Explain Low Energy State

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

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Explain Low Energy State