biochem diseases Flashcards
what happens when there is a loss of one alpha-globin chain?
results in silent carrier
what happens when there is a loss of 2 alpha-globin chains?
results in thalassemia trait (mild symptoms)
what happens when there is a loss of 3 alpha-globin chains?
results in HbH disease (clinically severe)
what happens when there is a loss of all alpha-globin chains?
fetal gamma tetramers will form resulting in Hb Bart disease (fatal in utero because fetal gamma chains have high affinity for O2)
what causes methemoglobinemia?
deficiency in cytochrome B5 reductase
can’t convert Fe3+ to Fe2+
what does no or few beta chains cause?
beta-thalassemia major (Cooley anemia)
requires medication intervention to survive childhood
what does varying beta chain deficits relative to alpha chain cause?
beta-thalassemia intermedia
what does slight deficit in beta chain deficits relative to alpha chain cause?
beta-thalassemia minor
little to no symptoms, low MCV, low beta-globin content
where is EPO produced?
in the KIDNEY in response to low O2 levels
where do reticulocytes mature?
in the spleen where they lose ribosomes and mRNA
what causes inadequate HbB chains?
gene deletion, promoter mutation, and splice-junction mutation
how do protons stabilize the T state of Hb?
protonating HISTIDINE residues in the core of Hb
SHORT TERM regulation of Hb-O2 binding affinity
what is the long term regulator of Hb O2-binding affinity
2,3 BPG which binds to the core of T-state Hb
why are infants more prone to methemoglobinemia?
because they drink well water containing nitrate that can be converted to nitrite in their digestive tract
nitrite can oxidize Hb to metHb
because infants do NOT express enough cytochrome b5 reductase, they cannot reduce metHb to Fe2+
what is the function of haptoglobin?
it binds to Hb that leaks from RBC in circulation
what does a low haptoglobin serum indicate?
intravascular hemolysis
this means that more Hb is leaking from RBC and binding to haptoglobin
what is significant about ALA?
it is a neurotoxin that likely contributes to the symptoms of lead poisoning, both acute and chronic
what happens in ppl with AIP?
they will accumulate porphobilinogen and ALA due to deficiency in porphobilinogen deaminase
upon air oxidation in natural lighting will be red/brown and under fluorescent light will be red/pink
symptoms include ab pain and neuropsychiatric disturbances ranging from anxiety to delirium
treatment = use heme analog, hematin to inhibit ALA synthase because ALA 1 is inhibited by heme
why is B12 important in CN?
hydroxycobalamin binds to CN- and becomes cyanocobalamin to transport it to the kidney or rhodanese
becomes nontoxic form that can be excreted
why is bilirubin and biliverdin important?
they are potent free radical scavengers that protect against ox damage
what enzymes are sensitive to inhibition by lead? what is the result?
ALA dehydratase and ferrochelatase are sensitive to inhibition by lead
inhibition of these enzymes lead to low heme levels which produce microcytic, hypochromic anema
what is sideroblastic anemia?
decreased in vitamin B6 –> decreased heme synthesis because can’t stimulate ALA synthase
results in microcytic, hypochromic anemia with high iron stores
what promotes inhibitors of uroporphyrinogen decarboxylase?
hepatitis and hemochromatosis
what is the importance of vitamin C in iron?
vitamin C is needed to reduce Fe3+ to Fe2+ so that iron can be absorbed by intestinal epithelial cells
REDUCING AGENT
