11 Flashcards

1
Q

What is nitrogen balance

A

anything we consume in excess of our needs is broken down and excreted
(because our bodies can’t store protein)

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2
Q

Where does nitrogen come from in our body

A

amino acids (contain CHON)
- only source from our diets

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3
Q

When are the CHON of aa metabolized

A

when there is excess protein or not enough carbs

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4
Q

In what form is nitrogen after being broken down as amino acids
Why is it a problem

A

ammonia (NH3)
has a pKa of 9.3 (but blood pH is 7.35-7.45)
when forming ammonium –> toxic for our bodies (must be removed as urea)

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5
Q

How to take nitrogen off of amino acids

A

transamination –> transfer nitrogen between aa

deamination –> remove amino group (generates free ammonium)
- generates energy

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6
Q

What is transanimation

A

transfers nitrogen from one molecule to another

allows tissues to use the leftover carbon skeleton for something eelse (energy metabolism)

allows cells to produce non-essential aa

a-ketoglutarate/glutamate is the most common acceptor of amino group

PLP pyridoxal phosphate = coenzyme required for these reactions and is the active form of vit B

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7
Q

What is deanimation

A

removes a nitrogen from a molecule but generates nitrogenous waste (NH3/NH4+)

cells can use the leftover carbon skeleton for something else

NH3/NH4+ is toxic and must be removed
- reversible reaction
- too much NH4+ = reaction will reverse, using up all the a-ketoglutarate in the mitochondria
(a-keto depleted – needed for TCA cycle, glutamate builds up, glutamate and glutamine build up in the cell – shift in osmotic balance causing cells to swell)

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8
Q

How is ammonium transported through the body

A

as urea
as aa (glutamine and alamine) – non toxic polar molecules

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9
Q

Why can alanine travel through the blood

A

non toxic and polar
- can freely travel in the blood

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10
Q

What does alanine do with ammonium

A

tissues release excess nitrogen as alanine into the blood

circulates to liver

liver alanine undergoes transanimation – converts it to pyruvate and transfers the nitrogen to glutamate

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11
Q

What happens to the glutamate made aar of transanimation

A

glutamate can be deanimated to release the nitrogen as NH4+
- can be packaged into urea

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12
Q

How does glutamate transport nitrogen

A

glutamate (in muscle) undergoes transanimation and transforms into glutamine

glutamine goes to liver and kidneys to be deanimated and secrete ammonium

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12
Q

how is nitrogen excreted

A

liver packages into urea and it goes to blood where it is excreted

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12
Q

What does high levels of ammonium mean

A

problem with the liver
(only site of urea pakcaging)

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13
Q

what does high levels of urea mean

A

problem with the kidneys
(only site of urea excretion)

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14
Q

What is the urea cycle

A

multistep cycle that takes place inthe livr

enzymatic process where packages and move extra nitrogen into urea
- relies on transanimation and aa metabolism

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15
Q

Describe the urea cycle , what does it start with

A

mitochondria

CO2 from TCA cycle and water –> forms bicarbonate
joins with amonium to form phospahte

transanimation
forms amino acid
becomes another amino acid
and another amino acid
eventually becomes urea

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16
Q

What are reactive oxygen species

A

oxygen is biradical (likes ot form two bonds for full valence electrons –> in seperate areas)
therefore oxygen is not very reactive

However, when oxygen gets another electron, it becomes very reactive
*can be a problem in the body as it pulls things away

17
Q

What are transition states

A

molecules with extra electrons (radicals) – but trapped in enzymes

18
Q

When are free radicals dangerous

A

when not in enzyme
Will steal electrons from other molecules and causes other molecules to be come reactive (chain reaction of damage)

19
Q

What are sources of reactive oxygen species

A

Electron transport chain
- transfers electrons between carriers and complexes until it eventually reaches oxygen

Ionizing radiaiton
- water or skin

drug metabolism
- cytochrome P450 enzymes metabolize drugs (including alcohol) and chemical toxins
- oxidize the drugs and other substance sot make them more solubel for excretion
- leaky enyzmes where radicals can escape and become free radicals

Inflammation
- ROS are used to destroy invading pathogesn or clean up dad cells in damaged tissues
- activated neutrophils “respiratory burst” consumes oxygen to create reactive substnaces that will kill phagocytosed bacteria
- release of free radicals in areas of inflmmation can lead to damage in surrounding tissues

20
Q

What are the species of free radicals

A

Reactive oxygen species
Nitrogen oxygen species

21
Q

What are reactive ntirogen-oxygen species
What causes

A

free radicals and can cause damage

sources:
- nitrates from diets or bacteria produced from intestine
- smoking/pollution/smog

22
Q

What happens in ROS damage

A

free radical “pulls” an electron from a molecule, turning that molecule into a radical, which in turns pulls another electron from anoter molecule, turning that into a free radical

23
Q

What are specific damages of ROS

A

DNA damage
- strand breaks
- 1 of 20 different alterations that can lead to mutations
- guanine converted to 8-hydroxyguanine can form bonds with both A and C (G-C pair may be replicated as a T-A pair – creates mutation)

24
Q

What are the cellular defnese mechanisms

A

enzymes that neutralize radicals
antiocidants that donate electrosn to radicals but dont become radicalas themselves

25
Q

What are protective enzymes

A

ex. superoxide dismutases (SOD) and catalses have different isoforms that exist in defferent parts of the cell

Glutathione (tripeptide) peroxidases function to remove hydrogen peroxide formed outside of peroxisomes

26
Q

what are antioxidants

A

donate electrons

  • vitamins :
    Vit E – donate electron to radicals (fat-soluble) and C — donate elctron to vit E(water-solubule)
27
Q

What is a non-communicable disease (NCD)

A

when it is not transmissible between individuals

bio and gentical factors

canceer, CD, RD, diabetes

largely preventable

28
Q

How does alcohol impact the brain and CNS

A

impair judgment (frontal lobe) – psychoactive agent

speech and vision centres

hand-eye coordination and voluntary muscle function

heart and respiration

29
Q

Describe ehtanol

A

lipid and water-soluble, very easily absorbed and transported

metabolized primarily by the alcohol dehydrongenase (ADH) enzyme in the cytosol of the liver

30
Q

When does acetalaldehyde form

A

product of alcohol metabolism and is TOXIC

31
Q

What does acetaldehyde dehydrodenase do

A

converts acetaldehyde (toxic) to non-toxic acetate which can be used by muscle and other tissues as fuel
– converted to acetyl CoA

32
Q

What does alcohol metabolism produce

A

up to 5 NADHs and 1 FADH2

33
Q

What are NADHs used for

A

generate 17 ATP (2 are used to make Acetyl-CoA)

net gain of 15 ATP

34
Q

What is the microsomal ehtanol oxidizing system (MEOS)

A

inducible (depends on alcohol consumption)

Part of the cytochrome P450 system of enzymes

enzymes are embedded in the membrane of the endoplasmic reticulum

35
Q

When is the MEOS system used

A

high levels of alcohol consumed

cytochrome P450 enzymes are responsible for drug metabolism and are “leaky”

free radicals are generated from MEOS causing oxidative stress

36
Q

What happens when alcohol and tylenol is mixed

A

tylenol (acetaminophen) normally metabolized in the liver and excreted in the kidney

but after alcohol, C P450 enzyme that is part of MEOS gets expressed at high level

this enzyme can turn Tylenol into a toxin

37
Q

Why are people who consume alcohol more likely to overdose

A

alcohol can compete with the medication for cytochome P450 enzymes, decreasing tis metabolism and excretion
- increasing its dose

38
Q

What happens to the CYP enzymes of people who consume excess alcohol on a regular basis

A

CYP enzymes always expressed, changing the way they metabolize drugs

39
Q

Why is excess NADH/NAD+ in the liver bad (after alcohol metabolism)

A

ETC and TCA shut down because excess NADH signals surplus of energy

but no surplus

shift in metabolism, leading to pyruvate to be converted to lactate (lactic acidosis)

40
Q

What is steatotic liver diseases (fatty liver)
What will happen AAR

A

fat deposits (steatosis) can be seen in the liver after one episode of binge drinking

metabolic dysfunction-associate steatotic liver disease (MASLD)

alcohol-associated liver disease

41
Q

What would happen as a result of excessive excessive drinking

A

produce more MEOS enzymes (increased gene expression) but even these can’t keep up with the quantity of alcohol they have consumes