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Phase 1 Flashcards > Liver fat metabolism and storage organ > Flashcards

Liver fat metabolism and storage organ Flashcards

1
Q

Most of the body’s fat is stored where? Some is stored where?

A

In adipocytes which form adipose tissue

In hepatocytes

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2
Q

What % of dietary lipids are triglycerides? What happens to cholesterol removed from the blood and tissue by HDLs?

A

95%

They deliver this cholesterol to the liver which secretes it into the bile/ converts it into bile salts

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3
Q

Why is LDL essential in supplying cells with the cholesterol they require?

A

It is used to synthesise cell membranes and for steroid hormone production in the gonads and adrenal glands and aldosterone and cortisol

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4
Q

What does VLDL do?

A

Synthesised in hepatocytes and it carries triglycerides from glucose in liver to adipocytes.

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5
Q

Where is most adipose tissue found? Function of adipocytes?

A

In deposits underlying the skin/ surrounding internal organs.
Make and store triglycerides during periods of food uptake- when food not being absorbed from SI, releases fatty acids and glycerol into the blood for use by other cells to provide energy for ATP formation.

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6
Q

How are fatty acids catabolised in the mitochondria?

A

1) CoA is linked to carboxyl at end of fatty acid
2) ATP is broken down into AMP and 2Pi
3) CoA derivative proceeds through B-oxidation reactions
4) Acetyl CoA splits off from fatty acid and two pairs of H atoms are transferred to FAD and NAD+
5) H atoms enter oxidative phosphorylation
6) CoA attaches to fatty acid and cycle repeats.

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7
Q

What does lipoprotein lipase hydrolyse triglycerides into? What does hepatic lipase do?

A 
Within lipoproteins into 2 free fatty acids and 1 glycerol molecule. 
Converts IDL (intermediate density lipoprotein) into LDL- packages it with more triglycerides to be released in the body.
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8
Q

Iron is used in what 3 things? Homeostatic control of iron balance resides primarily where? How much ingested iron is normally absorbed?

A

Haemoglobin, myoglobin and bone marrow.
In intestinal epithelium in duodenum- actively absorbs iron
Only a small fraction (10%)

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9
Q

What acts as an intracellular store for iron? Where does most iron bound to ferritin in the intestinal epithelial cells go?

A

Ferritin

Released back into the intestinal lumen when cells at tips of villi disintegrate- iron then excreted in faeces.

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10
Q

What happens when the bodies stores of iron are enough? When body stores are low?

A

Increased transcription of gene encoding for ferritin- reduced iron in blood
Production of intestinal ferritin decreases, decreasing amount of iron bound to ferritin

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11
Q

Where does the absorbed iron that doesn’t bind to ferritin go? Where does it go?

A

Released into blood where it can circulate bound to plasma protein transferrin
To bone marrow to be incorporated into new erythrocytes

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12
Q

Where is most iron stored? %s of where iron is stored?

A

In liver ferritin within Kupffer cells.

50% in haemoglobin, 25% in heme containing proteins, 25% is in liver ferritin

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13
Q

What 3 proteins are made by the liver? Most abundant plasma protein?
Functions of albumin?

A

Plasma proteins, clotting factors and complement factors
Albumin
Binding and transport of large hydrophobic compounds like bilirubin, fatty acids, hormones and drugs (NSAIDs and warfarin)

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14
Q

What is colloid osmotic pressure? How does albumin maintain osmotic pressure?

A

Effective osmotic pressure across blood vessel walls which are permeable to electrolytes but not large molecules.
Water conc in plasma is slightly lower than that of interstitial fluid, so water moves out of the interstitial fluid back into blood plasma

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15
Q

What are the opposing forces that act to move fluid across the capillary wall? What are the 4 forces?

A

Starling Forces
Capillary hydrostatic pressure- favours movement out of capillary
Interstitial hydrostatic pressure- movement in
Osmotic force due to plasma protein- movement in
Osmotic force due to intestinal fluid protein conc- movement out

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16
Q

Where does interstitial move in and out of the capillaries? What happens to albumin levels during liver failure?

A

Out at arterial end of capillaries and in at venous end of capillaries
Hypoalbuminaemia- decrease in oncotic pressure– oedema

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17
Q

Why else can albumin reduce?

A

Nephrotic syndrome- increased glomerular permeability, haemorrhage, gut loss and burns

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18
Q

Antibodies are mostly what globulin type? Not made in what organ? Some are what globulin types made in the liver?

A

Gamma-globulins
Not made in liver
Alpha/ beta globulins

19
Q

Globulins involved in blood transport of what 3 things?

A

Lipids by lipoproteins, iron by transferrin and copper by caeruloplasmin

20
Q

The liver produces all clotting factors except what 2? Liver also produces what needed for Vitamin K absorption? Vitamin K needed for synthesis of what clotting factors?

A

Calcium (IV) and von Willebrand factor (VIII)
Bile salts
10, 9, 7, 2 (1972)

21
Q

What do complement factors do?

A

They play an important role in the immune response to pathogens- plasma protein which sticks to pathogens. Recognised by neutrophils- helps mark pathogens to kill

22
Q

What are xenobiotics? Can be absorbed across where? Example? Excreted in what?

A

Foreign chemical substances not normally found/ produced in body which cannot be used for energy requirements.
Across lungs, skin or ingested e.g. drugs
In bile, urine, sweat and breath

23
Q

What features do pharmacologically active compounds have?

A

Lipophilic- so can pass through plasma membranes to reach metabolising enzymes
Non-ionised at pH 7. 4
Bound to plasma proteins to be transported in blood

24
Q

What is a microsome?

A

Small particle consisting of a piece of endoplasmic reticulum to which ribosomes are attached, so microsomal enzymes are enzymes which can be found in these microsomes.

25
Q

What enzyme types can be found in Phase 1 and Phase 2 reactions? What reactions are microsomal enzymes involved in?

A

Both microsomal and non-microsomal enzymes

Mainly Phase 1 reactions, but can do Phase 2

26
Q

Where are microsomal enzymes found? Example?

A

On SER, mostly in liver hepatocytes but in kidneys and lungs too.
Cytochrome P450

27
Q

What occurs during Phase 1 reactions? During Phase 2 reactions? Activity can be induced/ inhibited by? Involved in what reactions types?

A

Biotransform substances
Glucuronidation- addition of glucuronic acid
Drugs, food, age, bacteria and alcohol
Oxidative, reductive and hydrolytic reactions

28
Q

Non-microsomal enzymes involved mainly in what reactions? Located where? What feature do they have?

A

Phase II reactions
In cytoplasm and mitochondria of hepatocytes in liver but in other tissue too
Non-specific- involved in Phase 1 and Phase 2 reactions

29
Q

Non-microsomal enzymes involved in all conjugation reactions except from what? Examples?

A

Glucoronidation

Protein oxidases, alcohol and aldehyde dehydrogenase, conjugases

30
Q

Most drugs are excreted by what organ? Lipophilic drugs not effectively removed why? Aim of drug metabolism?

A

Kidneys
Passively absorbed as they can diffuse through cell membranes easily.
Make drugs more polar- cannot cross membranes and easily excreted

31
Q

What does Phase 1 reaction aim to do?

A

Make the drug more hydrophilic so that it can be excreted by kidneys
By adding hydroxyl group to drug/ other reactive sites can be used for conjugation reactions (Phase II reactions)

32
Q

Examples of non-synthetic catabolic reactions? What does functionalisation involved?

A

Oxidation, reduction and hydrolysis
Introduces reactive group to drug e.g. OH, SH, NH2, COOH
Product usually more reactive and small increase in hydrophilicity

33
Q

Cytochrome P450 type of what enzyme? Involved in what reactions? Uses what group to oxidise substances? Products are usually what soluble?

A

Microsomal enzyme
Phase I reactions
Uses heme group to oxidise substances
More water soluble

34
Q

Cytochrome P450 enzymes large family with what prefix? Known as what? 1st number means what? Letter means what? 2nd number means what?

A 
CYP
Isoforms/ isozymes 
Family belongs to 
Indicates subfamily 
Individual genes involved
35
Q

What is cytochrome P450 reductase needed for? Contains flavoprotein which in turn consists of what 2 things? FAD does what? FMN does what?

A

Needed to transfer electrons from NADPH to CY P450
Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)
Accept electrons from NADPH
Electron donor to CYPs

36
Q

Overall reaction of NADPH reduction?

A

NADPH + H+ + O2 + RH– NADP + H2O + ROH

37
Q

Phase 1 reactions can do what 4 things?

A

Inactivate drugs, further activate drugs, activate drug from pro-drug and make a drug into a reactive intermediate.

38
Q

Phase 2 reactions are what reaction types? Examples? Donor compound in glucuronidation? Other examples?

A

Synthetic anabolic e.g. glucuronidation
UDPGA
Sulfation, amino acid conjugation, acetylation, methylation and H2O conjugation

39
Q

What is involved in conjugation reactions?

A

Attachment of substituent groups, usually inactive products, catalysed by transferases and significantly increases hydrophilicity for renal excretion.

40
Q

Glucuronidation involves adding what group? Done by what enzyme? Coenzyme also involved? Substances arising from this process? Forms what bonds?

A 
Glucuronic acid 
Glucuronosyltransferase microsomal enzyme
UDPGA
Glucuronides 
Covalent bonds
41
Q

Features of aspirin? Irreversibly inhibits what? Aspirin+ water forms what? Conjugated with what? Forms a range of what metabolite type?

A 
Analgesic (pain relief,) NSAID, anti platelet, pro-drug
Cyclooxygenase (COX)
Salicylic acid and ethanoic acid
Glucuronic acid
Ionised
42
Q

What is paracetamol also known as what? Has what two features? Conjugated with what in Phase II reaction? What happens if stores of glucuronic acid and sulphate are running low? Treated with what?

A

Acetaminophen
Pain relief (analgesic) and antipyretic agent (lowers body temperature)
Glucuronic acid and sulphate
Undergoes Phase I metabolism via oxidation to produce toxic NAPQI- removed by conjugation with glutathione (can run low in overdoses)
N-acetyl cysteine

43
Q

Ethanol is converted into acetylaldehyde using what? This is converted into acetate using what? This is converted into what 2 products? Acetylaldehyde is what? Signs of high levels?

A 
Alcohol dehydrogenase
Aldehyde dehydrogenase 
CO2 and H2O 
Carcinogenic 
Facial flushing, rapid heartbeat and nausea

Phase 1 Flashcards (35 decks)

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