heme metabolism and storage
Terms in this set (64)
heme in myoglobin used for
heme in hemoglobin used for
heme in cytochromes used for
heme in cytochrome P450 enzymes used for
addition of O to lipids
heme in catalase used for
degradation of H2O2
heme in nitric oxide synthase used for
formation of NO signaling
heme in peroxidases used for
degradation of peroxides
heme synthesis occurs primarily in the
liver and bone marrow
synthesis of heme begins with
glycine and succinyl CoA
what is required for the conversion of glycine and succinyl CoA to ALA?
pyriodxal phosphate and ALAS1
heme acts as feedback inhibitor to
lead poisoning halts heme synthesis in the cytoplasm and prevents ________ formation in the cytoplasm
What are the symptoms of lead poisoning in children?
isomnia, irritability, malasie and anemia, lapse in concentration, coordination
symptoms of lead poisoning in adults
abdominal pain, memory loss, kidney failure, general fatigue/weakness
what is the treatment for lead poisoning?
chelation therapy with dimercaptosuccinic acid
reduces transcription of ALAS1 gene and induces degradation of ALAS1 mRNA; heme is converted to to this when it is overproduced
can be used therapeutically to regulate heme production (minimize heme production)
in erythrocytes _______ is the isozyme found and it is also regulated by the availability of Fe2+
what charge state is hemin in?
Fe3+ instead of Fe2+
conditions which result from specific enzyme deficiencies in the heme synthetic pathway
stops the addition of Fe2+ pre-heme protoporphyrin IX but the mechanism of this is unclear
sunlight sensitivity is seen in porphyria which have accumulation of what?
porphyrin or porphyrinogen
generally treat porphyria with what?
hemin and glucose
most common porphyria; most often "acquired" due to alcoholism, liver damage, or excessive Fe intake; produces NO neurological or abdominal symptoms; patient present with cutaneous photosensitivity and altered urine color (red)
porphyria cutanea tarda
what enzyme is deficient in PCT and because of this what compound will begin to accumulate?
uroporphyrinogen decarboxylase; uroporphyrin will accumulate in the urine
blistering in PCT is due to a photoreactive __________ in skin; found wherever skin is exposed to sunlight
minimal clinical occurrence; observe abdominal pain, constipation, muscle weakness, cardiovascular abnormality; activity of hydroxymethylbilane synthase is reduced; neurological sympotoms
acute intermittent porphyria
what enzyme is defective in AIP?
what begins to accumulate in AIP?
ALA and porphobilinogen
What happens to urine in patients suffering from AIP?
urine will darken when exposed to air
chronic disease caused by a deficiency in ferrochelatase; protoporphyrin accumulates in erythrocytes, bone marrow, and plasma; patients are photosensitive
what are the 5Ps associated with AIP?
porphobilinogen deaminage defieincy, pain in the abdomen, peripheral neuropathy, pee abnormally, precipitated by drugs
acute attacks of AIP result from...
drugs which induce CYP expression, requiring more heme production
what enzyme is defective in EPP?
accumulation of protoporphyrin in EPP leads to
due to lack of working ferrochelatase in EPP leads to accumulation of what?
EPP is not associated with what? this is a major difference between it and PCT
no discoloration of the urine
what enzyme catalyzes 3 successive reactions involving O2 and NADPH in heme degradatoin?
heme oxygenase opens porphyrin ring into _________ and releases CO2, which can induce inflammation
what color tint does biliverdin have to it?
biliverdin is reduced to
what color tint does blurb have to it?
the first 3 steps of heme degradation occurs in what?
insoluble in blood/plasma and is transported into the blood via non covalent binding to alubumin
how is bilirubin transferred in the blood?
by non-covalently binding to albumin
bilirubin enter the liver and is conjugated with _______ _____ to increase its solubility
defieincy of what enzyme leads to gilbert syndrome?
benign but individuals with this disease will have test results indicating hyperbiliurbinemia
bilirubin diglucorunide is actively transported into
interference with the active transport of conjugated bilirubin into the bile is often found in what kind of diseases?
in the small intestine conjugated bilirubin is hydrolyzed and converted to
urobilinogen (by bacteria)
urobilinogen is oxidized to what?
what product of heme degradation gives feces its characteristic brown color?
some urobilinogen is transport dot kidneys via bloodstream and converted to _______, which gives urine it characteristic yellow color
barely soluble in water; moves through bloodstream bound to albumin; cannot be excreted in the urine regardless of how high blood levels reach
this syndrome is fatal at birth because bilirubin UDP-glucouronyl transferase is completely non-functional
type 1 crigler-najjar syndrome
also called "icterus"; yellow skin and sclera are indicative of some underlying disorder
hemolysis in RBC is occurring at a rate greater than what the liver can clear; usually associated with sickle cell anemia, pyruvate kinase deficiency, and g6p dehydrogenase defieicency
damage to liver cells causes unconjugaed bilirubin levels in bloodstream to rise; urobilinogen also increases, leading to darker coloration of the urine; feces may have lighter color due to decreased urobilinogen entering the small intestines (and thus reduced stercobilin)
due to obstruction of the bile duct conjugated bilirubin does not pass into the small intestines but is diverted into the bloodstream; patients will often note abdominal pain and nausea; stool will lack sstercobilin and have reduced brown coloration or are pale; urine will lack urobilin but will have higher levels of conjugated bilirubin which darkens when exposed to air
an encephalopathy where the bilirubin causes swelling in the basal ganglia
bilirubin UGT activity is minimal in newborns, esp pre term; serum albumin can bind some unconjugated but excess bilirubin can cause kernictuerus and irreversible neurological damage; treat with exposure to UV lamps
caused by impaired bile formation or conjugated bile flow to the duodenum and resulting accumulation of bile pigment in the liver itself
may observe jaundice, pale stool, local accumulations of cholesterol, or symptoms of vit A, D, E, or K deficienceies