Flashcards in Diseases Deck (52):
deficient in Acid Sphingomyelinease (A-SMase)
get a build up of sphingomyelin
"No man picks (Nieman pick ) his nose with his SPHINGer (sphingomyelin)
cherry red spot in eye,
enlargement in liver, spleen, neuro. damage.
build up of cholesterol in the carb. shell called glycocalyx on membranes (it's outer shell)
incompatibility btwn. mom and fetus bc mom is Rh-
autosomal recessive, mutation in chloride channel that transports Cl- from inside cell to outside in airways and sweat ducts. The Cl attracts Na+ to make NaCl salt. This then incr. . This makes water go into airway cells to compenaste for aslinity, and decr. water on surface of mucous layer.
Thicker mucous, incr. bac. infections
uptake/reabsorption defected in PCT transporter of dimeric Cystine affected. Along with Arginine, Lysine, Ornithine.
"COLA" Cystine, Ornithnine, Lysine, Arginine
Cystine crystals/stones in kidney
renal cholic (abdominal pain linked to stones)
defect in transporter for non-polar and neutral AAs (alanine, valine, threonin, leucine, tryptophan)
cerebellar ataxia (no muscle coordination)
photodermatitis and photosensitivity
defect in glycolytic enzymes?
issue for RBC, so
hemolytic anemias (premature destruction of rbcs)
markers: elevated lactate dehydrogenase, unconjugatged bilirubin
deficient in PfK-1, the rate limiting step in glycolysis
hemolytic anemia, jaundice and bilirubin is high
Fructose 1,6 Bisphosphate deficiency
similar to Tarui disease, in infancy
hypoglycemia, lactiv acidosis, apnea, hyperventilation
Mutation in rate limiting step of Gluconeogeneis
Von Geirke Disease (GSD1a)
deficient in glucose 6-phosphate
glucose cant get freed at the end of gluconeogenesis
diet can help with managmeent
mutation in GLUT 2 transporter, so many cells in liver, pancreatic beta, enterocytes, and renal tubular cells cannot take up:
glucose, fructose, galactose
treat with vit. D, phosphate
def, in glucose 1P uridyltransferase (GALT) which leads to accumulation of galactitol
"FAB GUT = Fructose is to Aldolase B as Galactose is to UridylTransferase"
def. in galactokinase (type II) accumulate in blood and urin, eye cataracts* "GalactoKInase def. is KINder, benign condition)"
Type 2 diabetes
reduce sensitivity to insulin
normal diabetic is 70-100 mg/dL
Name the glycogen storage diseases:
For types I-V "Very Poor Carbohydrate Metabolism"
GSDI, von Gierke dis.
GSD II, Pompe dis.
GSD III, Cori disease
GSD IV, Andersen disease
GSD V, McArdle dis.
GSD VI, Hers Dis.
GSD VII, Tarui dis
cannot synth. glycogen
alpha 1-6 glucosidase (debranching enzyme)
glycogen have large number of short branches
glucosyl (4:6) transferase (branching enzyme)
pt. have long chain glycogen, fewer branches
Mcardle = Muscle, Myoglobinuria (red urin)
def. in muscle glycogen phosphorlylase
rate lim. step of glycogen breakdown, pt cant supply muscles w/ enough glucose
def in liver glycogen phosphorylase
no glycogen breakdown in liver, accumulates there = hepatomegaly
low blood glucose levels
"PomPe trashes the PumP, 1,4"
Lysosomal acid alpha 1-4 glucosidase w/ alpha 1-6 glucosidase activity (acid maltase)
in lysosomal glycogen degradation
accum. glycogen in lysosome
treat with ERT, enzyme replacement therapy
Mutation in glycogen phosphorylase (GP), does it matter if its in liver or muscle?
liver GP = hers disease
muscle GP = McArdle syndorme
pyruvate carboxylase deficiency
pyruate cant produce oxaloacetate, so goes to different pathways to make lactic acid and alanin
no oxaloacetate prevents gluconeogenesis and urea cycle function
defect in Krebs cycle.
**test for fumarate in the urine.
lethal or causes mental retardation
What drug used to treat HIV but blocks e- transport chain and is called the "uncoupler"?
2,4 Dinitrophenol (DNP), and Zidovudin (AZT)
Mutation in SuperOxidee Dismutase (SOD1)
free radicles form bc O2- forms at end of ETC, and no SOD is there to neutralize the free radical. These can damage proteins, and this case,
ALS has incr. of protein aggregates
What blocks the NADH dehydrogenase (complex I) in the ETC?
Amytal: barbiturate used to treat insomnia, tnesion, anxiety, epilepsy
Rotenone: for pest control. inhaled, human helath hazard
these overall block flow of e- form NADH to CoQ (ubiquinone) and no ATP can be formed from NADH. FADH2 can make 1.5ATP
Medium Chain acyl coenyme A dehydrogenase (MCAD)
issue of FA-beta-oxidation that wont let body break down MCFAs into acetyl-CoA
If ID befroe onset of symptoms, good prognosis.
Treatment: fasting when body needs FA beta oxidation for energy (aka dont fast bc no fatty acid stores can be used)
relies on glucose
X-Linked adrenoleukodystrophy (ALD)
inherited demylenation bc deect in transport of VLCFA CoAs into peroxisomes;
def. ALD protein, which is made from ABCD1 gene and perosisomal VLCFA CoA transporter
accumulation of lignoceric acid (24:0)& cerotic acid (26:0) in:
brain, adrenals of children
stifness in legs, impaired vision, beh. probs.
Females get on one X chromo, shows in middle age
Refsum disease (ARD)
Phytanic acid, from chlorphyll, branch chain fa humans get from dairy, fish, ruminant animals.
Cant be broken down by beta oxidation bc of the 3-methy group.
only substrate by alpha-oxidation in peroxisomes.
Def. in: phytanoyl CoA hydroxylase
accumulation of phytanoic acid.
infant refsum disease
in Zellweger spectrum
mutation in genes for peroxins proteins for peroxisome assembly
in infants with decr. cerebral mylenation
hearing & vision loss,
hypoglicine A, toxin in unripe fruite of akee tree in west africa
transport of beta oxidation of long chain fatty acids inhibited
Hyperhomocysteinemia & Homocystinuria
def. metabolism of homocystein
def. in B6, B12, folic acid)
cystathionin beta synthase def. inherited
Methionin must be decreasted, incr. cystein and B6 to
eye lens dislocation
Vascular (risk factor for atherosclerosis, heart disease, stroke)
Maple syrup urine disease
def. in branched chain alpha keto acid dehyrdrogenase complex (BCKD)
(Isoleucine, Leucine, Valine)
"I Love Vermont maple syrup from Branches."
branched chain AAs in urin, maple syrup smell
in mennonite, amish, jewish
PKU, def. in
phenylalanine hydroxylase (PAH)
Phe cant be converted to Tyr, and eventually cannot make Fumarate
limit Phe and aspartame in diet.
lack of melanin, partial or complete absence of pigmentation in skin
tyrosine to melanin conversion blocked bc.
def. in homogentisate oxidatse
the enzyme in Tyr degradative pathway that leads to making fumerate for TCA
accumulation of homogentisic acid forms pigment in skin
test for dark urine
, darkened sclera
Hyperthyroidism (Graves diseas)
treated with carbimazole and propylthiouracil: these block iodination of thyroglobulin in the thyroperoxdiase in follicular lumen, decr. T3, T4
exces ammonia from ura cyvle or liver failure:
toxic to Brain and CNS
depletion of glutamate
Urea cycle and high prtoein diet
low carb, high protein incr. urea production
Some anti-cancer agents drugs ?
PURINE synthesis affected
competitive inhb. for enzymes that use folate.
Prevents oxidation of NADPH by DHFR
stop production of DNA in cancer cells
5-Fluorouracil, (inhb. Thymidylate synthase) an antimetabolite of pyrimidines
for breast, ovarian, gastric, pancreatic, colorectal cancer.
Treat with oral uridine.
def. in UMP synthase
(During pyramiding synth)
excess. orotic acid in urin
cant convert Oric Acid to UMP
this drug resembles nucleosides that the virus favors more than its normal nucleoside analogue. will need GTP. ONce the virus tries to put the acyclovir into DNA, it lacks a
Thymidine Kinase (TK)
***and ends DNA replication
Viral supression for:
chicken pox lesions
inflamed joints (commonly big toe, metatarsal pharangeal joint)
disease of the wealthy
MSU (Monosodium Urate) crystals
high concentration, low temps, maks Na-ions crystalize
what can be tested for Urine to see the breakdown of dTDP, and dTTP
defect in HGPRT enzyme (hypoxanthineguanin phosphoribosyltransferase) whihc works in purine salvage pathway
"HGPRT = Hyperuricemia, Gout, Pissed off (self mutilation, aggression, Retardation, dysTonia"
cannot conver Guanine, Hypoxanthine, to CMP or IMP
overproduce uric acid
kidney stones, itchy everywhere, self mutilation :(
What do sulfa drugs do?
disrupt bacterial DNA replication selectivly
What s 5-fluorouracil?
Affects Pyrimidine Nucleotide formation
___ causes premature destruction of RBCs, and ___m causes SCID (severe combined immunodeficiency).
1. Overproduction of ADA (adenosine deaminase)
premature destruction of adenosine
2. Under production of ADA
African word for malnutrition after weening breast feeding.
Protein defecient and malnourished. Skin lesions, swollen abdomin
Liver (fatty change)
extreme malnutrion, but not causing edema. Diet deficeint in calories. Child doesnt want to eat anymore, bonier.
"Marasmus results in Muscle wasting"
Purine synth commuted step? Drugs associated with this cycle?
2nd step, glutamine phosphoribosyl pyrophosphate amidotransferase
Methotrexate: compet inhibitor folate. Inhb DHFR
Sulfa Drugs: disrupt DNA replication in bacteria