Diseases Complete

8/12/2019 Diseases Complete

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Ehlers-Danlos

Syndromes

Collagen III

ELASTINE

lysine hydroxylase

gene

Skin doesnt have

tensile strength

Hypertensible

hypermobile joints

varicose veins,

Arthritis

Menkes Disease Collagen Copper-

transportinATPase gene

ATP7A

Lysyl oxidase Hypotonia

Depigmented (steely)hair, Cerebral

degeneration

Osteoporosis

X-linked

Ressesive

S

curvy

Collagen Vitamin C Deficiency

Rebound scurvy:

immediate halt to

excess vitamin C

supplements

Petechiae, ecchymoses,

loose teeth, bleeding

gums, poor wound

healing.

Petchiae are

minute bleeds

because

collagen isnt

there to hold inplace. People at

risk: infants,

elderly men,

alcoholics,

smokers. Will

occur after 20-

40 days.

MarfansSyndrome

ElastinMicrofibrils!

Mutation in genefor Fibrillin-1

(FBN1)

Fibrillin-1 is a keycomponent for

connective tissue&

organizes Microfibrils -

composed of elastin&

fibrillin

SHE AutosomalDominant

disorder. Cant

see because of

elastic fibers

attached to

eyes.


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Charcot-Marie-

Tooth Disease

Marie dice para

comprar enGap?

Mutation of Cx32

GAP junctions

Caused by an inherited

connexin protein

mutation (Cx32) on X

chromosome

Degeneration of

peripheral nerves, slow

loss of muscle control,

muscle degeneration

Inherited, most

common

Cholera Toxin

(40)

Gs Signaling Chemically

modifies Gs so

subunit can no

longer hydrolyze

GTP

Gs signaling will stay

on! CFTR; High cAMP

levels

Severe diarrhea & water

loss.

WhoopingCough (Pertussis

Toxin) 43

Gi Signaling Inhibits Gi higher than normallevels of cAMP

Malignant

Hyperthermia

Ca+ Ryanoidine

Receptor 1

anesthetics&

depolarizing muscle

relaxans

sustained muscle

contraction, attendant

hypercatabolism

Achondroplasia Tyrosine

Kinase GF

Receptor

Mutation in

Fibroblast Growth

Factor Receptor 3(FGFR3)gene

This gene is the

hottest spot for

spontaneous mutationinfather

Short-limbed dwarfism,

small stature, large head,

prominent forehead,lumbar lordosis

Type 1 Diabetes

(Insulin-

Dependent)

Tyrosine

Kinase

Islet cells in pan

creas

Autoimmune

destruction of islet

cells in pancreas

Occurs in children,

Ketoacidosisindicative

of body not using glucose

alternative sources,

polydipsia.

Autoimmune

Disorder where

you cannot

produce insulin

properly.

Common in

NAW


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Type 2 Diabetes Tyrosine

Kinase

Signal

Transduction

Insulin resistance Multifactoral; End renal

stage disease, vascular

disease, retinopathy. NO

ketoasidosis,

Athersclerosis

Problem with

cells responding

to insulin

because signal

transductionisnt being

turned on

Tuberous

Sclerosis

Tyrosine

Kinase

TSC1 or TSC2

Mutation

2/3 of cases are due to

spontaneous mutation

Multiple Facial

angiofibromas,

hypopigmented macules,

seizures

Inherited

disorder

Hutchinson-

Gilford Progeria

Nuclear

LaminDisease

Mutated LMNA

gene

LMNA encodes for

lamin A- chromatin)

Premature aging and

death. Abnormal growth,scleroderma-like skin

There are

several forms ofProgeria

Fragile X Microsatellite

DNA DIsease

Too many CGG

repeats (exceed

200)

Triggers

hypermethylation of

the FMR1gene

heterochromatin

NOT

EXPRESSED/TURNED

OFFshutting downtranscription

Mental retardation.

Anticipation: worse if

mother passes it on!

Macroorchidismlarge

testis. Autistic-like

behavior.

X Linked. Most

common single

gene mutation-

mild mental

retardation


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Turners

Syndrome

Trisomy (3n) Results from

fertilization by 2

sperm or from

failure of one of

the meioticdivisions

Should be suspected in

any newborn female

with edema of

hands/feet or

hypoplastic left-sidedheart/coarctation of

aorta. Also considered

in teenager w/

amenorrhea (short

stature)

Short stature, webbed

neck, renal &

cardiovascular

abnormalities. AT BIRTH

infants have edema ofdorsum of foot.

Lymphedema in fetal life.

Average+ intelligence.

Worse cognitive if X from

mother

Most common

karyotype

found in

spontaneously

aborted fetuses


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Drug Cellular Component Function Clinical Setting Notes

Taxol Microtubule assembly Stabilizes MTs Breast Cancer Therapy

Cholchicine,vinblastine,

vincristine, and

nocodazol

Microtubule Growth Inhibit MT growth, mitoticinhibitor. Binds subunits &

prevents their

polymerization

Used to treat cancer

Penicillin Inhibits the enzymes

DD-trasnpeptidase

(bacterial cell wall

crosslinking)

Prevents cell wall synthesis

and bacterial growth. DD

usually form the cross-links

of cell wall

Many bacteria are now

PCN resistant

Nitroglycerin NO & smooth muscle Glycerol trinitratedecomposes to NO which

relaxes arterial smooth

muscles

Chest pain due toconstricted vessels.

This will vasodilate

Viagra Inhibitor of cGMP-

specific

phosphodiesterase

Wont break down cGMP

and cause PKG active &

muscle relaxation &

vasodilation

Erectile Disfunction

needs vasodiliation

which is a cGMP

process

Methylxanthines Primary: antagonist ofandenosine receptors

Secondary: inhibition

of cAMP

phosphdiesterase

Prevent cAMP breakdown Caffeine fromcoffee/tea

Theophylline from tea

Theobromine fro

chocolate

Cyclosporin A Inhibits Calcineurin Immunosupressant. Works

to inhibit calcineurin so

NFAT will not be

dephosphorylated and IL-2

Organ Transplant

Patients


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expression is decreased!

Cytochalasin B Disrupt MF & Inhibit

movement & cell

division

Bind to barbed ends & block

elongation.

Quinolones/fluoroquinolones

Inhibit DNA gyrase Prevent DNA

replication/transcription

Synthetic antimicrobial

agents, highly effective

in treating infectious

diseases

Nalidixic acid,

Ciprofloxacin,

Noorfloxacin

Rapamycin Immunosupressant Recently discovered to

prolong life in mice

Zidovudine Polimerase DNA

inhibitor

NSAIDS- inhibit cox 1

Ibuprofen- arthritis

Cox I- housekeeping

Cox II induce by special cells

Digoxin- increase contraction in cardiac, when block Na/K

Oubin- Inhibit Na/K pump (SWELLING CELL)


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Glut I- RBC

- Maintain g6p into de cell when is tag with hexoquinaseif I removed this the g6p loss a fosphate and going to the cell..

Glut II- bidireccional glucose transporter in the liver

Glut III- neuronas

Glut IV- diabetes II

Glut V- Fructose


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Disease Types of Disorder Gene Affected CellularComponent

Symptoms Notes

Xeroderma

Pigmentosum

NER XP causes extreme

sensitivity to UVradiation & Multiple

skin cancers

XPA

XPG

UV light = thymine

dimmers; cant be fixedin XP

Sun sensitivity, ocular

involvement, greater than1000x risk of cutaneous &

ocular neoplasms.

Recognized early. Dry skin

(xerosis) and Poikiloderma,

Atrophy of the skin

Marked freckling of face

of child under 2 istypical of XP

Cockaynes Syndrome TCR Mutated CSA & CSB

genes

Defect can lead to the

wrong protein

expression

Growth failure, impaired

nervous sensitivity,

premature aging, increased

sensitivity to sunlight

HereditaryNonpolyposis Colon

Cancer (HNPCC)

MR Mutations in MLH1 &MSH2 (genes coding

for proteins involved

in mismatch)

MLH1 and HSH2 arehuman homologs of

MutL an MutS

Increased risk of Colorectalcancers and GI tract &

urogential tract cancers

1 of the most commoninherited diseases;

Autosomal Dominant

Hereditary Breast &

Ovarian Cancer

HR Abnormal BRCA1 and

BRCA2 genes

BRCA1confers high

risk of breast & ovarian

cancer

BRCA2breast and

prostate

Systemic Lupus

Erthematosus

Splicing Anti-Sm & Anti-RNP

specifically recognizesplicing SnRNPs.

Autoantibodies

Chronic systemic

autoimmune disease &loss of self-tolerance

Inflammation of membranes

around lungs/heart,arthritis, butterfly rash,

photosensitivity, seizures,

renal problems, recurrent

infections


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Beta Thalessemia Splicing Beta Globin is

mutatednot

making enough HbA

B chain synthesis is

decreased or absent.

Excess Globin Inclusion

Bodies

Severe hypochromic

microcytic anemia during 1st

year of lifestimulation of

erythropesismarked

expansion of marrow space

Characteristic skeletalchanges. Enlarged

liver/spleen

Upregulation of HbF and

HbA2 because there

isnt enough HbA. Most

common disorder of

pakastinian descent

Blood transfusion

treatment

Sickle Cell Anemia MM Mutation in the 6th

codon of globin

gene. From

GlutmateValine

Mutation causes HbS

hemoglobin to

polymerize (stick)

under deoxygenated

conditions. this causes

an inflexible RBC

Jaudice in eyes; Severe

hemolytic condition (1st

2

years), anemia, failure to

thrive, splenomegaly,

painful swelling of

hands/feet, repeated

infection

African Descent ;

autosomal recessive

Diphtheria Toxin &Pseudomonas Exotoxin

(A)

TI Target EF2 & inhibitelongation

Chemical modify thetranslocation step; they

do this by ADP-

ribosylation

Li-Fraumeni Syndrome Transcription Factor

Decect

Mutant for of the

TP53gene (codes for

p53)

Mutations in both allels

are necessary to

inactivate the TP53

gene

Rare Cancer Families with

a history of different forms

of cance. Affected at an

early age (relativiely)

Inherited in an inherited

in an autosomal

dominant pattern

Ataxia- Telangiectasia Imunodeficiency; DNA

damage

Inherited mutation in

the gene encoding

ATM

Predisposition to

Cancer. Cells do not

stop and apoptosis.ATM regulates DNA

comprosmise of

signaling pathways

Progressive, degenerative

disaeas that affects a variety

of blody systems. Normal atbirthsysmptoms present

at 2 year of life. Pron to

development respiratory

infections . Tiny red spidery

veins

Prader-Willi Syndrome Genomic Imprinting Abnormal

chromosome 15

Inherited from father Obesity, excessive &

indiscriminate eating

habbits, small hands & feet,

short stature,

hypogonadism, MR


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Angelman Sydrome Genomic Imprinting Abnormal

chromosome 15

Inherited from mother Unusual facial appearance,

short stature, severe MR,

spasticity & seizures

Autoimmune

Lymphoproliferative

Syndrome

Apoptosis Mutation in Fas

Ligand or Fas

receptor

Drug Cellular Component Function Clinical Setting Notes

Rifampin Interfere w/ transcription Inhibits initiation of RNA synthesis in

bacteria by interfering with the formation

of the 1st

few phosphodiester bonds in the

RNA chain

Used to treat TB Derived from strain of

Streptomyces

Actinomycin Interfere w/ transcription Binds tightly to double stranded DNA

preventing it from being an effective

template for RNA synthesis.

Used infrequently in treatment of

malignant neoplasmsWilms

Tumor sarcomas

Used in both prokaryotes

Aminoglycoside

(Streptomycin)

Interfere w/ Translation Bind directly to the 30S subunitprevent

initiation of translation. Induce misreading

if translation does occur

Antibiotics

Tetracyclines Interfere w/ translation Bind to 30Sphysically prevent

aminoacyl tRNA from getting into A site

(acceptor)

Antibiotics Doxycycline, Minocycline,

Chlortetracycline

Chloramphenicol Interfere w/ translation Binds to 50S subunitinhibits the

peptidyl transferase activity of 23S rRNA

Antibiotics Seleciviely interferes with

23S

Puromycin Interfere w/ translation Mimics the shape of aminoacyl-tRNA

becomes incorporated into growin peptide

chain = inhibit elongation

Antibiotics

Macrolides &

Clindamycin

[Erythromycin]

Interfere w/ translation Bind to 50S subunitprevent

translocation during protein synthesis

Antibiotics Erythromycin,

Roxithromycin,

Clarithromycin

Bortezomib Proteasome Inhibitor Binds the catalytic site of the 26S

proteasomeinhibition prevents

degradation of pro-apoptotic factors.

Treatment of multiple myeloma,

decrease growth of cancer cells


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Permitting activation of programmed cell

death. Activation of apoptosis

Warfarin Interfere w/ post-

translatoinal modification

Interrupts carboxylation in post-

translational modification of proteins. Vit-

K dependent carboxylation is important in

acivty of blood-clotting factors.

Anticoagulant (blood thinner)

used to treat blood clots

Often used after surgery

to prevent clots in

healing; given to MI

patients

Technique Method Goal Key Reagent/Probe

Reporter Gene Transfer Assay Plasmid constructluciferase

directs expression on reporter gene

in cultured cells

DNA-Protein interactions; Analyze

point mutations

Luciferase (cloned from fireflies). Wild

type shows 1000x while mutant has

50x how is this explained?

Purification of TF by DNA-affinity

chromatography

Purify transcription factor SP1binds to GC box


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Retinoblastoma Tumor Suppressor

Mutation

Mutated Rb Gene

(Tumor Supressor

Gene)

Rb regulates the G1Sphase. Rapid rate of

proliferation

Tumors in the eyes;

white reflex

Dominant Trait;

removal of eye. 2ndhit

is matter of chance.

60% sporaticFamilial Breast Cancer BRCA1 & BRCA2 BRCA1: Chrom 17q21

BRCA2: Crhom 13q12.3

Familial Polyposis Coli Tumor Suppressor

Mutation.

Mutation of APC

(Wnt signaling

pathway)

ACPencodes a cytoplasmic

protein that regulates b-

catenin. Loss of APC leads to

accumulation of free regulates

b-catinin thats translocated to

the nucleus & activates

transcriptionElevated b-

catining and cell proliferates

Polyps in colon before

25. Numerous benign

growth (polyps) usually

one or more polyps

become malignant

Colectomy prevents

development of

malignancies

Hepatocellular

Carcinoma

Carcinogen Ingestion Aflatoxin B1

produced by mold

found on peanuts

Modifies base in TP53 causing

GT in codon 249. Arginine

Serine in p53 protein.

Arg249Ser enhances

hepatocyte growth &

interferes w/ apoptosis

Aflatoxin B1 acts

synergistically w/

chronic hep B & C

Found in parts of world

w/ high food

contamination by

aflatoxin

Follicular B-cell

Lymphoma

Chromosomal

Translocation

(Oncogenes)

Upregulation of

BCL2

Done by translocation which

brings immunoglobin

promoter & enhancer in

proximity to BCL2Acute Promyelocytic

Leukemia

Chromosomal

Translocation

(Oncogenes)

PML/RARa fusion;

interferes w/

normal homologs

blocks cells diff

& keeps leukemia

in active

proliferation state

Mutated forms of retinoic acid

receptor act as oncogene.

T(15;17)(q22;q12)chimeric

protein that arrests

maturation of myeloid cells at

promyelocytic stage

increase proliferation of

promyelocytes

Accumulation of

promyelocytes in bone

marrowRBC &

platelets = anemia &

thrombocytopenia

Can be treated by

retinoic acidinduces

differentiation & blocks

continued cell

proliferaiton

Burkitt Lymphoma

(Non-Hodgkins)

Chromosomal

Translocation

(Oncogenes)

MYC gene is under

influence of

enhancer from

Associated w/ EBV. MYC chom

814

Solid tumor is composed

of aberrant B-cells

Common tumor of

children in equatorial

Africa. MYCfunctions as


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Diseases Complete