Iron Metabolism

Description

Biochemistry Mind Map on Iron Metabolism, created by hardinbc on 02/05/2013.
hardinbc
Mind Map by hardinbc, updated more than 1 year ago
hardinbc
Created by hardinbc over 11 years ago
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Resource summary

Iron Metabolism
  1. Reactions
    1. redox
      1. accept e-
        1. ferrous (Fe2+)
        2. donate e-
          1. ferric (Fe3+)
          2. physiology
            1. electron transport
              1. Fe-S clusters, cytochromes
                1. respiratory chain
            2. pathophys
              1. free Fe
                1. lipid peroxidation
                  1. PUFAs
                    1. atherogenesis
              2. Fenton
                1. free radical formation
                  1. ROS
                    1. H2O2
                  2. free iron
                    1. injured tissue
                      1. breakdown of heme
                  3. Distribution
                    1. major
                      1. hemoglobin
                        1. RBC
                          1. 1800 mg
                      2. minor
                        1. muscle fibers
                          1. 300 mg
                          2. liver
                            1. 1000 mg
                            2. macrophages
                              1. 600 mg
                          3. Transport/Storage
                            1. plasma
                              1. transferrin
                                1. 30% saturated
                              2. cell storage
                                1. ferritin
                                  1. interact w/ ceruloplasmin or hephaestin
                                    1. binds transferrin
                                      1. transported
                                2. other binders
                                  1. neutrophils
                                    1. lactoferrrin
                                    2. tissue injury
                                      1. hemosiderin
                                      2. mitochondrial storage protein
                                        1. frataxin
                                    3. Steps of Metabolism
                                      1. 1) intestinal absorption of ferrous
                                        1. stomach
                                          1. low pH
                                            1. reduce iron (III) --> (II)
                                          2. intestines
                                            1. alkaline environment
                                              1. heme
                                                1. direct absorption
                                                  1. mucosal cells
                                                    1. iron dissociates
                                                    2. free iron
                                                      1. oxidized
                                                        1. (II)-->(III)
                                                          1. reduced again
                                                            1. taken up by mucosal
                                              2. transport across epithelium
                                                1. apical
                                                  1. DMT1
                                                  2. basolateral
                                                    1. ferroportin
                                                      1. requires hepaestin
                                                  3. regulation
                                                    1. dietary regulator
                                                      1. short term
                                                        1. decrease DMT1
                                                        2. stores regulator
                                                          1. hepcidin
                                                            1. responds to total body iron
                                                              1. 25 aa peptide
                                                                1. regulate export
                                                                  1. intestinal cells
                                                                    1. macrphages
                                                                      1. hepatocytes
                                                                      2. inactivates ferroportin
                                                                        1. induces internalization
                                                                          1. lysosomal degradation
                                                                        2. synthesis regulation
                                                                          1. activates
                                                                            1. inflammation
                                                                            2. inhibits
                                                                              1. iron deficiency
                                                                                1. increased erythropoiesis
                                                                                  1. hypoxia
                                                                            3. erythropoietic regulator
                                                                              1. modulate reabsorption based on erythropoiesis requirements
                                                                                1. no reponse to iron
                                                                          2. 3) cellular uptake and storage in ferritin and frataxin
                                                                            1. transferrin receptor
                                                                              1. uptake at PM
                                                                                1. di-ferric transferrin internalized
                                                                                  1. endocytosis
                                                                              2. regulation
                                                                                1. IRP-1
                                                                                  1. cytosolic aconitase
                                                                                    1. RNA binding protein
                                                                                      1. cells iron depleted
                                                                                      2. cell ironreplet
                                                                                      3. senses iron depletion/oxidative stress
                                                                                        1. activation
                                                                                          1. binds 2 mRNAs
                                                                                            1. ferritin IRE
                                                                                              1. 5' untranslatable regioon
                                                                                                1. inhibits translation
                                                                                              2. transferrin receptor
                                                                                                1. 3' untranslatable region
                                                                                                  1. increases translation
                                                                                              3. overall effect
                                                                                                1. decrease ferritin synthesis
                                                                                                  1. increase transferrin receptor synthesis
                                                                                                    1. increase cellular uptake
                                                                                          2. 2) plasma transport by transferrin
                                                                                            1. Fe (III) delivered to apo-transferrin
                                                                                              1. transport to diff tissues
                                                                                                1. binds 2 Fe (III) atoms
                                                                                                2. from bone marrow
                                                                                            2. Nutrition
                                                                                              1. dietary sources
                                                                                                1. liver, red meat, eggs, whole grain, dried fruit, beans, drinking water, iron cooking pots
                                                                                                  1. SPINACH
                                                                                                2. absorption
                                                                                                  1. enhanced
                                                                                                    1. ascorbic acid, dietary protein, erythropoiesis, hypoxia, low stores
                                                                                                    2. inhibited
                                                                                                      1. oxalic acid, coffee, tea, bran, egg yolk, soybean products, calcium, polyphenols, excess metals, inflammation, achlorydria
                                                                                                    3. excretion
                                                                                                      1. limited capacity
                                                                                                        1. transferrin bound
                                                                                                          1. not excreted in kidney
                                                                                                          2. chelators
                                                                                                            1. excretable
                                                                                                          3. hemorrhage
                                                                                                        2. Disease
                                                                                                          1. deficiency
                                                                                                            1. anemia
                                                                                                              1. impaired immune resonse
                                                                                                                1. initial
                                                                                                                  1. no symptoms
                                                                                                                  2. diagnosis
                                                                                                                    1. < 20% transferrin sat
                                                                                                                    2. treatment
                                                                                                                      1. ferrous sulfate
                                                                                                                        1. packed RBCs
                                                                                                                      2. iron overload
                                                                                                                        1. acute iron poisoning
                                                                                                                          1. hypotension
                                                                                                                            1. metablolic acidosis
                                                                                                                              1. coma
                                                                                                                              2. chronic iron overload
                                                                                                                                1. patients who receive transfusions
                                                                                                                                  1. congenital anemias
                                                                                                                                2. ineffective erythropoiesis
                                                                                                                                  1. increased iron absorption
                                                                                                                                    1. certain anemias
                                                                                                                                      1. destroy erythrocytes in bone marrow
                                                                                                                                        1. signal erythroid regulator
                                                                                                                                          1. increased iron absorption
                                                                                                                                    2. conditions
                                                                                                                                      1. thalassemias
                                                                                                                                        1. sideroblastic anemias
                                                                                                                                    3. Hereditary Hemochromatosis HH)
                                                                                                                                      1. iron overload
                                                                                                                                        1. mutation
                                                                                                                                          1. HFE gene
                                                                                                                                            1. caucasian
                                                                                                                                              1. carrier = 1/10
                                                                                                                                            2. TFR2
                                                                                                                                              1. HJV
                                                                                                                                              2. absorb/store too efficiently
                                                                                                                                                1. symptoms
                                                                                                                                                  1. iron accumulation
                                                                                                                                                    1. oxidative damage in these tissues
                                                                                                                                                      1. liver
                                                                                                                                                        1. cirrhosis
                                                                                                                                                        2. heart
                                                                                                                                                          1. cardiomyopathy
                                                                                                                                                          2. pancreas
                                                                                                                                                            1. DM
                                                                                                                                                            2. skin
                                                                                                                                                              1. pigmentation
                                                                                                                                                              2. joints
                                                                                                                                                                1. polyarthropathy
                                                                                                                                                                2. gonads
                                                                                                                                                                  1. hypogonadotrophic hypogonadism
                                                                                                                                                            3. treatment
                                                                                                                                                              1. phlebotomy
                                                                                                                                                                1. chelators
                                                                                                                                                                2. before organ damage
                                                                                                                                                              2. Anemia of chronic disease (ACD)
                                                                                                                                                                1. impaired utilization of iron
                                                                                                                                                                  1. no deficiency/excess
                                                                                                                                                                  2. defect
                                                                                                                                                                    1. blockage
                                                                                                                                                                      1. stores --> erythroid precursors
                                                                                                                                                                    2. treatment
                                                                                                                                                                      1. underlying cause
                                                                                                                                                                      2. disease leads to ACD
                                                                                                                                                                        1. chronic infections
                                                                                                                                                                          1. inflammatory bowel disease
                                                                                                                                                                            1. neoplasia
                                                                                                                                                                              1. autoimmune disease
                                                                                                                                                                                1. mechanism
                                                                                                                                                                                  1. inflammatory cytokines
                                                                                                                                                                                    1. IL6
                                                                                                                                                                                      1. Hepcidin upregulated
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