Biochemistry - Unit III - Heme, Hb, Vitamins

  1. The porphyrins are heterocyclic ring structures that include ___ pyrrole rings joined together through carbon (methenyl) bridges. The most abundant porphyrins in nature are found in hemoglobin and the chlorophylls. In the center of porphyrins a metal atom is chelated to the ___ atoms of the pyrrole units. In heme and related porphyrins this metal atom is ___. In chlorophyll the metal atom is magnesium.
    • four
    • nitrogen
    • iron
  2. Porphyrin Synthesis: step 1
    • glycine + succinyl CoA -> 5-aminolevulinate (ALA)
    • rate limiting step
    • catalyzed by ALA synthase (5-aminolevulinate synthase, δ-aminolevulinate synthase)
    • inhibited by heme (neg feedback)
    • linear structure
  3. Porphyrin Synthesis: step 2
    • two 5-aminolevulinate -> monopyrrole, porphobilinogen
    • still linear; in later steps cyclization, condense, eventually forms heme
    • catalyzed by ALA dehydratase (Porphobilinogen Synthase)
    • inhibited by lead
    • the last step is catalyzed by Ferrochelatase, which is also inhibited by lead
  4. The first reaction and the last three reactions of heme synthesis occur in _______ with the other four reactions being in the _____.
    • mitochondria
    • cytosol
  5. Regulation of hemoglobin synthesis involves balancing of ______ and ______ synthesis via accumulation of ____, or ______, its spontaneously oxidized free form, which inhibits ________ (synthesis and functioning), and activates _______.
    • porphyrin
    • polypeptide
    • heme
    • hemin
    • ALA synthase
    • the synthesis of globin peptide
  6. Hemin inhibits ALA synthase both in the _______ synthesizing hemoglobin and in other cells in which _______ are made.
    • primitive red blood cell
    • the cytochromes and other heme proteins
  7. Porphyria
    • heme synthesis disorders
    • other than lead poisoning and acute intermittent porphyria (affect the earliest steps in heme synthesis, no porphyrin structure produced yet), all show light sensitivity, due to the accumulation of porphyrin
    • skin, abdominal pain, neuropsychiatric
  8. Porphyria Cutanea Tarda
    The most common porphyria
  9. Protoporphyria
    deficiency in Ferrochelatase
  10. Degradation of red cell
    • heme -> billirubin, heme oxidase, by macrophages
    • apoprotein -> AAs
    • heme is opened and subject to oxidation to yield biliverdin, iron and carbon monoxide
    • iron is reutilized
    • Biliverdin: reduced to bilirubin by biliverdin reductase
    • Bilirubin: transferred to liver as bilirubin-albumin complex. made more soluble in liver by conjugation with glucuronic acid from UDP-glucuronic acid, catalyzed by glucuronate transferase.
  11. hemolytic anemia
    • increased breakdown of hemoglobin
    • causes increase in billirubin, hyperbilirubinemia
  12. Jaundice
    the clinical syndrome associated with elevated serum level of bilirubin (>1 mg/dl)
  13. Oxygen transport is mediated by two heme proteins:
    • myoglobin: muscle; a single polypeptide chain
    • hemoglobin: red blood cells; four polyeptide chains
  14. ________ is the major Hb type in adults and has _______ chains. Each subunit has a _______ containing ________.
    • Hemoglobin A
    • two alpha and two beta
    • hydrophobic pocket
    • the heme unit
  15. oxygen affinity of heme proteins
    • Myoglobin:
    • greater affinity for oxygen
    • rectangular hyperbola oxygen binding curve 
    • Hb:
    • sigmoidal oxygen binding curve
    • cooperativity exists in the binding of the four oxygen molecules.
    • The binding of oxygen to hemoglobin is decreased by a decrease in pH (Bohr effect) and by an increase in the level of 2,3-bisphosphoglycerate.
  16. the iron in hemoglobin must be maintained in the ______ state for the transport of oxygen.
  17. Oxidation of the iron of hemoglobin (Fe2+ -> Fe3+) forms _______, which can be caused by _____ and some drugs.
    The reverse of this process can be achieved by several _________ enzymes.
    • methemoglobin
    • nitrite
    • NADH or NADPH-linked
  18. The cooperativity in binding the four O2 molecules involves two conformational states:
    • T (tense) and R (relaxed).
    • Binding of oxygen to one subunits favors conversion from T to R state
    • R state has a higher affinity for oxygen.
  19. lower pH results in
    • lower O2 affinity
    • right shift
    • greater pO2 needed to reach the same level of saturation
  20. increase 2,3-BPG results in
    • right shift
    • happens in adaptation to high altitudes
  21. Glucosylation of hemoglobin occurs in ______  and may serve to measure _____.
    • diabetes mellitus
    • chronic elevation of blood glucose levels
  22. One of the most important hemoglobinopathies of genetic origin is ________: occurs when the individual is _______ for a point mutation of substitution of ____ for ____ in the ___ subunits; causing hemolytic anemia, painful crises and poor circulation.
    • sickle cell anemia
    • homozygous
    • valine
    • glutamate
    • beta
  23. The thalassemias are a group of hereditary diseases in which there are defects in the synthesis of _________.
    either the alpha or the beta chains
  24. Both thalassemias and sickle cell anemia are found in __________.
    • individuals of genetic origins from areas historically affected by malaria
    • both have certain resistance to it
  25. Carbon monoxide binds to hemoglobin _____ than oxygen and it ______ oxygen release.
    • more tightly
    • prevents
  26. Vitamins are ____ compounds ________ in small amounts. They are conveniently classed as ________.
    • organic
    • required in the diet
    • fat soluble (A, D, E and K) or water soluble (C and the B complex)
    Function: _____ is a precursor for _____ that is used in the ______ and for ________ that is required for maintenance of ______ cells. In the visual cycle, ___ binds the ____. Light causes the conversion to the ____ isomer which is ______ bound to opsin.
    _____ can be metabolized to form vit A
    Oxidation of retinal to retinoic acid is ______ and functions as _______.
    • Retinol
    • retinal
    • visual cycle
    • retinoic acid
    • epithelial
    • opsin
    • 11-cis isomer of retinal
    • all-trans
    • only weakly
    • beta-carotene
    • irreversible
    • a ligand for nuclear receptors that function in the regulation of gene transcription
  28. Thiamine (B1)
    Function: Thiamine is converted to thiamine pyrophosphate which is a cofactor for _______ of alpha-keto acids and for _______ (pyruvate decarboxylases and AKG decarboxylases)
    Effect of Deficiency: ______ syndrome. _____, cardiac pathology, edema
    • oxidative decarboxylation
    • transketolase
    • Beriberi (polished rice) and Wernicke Korsakoff
    • Polyneuritis
    Function: precursor for the coenzymes, _____.
    Effect of Deficiency: atrophy of ______, ______
    • FMN and FAD
    • filliform papillae
    • angular cheilosis
    Function: As nicotinic acid or ____ it is a precursor for the coenzymes _______.
    Some niacin can be synthesized from _____.
    Effect of Deficiency: ______
    • nicotinamide
    • NAD and NADP
    • tryptophan
    • Pellagra (dermatitis, diarrhea, dementia and if severe, death)
    Function: Pyridoxine (pyridoxol) is a precursor of _______  which is a coenzyme for enzymes catalyzing ________ and for ________.
    • pyridoxal phosphate
    • transamination, deamination, decarboxylation
    • glycogen phosphorylase
  32. BIOTIN
    Function: Biotin acts as a coenzyme in _________ reactions in covalent linkage to ____ side chains of enzymes.
    Strongly bound by _____ in raw eggs.
    Deficiency is ___
    • carboxylation
    • lysine
    • avidin
    • rare
    Function: Pantothenic acid is a precursor of _____. This structure forms part of ______.
    • pantotheine
    • coenzyme A
    Function: Folic acid is a precursor for ______ that is used as a carrier of _____ at different levels of ____.  needed for purine, thymine synthesis, amino acid metabolism.
    Effect of Deficiency: _______, ________.
    • tetrahydrofolate THF
    • one carbon units
    • oxidation
    • Megaloblastic anemia
    • GI disturbances
  35. VITAMIN B12 (______)
    Function: precursors of cofactors used for: I. conversion of ________; II. conversion of ______.
    Vitamin B12 is absorbed from the ____ as a complex with ______ which is produced by the gastric mucosa.
    Effect of Deficiency: _______ and _______.
    • methylmalonyl CoA to succinyl CoA
    • homocysteine to methionine
    • ileum
    • intrinsic factor
    • Pernicious anemia (not correctable by iron administration)
    • degeneration of spinal cord neurons
  36. VITAMIN C (______)
    Function: a water soluble _____; promotes the hydroxylation of proline residues of ___. Ascorbic acid is also required in the synthesis of ______.
    Effect of Deficiency: ____ (_______).
    • antioxidant
    • collagen
    • carnitine, dopamine and bile acids
    • Scurvy
    • hemorrhage, impaired wound healing and bone formation
  37. Vitamin D
    Function: Regulation of _____ levels through actions on ________. Vitamin D3 (cholecalciferol) requires conversion to ______ vitamin D3 to form the active compound.
    Effect of Deficiency: ______, _______
    • calcium
    • intestine, kidney and bone
    • 1,25-dihydroxy
    • Rickets
    • osteomalacia
  38. VITAMIN E (________)
    Function: a lipid-soluble ______ and helps to prevent ______.
    • Tocopherol
    • antioxidant
    • lipid damage
  39. Vitamin K
    Function: coenzyme for the carboxylation of glutamic acid side chains (gamma carboxylation, forms two carboxyls, good for binding calcium ions) of some ________.
    Effect of Deficiency: rare; can be associated with ______.
    • blood clotting factors (prothrombin, factors VII, IX and X)
    • prolonged blood clotting times
Card Set
Biochemistry - Unit III - Heme, Hb, Vitamins
Biochemistry - Unit III - Heme, Hb, Vitamins