Pyrimidine Metabolism

Description

Biochemistry Mind Map on Pyrimidine Metabolism, created by hardinbc on 01/05/2013.
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

Pyrimidine Metabolism
  1. Synthesis
    1. glutamine
      1. carbamoyl phosphate
        1. urea cycle
          1. committed step
            1. N-carbamoylaspartate
              1. dihydroorotate
                1. orotate
                  1. + PRPP
                    1. orotidylate
                      1. UMPS
                        1. OPRT
                          1. ODC
                          2. UMP
                            1. UTP
                              1. CTP
                                1. CTP synthetase
                                  1. + ATP
                                2. + ATP
                            2. NAD+ --> NADH
                            3. dehydration
                            4. + aspartate
                              1. aspartate transcarbamoylase
                            5. CPS II
                              1. cytosol
                                1. 2 ATP
                              2. salvage pathway
                                1. thymidine kinase
                                  1. thymidine + ATP
                                    1. TMP + ADP
                                    2. deoxyuridine + ATP
                                      1. dUMP + ADP
                                    3. uridine phosphorylase/uridine kinase
                                      1. uracil + ribose-1-p
                                        1. uridine + Pi
                                        2. uridine + ATP
                                          1. UMP + ADP
                                        3. deoxycytidine kinase
                                          1. deoxycytidine + ATP
                                            1. dCMP + ADP
                                      2. Deoxyribonucleotides
                                        1. NDP
                                          1. dNDP
                                            1. ribonucleotide reductase
                                              1. thioredoxin
                                                1. NADPH reduces
                                                2. (-) hydroxyurea
                                                  1. (+) ATP, (-) dATP
                                                    1. metabolic state
                                                    2. allosteric
                                                      1. dTTP, dGTP, dATP
                                                  2. dUMP
                                                    1. dTMP
                                                      1. + dihydrofolate
                                                      2. thymidylate synthase
                                                        1. + N5,N10-methylenetetrahydrofolate
                                                          1. donates CH3
                                                      3. Regulation of Synthesis
                                                        1. cytoplasmic CPSII
                                                          1. inhibition
                                                            1. UTP
                                                              1. CTP
                                                              2. stimulation
                                                                1. ATP
                                                                  1. PRPP
                                                                2. Catabolism
                                                                  1. ultimate products
                                                                    1. B-alanine
                                                                      1. CMP or UMP
                                                                      2. B-aminoisobutyrate
                                                                        1. dTMP
                                                                        2. CO2
                                                                          1. NH3
                                                                          2. alanine
                                                                            1. malonyl-CoA
                                                                              1. FA synthesis
                                                                            2. aminoisobutyrate
                                                                              1. methyl malonyl-CoA
                                                                                1. succinyl-CoA
                                                                                  1. TCA cycle
                                                                              2. DPD
                                                                                1. initial/RLS
                                                                                  1. reduction of U or T
                                                                                    1. also degrades
                                                                                      1. 5-fluorouracil
                                                                                        1. tegafururacil
                                                                                  2. Functions of Nucleotides
                                                                                    1. precursors for DNA/RNA
                                                                                      1. metabolism
                                                                                        1. ATP/GTP
                                                                                          1. SAM, UDP sugar, CDP choline
                                                                                            1. cAMP/cGMP
                                                                                            2. coenzymes
                                                                                              1. NADH
                                                                                                1. FAD
                                                                                                  1. CoA
                                                                                                2. Disorders
                                                                                                  1. UMP synthase deficiency
                                                                                                    1. hereditary orotic aciduria
                                                                                                      1. function
                                                                                                        1. catalyze decarbox rxn
                                                                                                          1. orotate phosphoribosyltransferase
                                                                                                            1. orotidine-5'-monophosphate decarboxylase
                                                                                                          2. orotic acid accumulates
                                                                                                            1. megablastic anemia
                                                                                                              1. orotic crystalluria
                                                                                                                1. nephropathy
                                                                                                                  1. cardiac malformations
                                                                                                                    1. strabismus
                                                                                                                      1. recurrent infections
                                                                                                                      2. autosomal
                                                                                                                        1. recessive
                                                                                                                        2. dagnosis
                                                                                                                          1. enzyme assay
                                                                                                                            1. various tissues
                                                                                                                          2. treatment
                                                                                                                            1. oral uridine
                                                                                                                          3. DPD deficiency
                                                                                                                            1. autosomal
                                                                                                                              1. recessive
                                                                                                                              2. function
                                                                                                                                1. metabolism of uracil/thymine
                                                                                                                                2. develop severe toxicity
                                                                                                                                  1. when exposed to 5-FU
                                                                                                                                    1. chemotherapy drug
                                                                                                                                      1. also Xeloda
                                                                                                                                3. Drugs
                                                                                                                                  1. cancer treatment
                                                                                                                                    1. thymidine analog
                                                                                                                                      1. inhibition
                                                                                                                                        1. thymidylate synthase
                                                                                                                                        2. F replace CH3
                                                                                                                                          1. prevent DNA replication
                                                                                                                                        3. HIV
                                                                                                                                          1. derivatives of nucleosides
                                                                                                                                            1. AZT
                                                                                                                                              1. chronic use
                                                                                                                                                1. compromised mitos
                                                                                                                                              2. ddC, 3TC, ddI, d4T
                                                                                                                                                1. cellular kinase
                                                                                                                                                  1. triphosphate
                                                                                                                                                    1. metabolism
                                                                                                                                                      1. inhibition
                                                                                                                                                        1. HIV reverse transcriptase
                                                                                                                                                          1. chain termination
                                                                                                                                                            1. incorporate AZT or DDC
                                                                                                                                                              1. growing 3' end
                                                                                                                                                                1. truncate DNA chain
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