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Environmental Medicine > Biotransformation > Flashcards

Biotransformation Flashcards

1
Q

detoxification vs depuration?

A

detoxification: process of transforming a toxic substance into a non-toxic substance
depuration: action or process of freeing something of impurities; preferred term for the removal of xenobiotics by the body

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2
Q

what is a xenobiotic?

A

chemical compound that is foreign to the body or to an entire biological system
include: food additives, medications, pesticides, solvents, plastics, industrial products and byproducts

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3
Q

what is nasal fatigue?

A

don’t notice certain smell after being around it for a while

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4
Q

3 ways things are absorbed?

A

simple diffusion
passage through pores
specialized transport systems

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5
Q

what is facilitated diffusion is limited by what?

A

size of the pores

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6
Q

3 major sites of absorption?

A

GI tract: mostly in small intestine b/c greater surface area, longer transit time and more neutral pH than stomach (allows both weak acids and weak bases to be absorbed), also place of absorption of most nutrients
lungs
skin

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7
Q

there is effective absorption of what 3 things in the lungs?

A

gases
VOCs
small particulate matter

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8
Q

the skin is usu impenetrable unless what?

A

either the molecule is highly lipid soluble or the skin barrier is compromised

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9
Q

biotransformation and excretion of xenobiotics is dependent upon what?

A

concentration of the xenobiotic in the blood
some bound to plasma proteins, some moved to “storage sinks” like adipose
protein bound xenobiotics are not filtered through glomerulus therefore have a longer half-life

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10
Q

by putting a xenobiotic in a “storage sink” what are you changing?

A

changing the amount available for detox or excretion

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11
Q

what are 4 possible “storage sink” sites? and what accumulates in each usu?

A

liver
KD
adipose: pesticides
bones: aluminum, cadmium lead

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12
Q

barriers in our bodies that are meant to diminish the absorption of toxins? what do they exclude and what kind of substances do they let through easily?

A

blood brain barrier
placental barrier
both exclude water-soluble compounds but allow lipid-soluble compounds to easily pass through

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13
Q

what are 4 possible “storage sink” sites? and what accumulates in each usu?

A

liver
KD
adipose: pesticides
bones: aluminum, cadmium lead

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14
Q

barriers in our bodies that are meant to diminish the absorption of toxins? what do they exclude and what kind of substances do they let through easily?

A

blood brain barrier
placental barrier
both exclude water-soluble compounds but allow lipid-soluble compounds to easily pass through

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15
Q

what is biotransformation? what 2 paths can it lead to? typically the majority of xenobiotics under go what, what is the end-result?

A

biotransformation: metabolism can alter a substance dramatically leading to either detoxification and excretion OR bioactivation and toxicity
typically the majority of xenobiotics undergo metabolic changes to convert lipid soluble compounds into polar, water-soluble products to aid in excretion from the body

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16
Q

two phases of biotransformation?

A
  1. degradative= REDOX + hydrolysis + hydration + dehalogenation
  2. synthetic= metabolites from phase 1 are combined w/endogenous molecules and become less toxic and harmful and more water soluble: acetylation, acylation, sulfur conjugation, methylations, glucuronic acid conjugation, glutathione conjugation
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17
Q

what are CYP450s?

A

collection of enzymes that have been classified into families based on amino acid sequences; hemeproteins

18
Q

how are CYPs named? where are CYPs found?

A

family number followed by a subfamily letter

CYPs are found in endoplasmic reticulum of the liver, KDs, SI, lung and adrenal glands

19
Q

what can affect the levels of CYP 450 in the liver?

A

increased by administration of inducers (st. John’s Wort)

decreased by administration of inhibitors (grapefruit juice)

20
Q

how are CYPs named? where are CYPs found?

A

family number followed by a subfamily letter

CYPs are found in endoplasmic reticulum of the liver, KDs, SI, lung and adrenal glands

21
Q

what can affect the levels of CYP 450 in the liver?

A

increased by administration of inducers (st. John’s Wort)

decreased by administration of inhibitors like bupropion

22
Q

how does grapefruit juice act to inhibit CYPs?

A

contains furanocoumarins which cause a reduction in amount of CYP 3A4

23
Q

what are 4 other heavy metal inhibitors of CYPs?

A

organotins
cadmium
mercury
lead

24
Q

3 general “other” inhibitors?

A

trauma
obesity
LPS and inflammation

25
Q

CYP for PAHs? for benzene, styrene, xylene, toluene, ethers, TCE? major CYP in the liver and mostly responsible for oxidation of parathion and other OPs?

A

PAHs= CYP1A1
benzene, styrene, xylene, toluene, ethers, TCE= CYP2E1
predominant CYP in the liver, responsible for oxidation of parathion and OPs= CYP3A4

26
Q

what is phase 2 of biotransformation? what does it involve?

A

conjugation!
transformation of xenobiotics to polar compounds
usu products of phase 2 are more water soluble, more easily excretable and less toxic than parent compound or phase I metabolites
conjugation usu involves addition of an endogenous compound to a xenobiotic in 2 steps

27
Q

what is acylation? what does it use and require? enzymes needed are only found where?

A

acylation= adding an acyl group to a compound by acetyl Co-A with glycine, glutamine and taurine
bioavailability of a.a.s used in acylation come from endogenous and dietary sources
requires ATP
enzymes needed are only found in mitochondria in liver and KDs

28
Q

what does acetylation use and what does it require? chief degradation pathway for what compounds?

A

occurs via acetyl CoA using N-acetyl transferase found in the liver
needs B5 to function

29
Q

what is acylation? what does it use and require? enzymes needed are only found where?

A

acylation= adding an acyl group to a compound by acetyl Co-A with glycine, glutamine and taurine
bioavailability of a.a.s used in acylation come from endogenous and dietary sources
requires ATP
enzymes needed are only found in mitochondria in liver and KDs

30
Q

what does sulfonation need to happen?

A

needs a supply or inorganiic sulfate, vit A, niacin

31
Q

2 types of sulfur conjugation?

A

sulfonation and glutathione conjugation

32
Q

what causes GSH deficiency?

A

heavy metal presence b/c replenishment of the GSH cannot occur

33
Q

3 primary routes of excretion?

A

urinary
biliary
pulmonary

34
Q

what is methylation?

A

donation of a methyl group to a substrate

35
Q

3 primary routes of excretion?

A

urinary
biliary
pulmonary

36
Q

what part of the glomerulus contains CYP enzymes? what can this cause? where can cadmium and lead be reabsorbed and stored?

A

proximal tubules contain CYP enzymes which can cause metabolism of some xenobiotics
proximal tubules is also the site of cadmium and lead reabsorption

37
Q

what kind of molecule is too big to be filtered through the glomerulii?

A

compounds that are bound to plasma proteins are too large to be filtered through glomerulii

38
Q

what part of the glomerulus contains CYP enzymes? what can this cause? where can cadmium and lead be reabsorbed and stored?

A

proximal tubules contain CYP enzymes which can cause metabolism of some xenobiotics
proximal tubules is also the site of cadmium and lead reabsorption

39
Q

what does biliary excretion depend upon?

A

depends on concentration of xenobiotic in the liver
rate at which a compound is excreted through feces is dependent on how long it takes for the compound to be reabsorbed in the process of excretion

40
Q

what can excretion through the feces of a xenobiotic be affected by?

A

can be affected by bowel transit time
cholestasis
leaky gut
rate of hydrolysis of conjugates by intestinal bacteria

Environmental Medicine (9 decks)

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