FIGURE 14-20 General scheme of the pentose phosphate pathway FIGURE 14-20 General scheme of the pentose phosphate pathway. NADPH formed in the oxidative phase is used to reduce glutathione, GSSG (see Box 14-4) and to support reductive biosynthesis. The other product of the oxidative phase is ribose 5-phosphate, which serves as a precursor for nucleotides, coenzymes, and nucleic acids. In cells that are not using ribose 5-phosphate for biosynthesis, the nonoxidative phase recycles six molecules of the pentose into five molecules of the hexose glucose 6-phosphate, allowing continued production of NADPH and converting glucose 6-phosphate (in six cycles) to CO2.

FIGURE 14-21 (part 1) Oxidative reactions of the pentose phosphate pathway. The end products are ribose 5-phosphate, CO2, and NADPH.

FIGURE 14-21 (part 2) Oxidative reactions of the pentose phosphate pathway. The end products are ribose 5-phosphate, CO2, and NADPH.

FIGURE 14-21 (part 3) Oxidative reactions of the pentose phosphate pathway. The end products are ribose 5-phosphate, CO2, and NADPH.

FIGURE 14-21 (part 4) Oxidative reactions of the pentose phosphate pathway. The end products are ribose 5-phosphate, CO2, and NADPH.

FIGURE 14-21 Oxidative reactions of the pentose phosphate pathway FIGURE 14-21 Oxidative reactions of the pentose phosphate pathway. The end products are ribose 5-phosphate, CO2, and NADPH.

Fase non ossidativa C5 + C5 <___> C3 + C7 ____________________________ 3 C5 <___> 2 C6 + C3

FIGURE 14-23b The first reaction catalyzed by transketolase FIGURE 14-23b The first reaction catalyzed by transketolase. (b) Conversion of two pentose phosphates to a triose phosphate and a seven-carbon sugar phosphate, sedoheptulose 7-phosphate.

FIGURE 14-23a The first reaction catalyzed by transketolase FIGURE 14-23a The first reaction catalyzed by transketolase. (a) The general reaction catalyzed by transketolase is the transfer of a two-carbon group, carried temporarily on enzyme-bound TPP, from a ketose donor to an aldose acceptor.

FIGURE 14-24 The reaction catalyzed by transaldolase.

FIGURE 14-25 The second reaction catalyzed by transketolase.

Richiesta di ribosio 5-fosfato ma non di NADPH 5 glucosio 6-fosfato + ATP ___> 6 ribosio 5-fosfato + ADP + 2H+

Richiesta bilanciata di ribosio 5-fosfato e NADPH glucosio 6-fosfato + 2 NADP+ + H2O ___> ribosio 5-fosfato + 2 NADPH + CO2 + 2H+

Richiesta di NADPH ma non ribosio 5-fosfato Fosfoglucosio isomerasi Fruttosio 1,6 bisfosfatasi Aldolasi 6 glucosio 6-fosfato + 12 NADP+ + 6 H2O ___> 6 ribosio 5-fosfato + 12 NADPH + 12 H+ + 6 CO2 6 ribosio 5-fosfato ___> 4 fruttosio 6-fosfato + 2 G3P 4 fruttosio 6-fosfato + 2 gliceraldeide 3-fosfato ___> 5 glucosio 6-fosfato + fosfato _________________________________________________________________________ Glucosio 6-fosfato + 12 NADP+ + 7 H2O ___> 6 CO2 + 12 NADPH + 12 H+ + fosfato

Richiesta di NADPH e energia ma non di ribosio 5-fosfato 3 glucosio 6-fosfato + 6 NADP+ + 5 NAD+ + 5 Pi + 8 ADP ___> 5 piruvato + 3 CO2 + 6 NADPH + 5 NADH + 8 ATP + 2 H2O + 8 H+

FIGURE 14-27 Role of NADPH in regulating the partitioning of glucose 6-phosphate between glycolysis and the pentose phosphate pathway. When NADPH is forming faster than it is being used for biosynthesis and glutathione reduction (see Figure 14-20), [NADPH] rises and inhibits the first enzyme in the pentose phosphate pathway. As a result, more glucose 6-phosphate is available for glycolysis.

ROS (Reactive Oxygen Species) *

ROS (Reactive Oxygen Species) Il superossido può derivare dalla respirazione mitocondriale (complessi I e III) o dall’attività di enzimi (ad es., xantina ossidasi) Perossido di idrogeno Radicale idrossile

Formazione di H2O2 nei perossisomi: degradazione dei D-amminoacidi Degradazione nei perossisomi degli acidi grassi a catena molto lunga porta a formazione di H2O2

Formazione del radicale idrossile Reazione di Haber-Weiss: Fe3+ + •O2− → Fe2+ + O2 Il secondo passaggio è la reazione di Fenton: Fe2+ + H2O2 → Fe3+ + OH− + •OH Reazione netta: •O2− + H2O2 → •OH + OH− + O2

Reazione della catalasi (Km elevata): Detossificazione ROS O2 + e- → O2−• + e- + 2H+→ H2O2 Reazione della SOD: 2O2−• + 2H + → H2O2 + O2 Reazione della catalasi (Km elevata): 2H2O2 → 2H2O + O2 Il superossido può derivare dalla respirazione mitocondriale (complessi I e III) o dall’attività di enzimi (ad es., xantina ossidasi)

Superossido dismutasi (Mn nei mitocondri; Cu/Zn nel citoplasma)

CATALASI 2 H2O2 → 2 H2O + O2

EFFETTI DANNOSI DEI ROS Danno al DNA (mutagenesi) Ossidazione di acidi grassi polinsaturi nei lipidi (perossidazione lipidica) Ossidazione di amminoacidi in proteine Inattivazione ossidativa di specifici enzimi via ossidazione di cofattori

MECCANISMO DI PEROSSIDAZIONE LIPIDICA

Glutatione (GSH)

GSSG + NADPH + H+ → 2 GSH + NADP+ Reazione del GSH con i perossidi Glutation perossidasi (Km bassa): 2 GSH + RO—OH → GSSG + H2O + ROH Glutation reduttasi: GSSG + NADPH + H+ → 2 GSH + NADP+

Glutathione Peroxidase

SELENOCISTEINA (codificata da uno speciale codone UGA)

Ciclo del Glutatione

BOX 14-4 FIGURE 1 Role of NADPH and glutathione in protecting cells against highly reactive oxygen derivatives. Reduced glutathione (GSH) protects the cell by destroying hydrogen peroxide and hydroxyl free radicals. Regeneration of GSH from its oxidized form (GSSG) requires the NADPH produced in the glucose 6-phosphate dehydrogenase reaction.

Vicia faba

DIVICINA (glicoside da Vicia faba)

Sulfanilamide Pamachina

Eritrociti con corpi di Heinz

Vitamina E (a-tocoferolo) Fonti: oli vegetali, noci, cacao … RDA: 15 mg

Vitamina C (acido ascorbico) ascorbato deidroascorbato semi-deidroascorbato Fonti: vegetali a foglia verde, agrumi, pomodori, kiwi …. RDA: 30 - 60 mg