Metabolizace, degradace a vylučování vitamínu C

Jaterní metabolizace vit. C

• Zčásti je přeměněn na inaktivní sloučeniny
• Vylučují se močí

Renální vylučování

• Under steady state conditions
• Intakes rise from around 100 mg/day increase in urinary output of vit. C
• At 1000 mg/day almost all absorbed vitamin C is excreted [4]

Nezměněný vit. C

• Renální eliminační práh 14 µg/ml [1] 1.4 mg/dL or higher [12]
• Po překročení je vic. C vylučován v nezměněný močí (DiPiro, 2001)[1]

Oxalát

• Aktivní metabolic vit. C Dehydroaskorbát postupně degradován na oxalát
• Vylučován ledvinami - riziko krystalizace a vzniku oxalátové nefropatie při podání vysokých dávek !!!
• I.v. podání vyšších dávek jen pacientům s neporušenou funkcí ledvin
• Do 24 h po i.v. podání askorbátu návrat hladin do normy [1]

Renal-tubular reabsorption

• Retains vitamin C in the tissues
• Up to a whole body content of ascorbate
• About 20 mg/kg body weight [4]
• During times of low dietary intake
• vitamin C is reabsorbed by the kidneys rather than excreted [12]

Recycling mechanisms of vit. C

• Prevent the loss of intracellular concentrations of ascorbate and other antioxidant molecules
• Formed by exogenous antioxidants and the endogenous antioxidant system.
• Many of them can be altered in a chronic oxidative stress state
• Making it more difficult to maintain normal ascorbate concentrations
• Increasing the requirements for vitamin C in some subjects [11]

Ascorbyl radical

• Relatively stable molecule
• Average life of 10–5 s
• Low reactivity
• Ability of the unpaired electron to resonate between carbons 1' and 3' without interacting with O2 [11]
• Ascorbyl radical is formed in the plasma membrane
• By the reduction of alpha-tocopherol [11]
• Vitamin C to an oxidized state
• Semidehydroascorbic acid
• Dehydroascorbic acid

Two ascorbyl radicals

• Can react with each other
• Dismutation reaction
• One molecule is reduced to ascorbate
• Other is oxidized to DHA [11]

Reduction of the ascorbyl radical

• NADH-dependent system
• Mediated by the ascorbyl free radical reductase (AFR reductase)
• Located in the cell membrane
• Two types of AFR reductases:
• Transmembrane
• In the inner membrane [11]

Thioredoxins

• Cellular proteins
• Catalyze the reduction of disulphides in different enzymes
• Ribonucleotide reductase
• Through the transfer of an electron from their thiol group [11]

• Thioredoxin reductase

• Enzyme responsible for keeping thioredoxin in its reduced form
• Ability of this enzyme to recycle DHA and ascorbyl radical into ascorbate
• By an NADPH-dependent process in cytosol [11]

Glutathione

• Capable of reducing DHA to ascorbate [11]

Dihydrolipoic acid

• Capable of reducing DHA to ascorbate
• Can also reduce the ascorbyl radical [11]

Ascorbic acid converts (reversibly) to dehydroascorbate (DHA)

• From that compound non-reversibly to 2,3-diketogluonate and then oxalate
• These three compounds are also excreted via urine [12]

• Takže oxalátová nefropatie více hrozí u stavů spojených s deplecí glutathionu nebo při blokádě recyklujících enyzmů nebo masivní oxidaci i.v. podaného vitamínu C, která přehltí systém recyklace

• Dokážu si tedy představit, že předchozí podání acetylcysteinu je nefroprotektivní, podobně jako krácte po infuzi podaný glutathion

Koenzymy

• During the biochemical processing of high doses of intravenous ascorbate
• Cycling of glutathione peroxidase and glutathione reductase (GSH-GSSG redox cycle) is increased
• Increase in GSH-GSSG cycling utilizes:
• NAD
• FAD
• selenium
• magnesium
• Other nutrients [13]