biochemistry Flashcards

1
Q

what is classified as binge drinking

A

drinking more than 10 standard drinks in one sitting

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2
Q

how does alcohol lead to dehydration

A

interferes with pituitary gland production of ADH which would normally promote aldosterone production –> therefore loss of water and salt through urine

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3
Q

what are the fates of the oxygen free radicals that can be created using the p450 system

A

can either drift off and destroy the membrane of the ER or the DNA, or can bind to the substrate

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4
Q

what is haemosiderin

A

polymer of ferritin

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5
Q

what is function of the Standard Ames Assay

A

to check whether chemicals are mutagenic or not

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6
Q

treatment of Crigler-Najjar syndrome

A
  • phototherapy (10-12 hours per day)
  • liver transplant
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6
Q

what are the types of alcohol induced liver damage

A
  • fatty liver
  • alcoholic hepatitis
  • alcoholic cirrhosis
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6
Q

how much of the bile salts are reabsorbed

A

95%

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7
Q

what is the function of haptoglobin

A
  • binds to the Hb that is released from RBCs when they are haemolysed at sites remote from the spleen
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8
Q

what holds the Fe2+ in p450

A

a cysteine anchor forms a ligand to the Fe in Haem

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9
Q

what is a microsome

A

artefact of breaking SER

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10
Q

what is the mainstay detoxification method of p450

A

adds an OH group to chemicals to make them soluble and then addition of a sugar to make them even more soluble

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10
Q

where is the active site on p450

A

right next to the Haem group

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11
Q

regions of the brain that are affected when drinking alcohol (in order) and what does this do

A

cerebral cortex - impaired judgement and info processing

forebrain - memory and emotions

cerebellum - balance and movement

brainstem - breathing and circulation

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12
Q

function of Fe in p450

A

alternates between 2+ and 3+ as electrons are donated to oxygen

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12
Q

what are the two pathways for benzopyrene

A
  • undergoes phase one and two reactions to become a kidney safe product
  • undergoes different phase 1 reaction which then goes through p450 –> carcinogen
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12
Q

dioxin is p450 dependent or independent to become mutagenic

A

independent - mutagenic without p450

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12
Q

what is the colour change and the causes of the colour change of bruises

A
  • initial: reddish as blood traped in interstitial tissue - 1-2 days: blue-purple (deoxy Hb and metHb) - 5-10 days: green/yellow (biliverdin) - 10-14 days: yellow/brown (bilirubin)
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13
Q

what causes Gilberts disease

A

decreased conjugation of bilirubin and decreased uptake in some cases

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14
Q

what is the main p450 involved in the metabolism of prescription drugs

A

CYP2D6

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15
Q

what two levels in the serum will show pancreatitis

A

serum amylase and/or serum lipase elevated

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17
Q

what is the correlation between p450 and steroid synthesis

A

lots of families of p450s are involved in conversions of steroid hormone synthesis

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18
Q

how do you get dioxin in the environment

A

by-product of chlorine bleaching of paper pulp, incerating waste plastic and pesticide/herbicide manufacture

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19
Q

what causes gall stones

A

too much free cholesterol in the bile –> precipitates as crystals = gall stones

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20
Q

which p450 enzyme is induced with dioxin

A

CYP1A1

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20
Q

what is the number of drinks for high risk to health per day

A

6+ males 4+ women

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21
Q

how can alcohol lead to hypoglycaemia

A

alcohol dehydrogenase converting alcohol to acetaldehyde produces NADH. High NADP represses gluconeogensis –> hypoglycaemia

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22
Q

action of phenobarbitol

A

acts directly on DNA to turn on response elements than turn on 2B2 and 3A1 genes that upregulate the activity of p450 50-100x

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23
Q

what does conjugation of bilirubin mean

A

adds sugars to it to make it more soluble

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23
Q

what two hormone are involved in the regulation of pancreatic juice release

A

CCK and secretin

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24
Q

where is bilirubin produced

A

in the spleen (usually) as a breakdown product of RBCs

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24
Q

what are bile salts made of

A

cholesterol derivitive with a carboxylic acid group - commonly amide linked to glycine or taurine to increase solubility

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25
Q

what happens to the alcohol metabolism with sustained alcohol intake

A

CYP2E1 induced to high levels and provides an alternative pathway = microomal ethanol oxidising system

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25
Q

how much alcohol is cleared per hour

A

0.015%

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26
Q

what equation does p450 typically catalyse

A

RH + NADPH + H+ + O2 ——-> ROH + H20 + NADP+

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27
Q

how does phototherapy treat Crigler-Najjar syndrom

A

some of the souble bonds in bilirubin isomerize cis/trans bonds from Z to E configuration ==> more soluble

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29
Q

what are the 2 most commonly known carcinogens that result due to p450

A
  • benzopyrene
  • aflatoxin
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30
Q

what positive health benefits does drinking a moderate amount of alcohol do?

A

lower risk of heart attack, diabetes, Alzheimer’s disease, stroke and increased longevity

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31
Q

what happens to the haptoglobin-Hb complex

A

removed by the mononuclear phagocyte system, mostly in the spleen

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32
Q

what causes facial flushing in some people when they drink alcohol

A

variant of acetaldehyde dehydrogenase enzyme –> increased circulating acetaldehyde —> general vasodilation

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33
Q

what considerably adds to the effects of Kwashiorkor

A
  • aflatoxin (from food) –> finds guanine in DNA in the liver –> cant make serum albumin problem –> oedema
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34
Q

what will the levels of haptoglobin and hemopexin be when there is intravascular haemolytic anaemia

A

low haptoglobin low hemopexin

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36
Q

main source of aflotoxin

A

peanuts

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37
Q

how many p450 genes have been identified in all organisms, and how many families have been created from that

A

8000 50 families

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39
Q

what is the absorbance of p450

A

~450nm when added with CO(absorbs blue light) –> red

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40
Q

how does lecithin help to form micelles

A

removes the surface tension of the fat

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40
Q

what happens to TG when they are remade in the enterocyte cells

A

go to liver –> add Apolipoproteins –> chylomicrons/VLDLs

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42
Q

what is the reason for poor metabolism of codeine

A

CYP2D6 inactive in 5-10% of caucasians and 2% of Asians and Arabs (codeine needs to be converted to morphine by CYP2D6 to have analgesic effect)

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42
Q

how does erythropoietin stimulate erythropoiesis

A

binds to EpoR which forms a homodimer and undergoes phosphorylation by interacting with JAK2 –> induces gene expression and protein synthesis

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42
Q

what are the functions of the different zones of the spleen

A
  • white pulp - contains lymphocytes and accessory cells which respond to antigens in the blood
  • red pulp - system of blood vessels arranged to facilitate removal of old or damaged RBCs from the circulation by macrophages
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42
Q

how much of the liver must be damaged for there to be clinical signs of liver disease

A

60% - only 40% needed

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43
Q

what is the structure of bilirubin

A

open chain of four pyrrole rings (tetrapyrrole)

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44
Q

how does alcohol affect drug metabolism

A
  • prevents drug clearance when alcohol present (competition for the cytochrome pathway)
  • promotes drug clearance by elevated CYP2E1 when alcohol is not present (induced increase in this cytochrome)
45
Q

major reaction of p450

A

hydroxylation

46
Q

what is the most human enzyme deficiency causing jaundice

A

glucose-6-phosphate dehydrogenase deficiency

48
Q

how does alcohol affect the brain

A

interacts with the lipid bilayer of the neurons - makes them leaky –> cant fire AP as well –> suppresses nervous system

49
Q

what is the cause of Crigler-Najjar syndrome

A

autosomal recessive disorder when you have total or partial lack of UGT1A1 - stops conjugation of bilirubin and therefore there is high plasma levels of unconjugated bilirubin

50
Q

what type of chemicals does the p450 system detoxify

A

all foreign chemicals with a MW less than 5000

50
Q

how is haem carried in the blood

A

initially carried on albumin and then on hemopexin –> liver

50
Q

clinical signs of alcoholism (14)

A
  • neurological disturbances
  • jaundice
  • altered breath
  • oesophageal varices
  • feminization
  • extensively scarred liver
  • portal HT
  • enlarged collateral vessels
  • ascites
  • hand tremor
  • hypogonadism
  • easy bruising
  • muscle wasting
  • infertility
51
Q

how many drinks do you have to use before alcohol dehydrogenase is working at its max rate

A

2 drinks

52
Q

what is the outcome of Crigler-Najjar syndrome is the patient is untreated

A

kernicterus = bilirubin in the brain

53
Q

T/F? p450 is not inducible

A

false p450 can be induced to upregulate

54
Q

why does the pancreas secrete zymogens instead of active enzymes

A

to stop self-digestion

55
Q

what is Crigler-Najjar syndrome

A

unable to conjugate bile at all

56
Q

what happens to conjugated bilirubin in the small intestine (2 pathways)

A
  1. bacterial proteases converts it to urobilinogen 2. converted to stercobilin –> faeces (brown colour)
57
Q

which sugars does the liver conjugate bile with

A

taurine or glycine

58
Q

what is the function of ferritin

A
  • stored in bone marrow or liver - used for erythropoiesis in bone
58
Q

two main causes of pancreatitis

A

alcohol abuse gallstones

59
Q

what are the 3 pathways that alcohol induces free radical damage of the liver

A
  • interferes with glutathione transport -> leading to depletion in mitochondria to prevent free radical damage
  • MEOS pathway (CYP2E1) loads cells with free radicals
  • alcohol promotes iron absorption - catalyst for free radical production
60
Q

what are the signs of severe dependence on alcohol

A

tremors, anxiety, sweating and vomiting

61
Q

how much bile does the human body produce per day

A

1 litre

62
Q

what is the fate of urobilinogen made by microbiota

A
  • 90% excreted into the faeces
  • 10% reabsorbed via the portal vein: –> 1% excreted through the kidneys –> urobilin when oxidised in kidneys (yellow) –> 9% recycled back into conjugated bilirubin
63
Q

which liver enzymes are increased in alcholics

A

GGT ALT CDT

64
Q

what type of enzyme is p450

A

monoxygenase

65
Q

how is bilirubin carried in the blood

A

binds serum albumin as it is highly hydrophobic

66
Q

two fold inactivation of trypsinogen

A

peptide segment occupying active site trypsin inhibitor

67
Q

pancreatic enzymes are synthesized as ……

A

zymogens

68
Q

which cytochrome is upregulated with heavy drinking

A

CYP 2E1

69
Q

what happens to haemoglobin when it gets to the liver

A

Hb is split into Haem and globin

70
Q

what happens to haem in the spleen

A
  1. broken down into Fe and biliverdin by haem oxygenase
  2. biliverdin converted by bilivirdin reductase into bilirubin , while Fe binds apoferritin to become ferritin
71
Q

what does galactosaemia do

A

causes hepatitic inflammation –> blocking bile canniliculi –> jaundice (elevated AST and normal ALP)

73
Q

what stimulates the production of erythrocytes

A

erythropoietin

74
Q

where are cytochrome p450 enzymes located

A

in the smooth ER and mitochondria (not in microsomes)

74
Q

what protein level is high in the blood with haemolytic jaundice

A

high unconjugated bilirubin

75
Q

what are the most common bile acid

A

cholic acid deoxycholic acid chenodeoxycholic acid

76
Q

what is the cause of Dubin-Johnson syndrome

A

autosomal recessive disorder due to a defect in cMCOT - increases the amount of conjugated bilirubin that is in the blood

78
Q

what happens to acetaldehyde once made by alcohol dehydrogenase from alcohol

A

converted to acetate by aldehyde dehydrogenase

80
Q

how many p450 genes are identified in humans

A

57

81
Q

where are the locations of p450 in vitro and in vivo

A
  • in vitro - microsomes - in vivo - SER
82
Q

4 actions of CCK

A
  • release of digestive enzymes from pancreas
  • release of insulin from pancreas
  • gall bladder contraction –> bile
  • goes to brain –> satiety
84
Q

function of p450 in mitochondria

A

for oxidising steroids - mostly in the adrenals

85
Q

how does bilirubin get out of the blood and into the bile

A

through cMOAT actively pumping bilirubin diglucoronide into the bile caniculi (ATP dependent)

87
Q

what is the relevance of upregulating the cytochrome CYP2E1 in alcoholism

A

it consumes NADPH so less energy is produced

88
Q

what is naltrexone

A

drug that is an opoid receptor antagonist - blocks release of dopamine that would be released with alcohol ingestion

89
Q

what is the classification system for p450 enzymes

A

CYP = abbreviation of cytochrome P450 number = family letter = subfamily number = form eg. CYP2A6

90
Q

why are women more affected by alcohol generally?

A

because females have more adipose tissue and the alcohol doesnt absorb into these cells and so more in the circulation

91
Q

function of ligandin in bile formation

A

carrier of bilirubin in cytoplasm of hepatocyte before it is conjugated (allows it to be soluble in the cell)

93
Q

what is Disulfiram (antabuse)

A

irreversible inhibitor of aldehyde dehydrogenase –> leads to unpleasant sensations when drinking alcohol

95
Q

where is acetaldehyde dehydrogenase found

A

in the mitochondria of the hepatocytes

97
Q

ancesterol p450 gene roles

A

one for steroids and one for FAs

99
Q

what allows Fe3+ to reduce into Fe2+

A

substrate binds to Fe3+ and then NADPH provides electron

100
Q

main enzyme involved in detoxification

A

p450 cytochrome

101
Q

what causes Wernicke Korsakoff Syndrome

A

depletion in thiamine

102
Q

why do premature infants tend to show jaundice more than term infants

A
  • newborn liver takes time to achieve adequate levels of Ligandin and UDP-glucuronyl transferase –> so levels of bilirubin can get higher
104
Q

where abouts and it what proportion is alcohol absorbed

A

30% in stomach 70% in gut

105
Q

why does the efficicacy of treatment of Crigler-Najjar syndrome with phototherapy decrease as the patient ages

A

due to increased thickness of skin and body surface/weight ratio

106
Q

what is the major pathway of alcohol metabolism? And what are the minor pathways

A

major = alcohol dehydrogenase minor = MEOS and catalase

107
Q

what are the main causes of haemolysis

A
  • external attack on red cells by pathogens (bacteria and parasites) - congenital or genetic factors
108
Q

what causes the pot belly in children with Kwashiorkor disease

A

enlarged fatty liver low serum albumin oedema leads to fluid accumulation in the belly

110
Q

what are the 3 mechanisms in which p450 can be upregulated

A
  • activate the gene (dioxin and phenobarbital) -stabilise mRNA - protect p450 from turnover
111
Q

what is the cell that removes the RBCs from the circulation

A

macrophages

112
Q

what happens to globin in the liver

A

hydrolysed into amino acids

113
Q

what value of bilirubin is needed for jaundice to occur

A

>35 micromolar (3x normal value)

114
Q

what attaches p450 to the SER/mitochondrial membrane

A

a hydrophobic protein foot

114
Q

when in benzpyrene produced

A

from combustion products - undergoes 2 different mechanisms –> one leads to carcinogen

115
Q

how does G6PD cause jaundice

A

reduced production of glutathione –> RBC age reduces –> haemolytic anaemia

116
Q

how do zymogens stay inactive

A

have a peptide segment which is part of the enzyme protein itself, occupying the active site

117
Q

how does the drug Orlistat work

A

inhibits lipase that breaks down the TG –> fatty stools

118
Q

what are Heinz bodies

A

precipitated Hb in RBCs

120
Q

what happens to acetate (made from alcohol)

A

oxidised for energy (TCA cycle) or converted to fat

121
Q

how does the macrophage know that its time to remove a RBC

A

responds to altered surface molecules on the aged RBC - exposure of phosphatidyl serine - reduced content of sialic acid anchored to glycophorin - oxidative damage - more phosphatidylserine flips to the outer side of the membrane

122
Q

function of alcohol dehydrogenase

A

conversion of alcohol to acetaldehyde

122
Q

what is the advantage of having G6PD

A

confers resistance to malaria

123
Q

which enzymes will be elevated in the blood in someone with jaundice

A

ALT, AST, GGT, ALP

124
Q

what is the precursor of RBCs

A

reticulocytes

126
Q

what activates chymotrypsin

A

enteropeptidase on enterocytes

127
Q

how is blood alcohol measured

A

gas chromatography

129
Q

is haemolytic jaundice pre/post hepatic

A

pre-hepatic

130
Q

function of hemopexin

A

recycles iron

131
Q

how many electrons can p450 deal with at a time

A

1 - it is a monoxygenase (therefore need 2 p450 to undergo reduction and oxidation when hydroxylating a substrate)

132
Q

2 major causes of neonatal jaundice

A
  • increased haem catabolism (due to change from HbF to HbA) - immaturity of the liver in bilirubin conjugation and excretion