Exam 1: Disease/Disorders Flashcards
1
Q
MSUD (maple syrup urine disease)
A
- deficiency in branched chain alpha keto acid dehydrogenase activity (AD)
- BCAA pathway (Val/ile/leu)
- BCAA in urine smell like burnt maple syrup
2
Q
Homocysteineuria
A
- defective enzyme cystathione beta-synthase OR vit B6(PLP)/12/folate deficiency
- Met a.a. Pathway affected Met–>succccinyl CoA
3
Q
PKU (phenylketonuria)
A
- defect in phenylalanine hydroxylase activity
- Phe–>Tyr–>fumarate pathway
- most common IEM
- disrupt NT=brain impairment
- musty odor to urine
- melanin synthesis impaired (b/c Tyr)
4
Q
Gallstones
A
- bile with too much cholesterol and too little bile salts
- cholesterol hardens to form gallstones
- treatment: oral chenodeoxycholic acid to supplement bile pool
5
Q
Ulcers/indigestion/heart burn
A
- gastric proton pump (H+/K+ ATPase)
- parietal cells pump HCL to make gastric acid in stomach
- treatment: proton pump inhibitor (omeprazole)
6
Q
Fanconi-Bickel Syndrome
A
- mutation in GLUT2
- defect uptake of sugar
- hyperglycemia post meal
- hypoglycemia between meals
- stunted growth
- hepatomegaly accumulation glycogen in liver (cannot leave as free glucose)
- defective insulin secretion from pancreatic beta cells (cannot sense glucose)
- treatment: small/frequent meals and Vit D
7
Q
Cystic fibrosis (CF)
A
- mutation in CF transmembrane conductance regulator gene
- unfolded protein (gets degraded)
- CFTR= Cl- channel, active transport of Cl- out of cell
- build up of Cl- inside cell, salt build up (water follows)
- decreased water surface mucous layer=thick/sticky mucus secretions
- damage to lungs and digestive system
8
Q
Niemann-Pick disease
A
- deficiency in activity of acid spingomyelinase (A-SMase)
- lysosomal enzyme
- least severe form caused by defect in cholesterol transport
- Sphingomyelin accumulates in lysosomes of liver, spleen, CNA, bone marrow
- hepatosplenomegaly
- neurologic damage (retardation, seizures, ataxia)
9
Q
Erythroblastocic Fetalis
A
- mother fetus blood group incompatibility
- Rh- mom and Rh+ fetus
- mom produces Ab’s cross placenta and attack fetus
10
Q
Spur Cell Anemia
A
- elevated cholesterol in RBC membrane
- type of hemolytic anemia
- decreased flexibility/fluidity
- RBC membrane break as pass through capillaries
- beta lipoproteinemia
- associated with advanced stages of alcoholic cirrhosis
11
Q
Hemolytic Anemia
A
- associated with overproduction of ADA in purine catabolism (depleated adenosine–>premature RBC destruction)
- associated with deficiencies in glycolytic enzymes (ex:G6PD)–> decrease energy stores of RBC–>lack of ATP leads to aberrant function of ATPase ion pumps–> accumulation of Na+–> swelling/hemolysis of RBC
- altered G6PD inhibited by low NADPH leads to low reduced glutathione in RBC
12
Q
Cystinuria
A
- defect a.a. Transporter for uptake of Cys, Arg, Lys, ornithine
- AR
- formation of Cys crystals/stones in kidney
- positive nitroprusside test
- renal cholic (abdominal pain in waves)
13
Q
Hartnup Disease
A
- defect transporter for NON-polar/neutral a.a. (Ex: W)
- infancy failure to thrive
- nystagmus
- ataxia/tremor
- photosensativity
14
Q
CHF Drugs (ouabain and digoxin)
A
- inhibit Na+/K+ ATPase on cardiac myocytes
- leads to increase IC Na+
- secondarily increase IC Ca2+ due to slowing of NCX
- increased Ca2+= stronger excitation contraction of heart muscle with each AP
15
Q
Inclusion Cell Disease
A
- defective enzyme that adds Mannose-6-phosphate (M6P) to lysosomal enzymes
- won’t get breakdown of organelle in lysosome b/c missing enzymes and is NOT functional
16
Q
Familial Hyperlipidemia HLP
A
- mechanism of cholesterol uptake is disrupted (defective LDL R)
- elevation of LDL in plasma, leads to atherosclerotic plaques
- R incapable of binding, reduced capacity for binding, incapable of internalizing LDL
17
Q
Zellweger Spectrum Disorders
A
- defects in assemble of Peroxisomes
- most serious case=absence/reduced number of Peroxisomes in cells
- congenital= no cure and death within 1 year of life
18
Q
Cancer drugs (methotrexate= antineoplastic)
A
- inhibit dihydrofolate reductase enzyme
- stops activation of folic acid—>THF
- no THF= no ring closure in nucleotide synthesis in rapidly dividing cancer cells= disruption in DNA replication
19
Q
Orotic Aciduria
A
- hereditary disorder
- target enzyme UMP synthase in Pyrmadine synthesis
- disorder of pyrmadine synthesis treated with oral uridine
20
Q
Immunosuppressant drugs (mycophenolic acid)
A
- target IMP dehydrogenase in purine synthesis
- IMP dehydrogenase converts IMP–>XMP and this is inhibited to prevent graft rejection
- disrupt GMP synthesis and prevent dGTP
- disrupt DNA replication in B and T cells
- Anticancer, Antiviral, Antimicrobial
21
Q
Sulfa Drugs
A
- competative inhibitor of BACTERIAL enzyme that incorporates p-aminobenzoic acid (PABA) into folate
- antibacterial disrupts DNA replication in bacteria
22
Q
SCID
A
- underproduction of ADA (adenosine Deaminase) in purine catabolism
- B and T cells defective
- affect protein needed by R for IL in development of B and T cells
- X-linked (Males only)
- higher amounts of adenosine= high dATP= block synthesis of other nucleotides= impaired DNA synthesis
23
Q
Gout and Gout drugs (allopurinol)
A
- defect in HGPRT (salvage)= excess uric acid
- drug targets xanthine oxidase to form more soluble hypoxanthine
- urate levels>9mg/dL increase risk gout
- painful/inflamed joints
- high levels uric acid in blood (overproduction=primary, under-excretion=secondary)
- sodium urate crystals
- phagocytes engulf crystals and get inflammation
24
Q
Lesch-Nyhan syndrome
A
- defect in HGPRT in purine salvage pathway
- overproduction of uric acid
- hyperuricemia/hyperuricosuria
- gout
- urate kidney stones
- problem with muscle control, retardation
- *excess purines responsible for mental retardation and self mutilation behavior**
25
Acyclovir
- antiviral (heal sores caused by virus)
- cyclic nucleoside analog of guanine
- phosphorylation by VIRAL thymidine kinase converts to acycloMP analog-->acycloGTP-->incorporates into viral DNA--> potent inhibitor of viral DNA polymerase-->termination of viral DNA replication
26
GSD 0
- deficiency in GS
- cannot synthesize glycogen
- muscle cramps due to lack of glycogen in muscle
- rely on glucose in diet (eat frequently)
- vulnerable to hypoglycemia when fasting
27
GSD IV/Andersons Disease
- deficiency in Glucosyl (4:6) transferase aka branching enzyme
- patient have long chain glycogen with few branches
- enlargment of liver/spleen b/c GP not releasing glucose b/c not accesible
- death by 5 years
