
Intermediates in the Fructose catabolismFructose Fructose-1-P BHAP/Glycerol
Deficiency in FructosureaFructokinase
Deficiency in Fructosemia
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Aldolase B
Deficiency in GalactosureaGalactokinase
Deficiency in GalactosemeaGalactose-1-Urudyl- Transferase
Complications of Fructosurea/GalactosureaPolydipsiaPolyurea
UTI
MCC of UTIs? E. Coli
ProteusKlebsiella
CandidaCarriers in body
UDP Single Sugar
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Dolichol Many SugarsBiotin CO2
THF - CH3 for NucleotideSAM CH3 for everything
CDP - AA
Excess sugarsGlu Sorbitol
Fructose Fructicol Galactose Galacticol