PK deficiency Flashcards
what is the prevalence?
1:20,000 in the general white population
what are the most prevalent mutations?
l529A–most common in USA, northern europe, and central europe; l456T–southern europe; l468T–prevalent in asia
most common severe mutation in Caucausians?
G332S
PK deficiency is an autosomal recessive trait
ya
Symptoms of PK deficiency
restricted to erythrocytes–hemolytic anemia (depends on degree of enzyme activity and cellular 2,3 BPG levels); jaundice, splenomegaly; increased incidences of gallstones
Types of patients with PK def
early onset: severe jaundice and hemolytic anemia; many transfusions needed and a splenectomy may be performed; growth is normally unaffected, but some retardation have been found;
late–usually no symptoms, only during pregnancy or illness
PK isoforms in mammalian tissue
L-type–liver, renal, small int.; R-RBC; M1–skeletal muscle, heart, and brain; M2–dominant fetal form, also in adult WBC and platelets
PKLR gene codes L & R, PKM codes M1 & 2
ye
regulation of PK isoforms
PK L, R, & M2 are all activated by F-1,6-BP; PK L R covalently modified–dephos, active, phos, inactive; M2–inactive in dimer form, active in dimer form– M1 not regulated, always has high activity
Effects on RBCs when PK activity is deficient
ATP goes down, pyruvate goes down, all glycolytic intermediates go up, and 2,3-BPG goes up
How does BPG affect RBCs?
as 2,3 BPG conc increases, it competes with O2 for binding to Hb–>compared to a hyperbolic pO2 curve with no BPG, the amount of O2 in tissues goes down significantly; also goes down in lungs, but not as much
As you increase bpg, how much does O2 go down in the tissues by?
30-40%
Why does the spleen need to be removed for PK deficient patients?
the spleen ends up destroying the RBC–when there is not enough energy (ATP) the cell membrane cannot maintain its function, so Ca2+ enters the cells while K and H2O leave, thus dehydrating the cell–>causes clls to change shape and be phagocytosed by the reticuloendothelial system of the spleen
How is bilirubin excreted from the body?
heme–>bilirubin–>Bb+albumin–> Bb+albumin+UDP-glucuronate (Bb diglucuronide, conjugated Bb)–>excreted out in bile`
detox pathway
glucose–>g6p–>G1P–>UDP-glucose–UDP-glucose DH–>UDP-glucuronate +2NADH+2H–UDP-glucuronosyl transferase (ER)–>glucuronide + UDP–>excretion in bile or urine
