Quiz 4 chemistry Flashcards by Porter Koury

Exogenous substances that must be eliminated (xenobiotics)

toxins

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examples of exogenous toxins

microbial metabolites, man made chemicals

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Endogenous substances from digestion, energy, metabolism, tissue regeneration

toxins

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examples of endogenous toxins

ammonia

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toxins that can be absorbed through the skin, GI tract and lungs

exogenous toxins

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the process of transforming + removing harmful substances from the body

detoxification

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Phases of detox: heavy metals

sequestriation in soft stissues/bone –> mobilization and elimination

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Phases to detox: oxygen radicals

free radical quenching–> antioxidant cycling

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Phases of detox: ammonia

mobilization (glu/gln)—> conversion or direct elimination

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Phases of detox: organotoxins (non-polar)

redox reactions to introduce function groups –> conjugation reactions to assist mobilization and elimination

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phases of detox: organotoxins (polar)

conjugation and mobilization or direct elimination

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common clinical clues that point to toxic effects

(1) degeneration of hair, skin, nails, mucous membranes, and reproductive function (2) multiple chemical sensitivity or multisensory sensitivity.

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Hormesis model

biphasic responses to a substance.

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PCP

pesticides used as a wood preservative

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Phthalate esters

used in plastic wrap foods

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First priority when looking at detoxification

assessment of oxidation and NH3 status

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High 80HDG indicates

PUFA and DNA oxidative damage because the ability to neutralize free radicals has been exceeded

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NH3 rises from

processing of AA and intestinal bacterial metabolism

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urinary orotate, citrate, cis-aconitate, and isocitrate are markers for

hepatic/renal ammonia/nitrogen metabolism

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non-pola organix toxins are lipophilic and accumulate in

fat

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Frequent cite of toxin accumulation

ECM (extracellular matrix)

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metallothionein is a

metal binding protein

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metallothionein is abundant in

the kidneys where it sequesters essential elements to prevent them from spilling into the urine

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toxicity is

binding to critical sites of enzymes, DNA or transport/regulatory proteins

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low metallotionein levels may indicate

low toxic/nutrient metal intake or chronica inability to form this protein

High metallothionein may indicate

recent ingestion of zinc or other nutrients

methyl mercury accumulates in

astrocytes

Organotoxins

Xylene, phthalates

Organotoxins metabolism

promptly removed from body fluids, converted to derivatives and stored in fat

Organotoxins measurement in body fluids

only measures recent exposure

Xylene

most common organic solvenets released into the environmnet

High 2-methylhippurate indicates

xylene exposure b/c liver oxidizes and conjugates xylene to form methylhippurate

people have lower clearance of xylene when they

smoke and consume alcohol

esters of 1,2 benzenedicarboxyl acidwith alcohol that have 4-15 carbon atoms long

phthalates

phthalates are widely used in

plastic, cosmetics, other convenience items.

steroid hormone disrupters

phthalates

Increases felxibility in plastics

DEHP

MEOHP and MEHHP are sensitive biomarkers of

DEHP

Product of glycation

AGE

Cooking methods to reduce AGEs

1) cooking with moist heat 2) using shorter cooking temperatures 3) cooking at lower temperatures 4) use of acidic ingredients such as lemon juice or vinegar

Can cause vascular stiffening, oxidant stress, stimulate cytokines to produce inflammatory responses, some synthetic AGE-breaking compounds buy may present further risk of toxicity

AGE, ALES

RAGE

receptors of AGE, regulate physiological effects

____ can remove reactive carbonyl compounds before turned into AGE/ALES

Phase 1 and 11 detoxing

Activation of lysosome/proteasome degradation pathways can help remove

AGE/ALEs

Heme is required at the activation sites of emzymes (4)

oxygen binding, oxidizing systems, hemoglobin (protein myoglobin) cytochromes (like ETC and phase I detox)

A macrocylic, iron-sequestering molecule synthesized in most human tissues but primarily in the liver and bone marrow via the porphyrinogen pathway

heme

Porphyrins are ____porphyrinogens

oxidized, they have escaped from the pathway

The final phase of metal incorporation into protoporphyrin rings inserts

FE to create heme, Co to create cobalamin or MG to create chlorophyll in plants.

Porphyrinogen pathways involves __ enzymes

porphyrinogen pathway begins and ends in the

mitochondria

glycine + succinyl CoA--> ALA is step (1) requires

P5P - step 1

Formation of heme starts with... (where all-carbon molecules in heme come from)

glycine and succinyl CoA

ATP needed to create active ALA synthase

ALAS1 is formed in the

hepatic

ALAS2 is formed in the

bone marrow/erythroid tissue

Decreased iron intake will slow production of

ALAS2

Excessive heme production converts heme to hemin which blocks the activity of

ALAS1

5 beta-reduced steroid hormones stimulate synthesis of ala synthase to increase

heme synthesis

ALA + ALA -->

porphobilinogen

2 ALA molecules are condensed into porphobilinogen by

delta-ALA dehydratase

Zinc-containing enzyme located in cytosol, sensitive to lead that replaces zinc

D-ALA dehydratase

Uropophyrinogen III -> Coproporphyrinogen III occurs in the

cytosol

toxin that can lead to an accumulation of uroporphyrin III, heptacobyxyporphyrin, pentacarboxylporphyrin - intereferes with (UROD)

Arsenic

Interferes with the last decarboxylation reaction of UROD leading to accumulation of pentacarboxynporphrin

Mercury

CPOX can be impaired by

mercury and lead

Interference with CPOX leading to accumulation of coproporphyrin III

mercury and lead

Copropophyrinogen III enters the

mitochondria

Protoporphyrin IX accepts Fe2+ to form

Ferrous heme

formation of ferrous heme requires

ascorbic acid and cysteine as reductants

Enzyme for protoporphyrinogen IX-->protoporphyrin

PPOX- protophyrinogen oxidase

Cyclic compounds that bind metal ions, type of metalloprotein

porphyrins and porphyrinogens

are porphyrin precursors which are the colorless reduced forms of porphyrins

porphyrinogens

Cyclic molecules formed by the linkage of 4 pyrrole rings through methenyl bridges

porphyrin and porphyrinogen structure

Porphyria

purple color of porphyrins in the urine of some patients with defects in heme synthesis

All porphyrin are irreversible removed from the heme biosyntehsis pathway where they can accumulate as intermediate porphyrins of the corresponding name EXCEPT

Protoporphyrin IX

before Protoporphryin IX, the last before heme is

protoporphyrinogen IX

Worsened by low carb diets, meal skipping, alcohol, RX with sulfa, estroben, BCPs, toxins

porphyrias

Absence of heme leads to an increase synthesis of

ALAS and activity of ALAS

elevations of urinary penta, precopro and copro in autistic children may correlate with

mercury

heme transporter, regulates movement of copro III into mitrocondria

ABCB6

Less hemoglobin, less ability to oxygenate, less able to remove CO2 and less ability to carry H+

When porphyrins accumulate, it indicates

decreased ability to detoxify endogenous and exogenous toxins with less

cytochrome P450 enzymes

Quiz 4 chemistry Flashcards

(82 cards)