topic 4 Flashcards
Hb with O2
Oxyhemoglobin (oxyHb)
Hb without O2
Deoxyhemoglobin (deoxyHb)
contains Fe3+ instead of Fe2+ in heme groups
Methemoglobin (metHb)
CO binds to Fe2+ in heme in case of CO poisoning or smoking. CO has 200x higher affinity to Fe2+ than O2.
Carbonylhemoglobin (HbCO)
CO2 is non-covalently bound to globin chain of Hb. HbCO2 transports CO2 in blood (about 23%).
Carbaminohemoglobin (HbCO2)
is formed spontaneously by nonenzymatic
reaction with Glc. People with DM have more HbA1c than normal (› 7%).
Measurement of blood HbA1c is useful to get info about long-term control of glycemia
Glycohemoglobin (HbA1c)
are cyclic compounds that bind metal ions (usually Fe2+ or Fe3+)
Porphyrins
are porphyrin precursors
intermediate between porphobilinogen & protoporphyrin
Porphobilinogen Porphyrinogens Protoporphyrins
Porphyrinogens
• are hereditary or acquired disturbances of heme synthesis
• in all cases there is an identifiable abnormality of the enzymes which synthesize heme
PORPHYRIAS - DISTURBANCES OF HEME SYNTHESIS
are rare inherited defects in heme synthesis.
● An inherited defect in an enzyme of heme synthesis results in accumulation of one or more of porphyrin precursors depending on location of block of the heme synthesis pathway.
PORPHYRIAS
▶ Chronic hepatic porphyria
▶ The most common type of porphyria
▶ a deficiency in uroporphyrinogen decarboxylase
▶ Clinical expression of the enzyme deficiency is influenced by various
factors, such as exposure to sunlight, the presence of hepatitis B or C
▶ Clinical onset is during the fourth or fifth decade of life.
▶ Porphyrin accumulation leads to cutaneous symptoms and urine
PORPHYRIA CUTANEA TARDA
Porphyrias leading to accumulation of ALA and porphobilinogen cause abdominal pain and neuropsychiatric disturbances, ranging from anxiety to delirium.
Acute Intermittent Porphyria
often precipitated by administration of drugs such as barbiturates and ethanol.
ACUTE HEPATIC PORPHYRIAS
most serious case of porphyria - very rare
Congenital Erythropoeitic Porphyria
is a hemoprotein only found in the cytoplasm of (ery) transports O2 and CO2 between lungs and vario
HEMOGLOBIN (HB)
STRUCTURE OF HEMOGLOBIN
spherical molecule consisting of 4 peptide subunits (globins) = quartenary structure
- is a single-chain globular protein of 153 AA, containing 1 heme group
- transports O2 in skeletal and heart muscle
- is found in cytosol within cells
- is a marker of myocard damage
MYOGLOBIN (MB)
- synthesis of heme starts in mitochondria
- succinyl-CoA and Gly undergo a condensation → ALA
- reaction is catalyzed by enzyme ALA synthase
Δ-AMINOLEVULINIC ACID (ALA)
- oxidation of protoporphyrinogen IX produces the conjugated π- electrone system of protoporphyrin IX
PROTOPORPHYRINOGEN IX → PROTOPORPHYRIN IX
is a key regulatory enzyme
ALA synthase
the major form of Hb in adults and in children over 7 months.
HbA1
is a minor form of Hb in adults. It forms only 2 – 3% of a total Hb A.
HbA2 (2 α, 2 δ)
in fetus and newborn infants Hb F binds O2 at lower tension than Hb A
Fetal Hb (Hb F) = 2 α and 2 γ subunits
an abnormal Hb typical for sickle cell anemia
Hb S – in β-globin chain Glu is replaced by Val
INHERITED AUTOSOMAL RECESSIVE BLOOD DIASEASES
genetic defect results in reduced rate of synthesis of α- or β-globin chain → it causes the formation of abnormal Hb molecules → anemia
• are prevalent in populations where malaria was endemic – Arab-Americans, people of Mediterranean origin and Asians
• genetic counseling and genetic testing is recommended for families that carry a thalassemia trait
THALASSEMIAS
