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Flashcards in biochemistry Deck (132)
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1

what is classified as binge drinking

drinking more than 10 standard drinks in one sitting

2

how does alcohol lead to dehydration

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

3

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

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

4

what is haemosiderin

polymer of ferritin

5

what is function of the Standard Ames Assay

to check whether chemicals are mutagenic or not

6

treatment of Crigler-Najjar syndrome

- phototherapy (10-12 hours per day)

- liver transplant

6

what are the types of alcohol induced liver damage

- fatty liver

- alcoholic hepatitis

- alcoholic cirrhosis

6

how much of the bile salts are reabsorbed

95%

7

what is the function of haptoglobin

- binds to the Hb that is released from RBCs when they are haemolysed at sites remote from the spleen

8

what holds the Fe2+ in p450

a cysteine anchor forms a ligand to the Fe in Haem

9

what is a microsome

artefact of breaking SER

10

what is the mainstay detoxification method of p450

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

10

where is the active site on p450

right next to the Haem group

11

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

cerebral cortex - impaired judgement and info processing

forebrain - memory and emotions

cerebellum - balance and movement

brainstem - breathing and circulation

12

function of Fe in p450

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

12

what are the two pathways for benzopyrene

- undergoes phase one and two reactions to become a kidney safe product

- undergoes different phase 1 reaction which then goes through p450 --> carcinogen

12

dioxin is p450 dependent or independent to become mutagenic

independent - mutagenic without p450

12

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

- 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)

13

what causes Gilberts disease

decreased conjugation of bilirubin and decreased uptake in some cases

14

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

CYP2D6

15

what two levels in the serum will show pancreatitis

serum amylase and/or serum lipase elevated

17

what is the correlation between p450 and steroid synthesis

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

18

how do you get dioxin in the environment

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

19

what causes gall stones

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

20

which p450 enzyme is induced with dioxin

CYP1A1

20

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

6+ males 4+ women

21

how can alcohol lead to hypoglycaemia

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

22

action of phenobarbitol

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

23

what does conjugation of bilirubin mean

adds sugars to it to make it more soluble

23

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

CCK and secretin

24

where is bilirubin produced

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

24

what are bile salts made of

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

25

what happens to the alcohol metabolism with sustained alcohol intake

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

25

how much alcohol is cleared per hour

0.015%

26

what equation does p450 typically catalyse

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

27

how does phototherapy treat Crigler-Najjar syndrom

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

29

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

- benzopyrene

- aflatoxin

30

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

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

31

what happens to the haptoglobin-Hb complex

removed by the mononuclear phagocyte system, mostly in the spleen

32

what causes facial flushing in some people when they drink alcohol

variant of acetaldehyde dehydrogenase enzyme --> increased circulating acetaldehyde ---> general vasodilation

33

what considerably adds to the effects of Kwashiorkor

- aflatoxin (from food) --> finds guanine in DNA in the liver --> cant make serum albumin problem --> oedema

34

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

low haptoglobin low hemopexin

36

main source of aflotoxin

peanuts

37

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

8000 50 families

39

what is the absorbance of p450

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

40

how does lecithin help to form micelles

removes the surface tension of the fat

40

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

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

42

what is the reason for poor metabolism of codeine

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)

42

how does erythropoietin stimulate erythropoiesis

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

42

what are the functions of the different zones of the spleen

- 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

42

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

60% - only 40% needed

43

what is the structure of bilirubin

open chain of four pyrrole rings (tetrapyrrole)

44

how does alcohol affect drug metabolism

- 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

major reaction of p450

hydroxylation

46

what is the most human enzyme deficiency causing jaundice

glucose-6-phosphate dehydrogenase deficiency

48

how does alcohol affect the brain

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

49

what is the cause of Crigler-Najjar syndrome

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

what type of chemicals does the p450 system detoxify

all foreign chemicals with a MW less than 5000

50

how is haem carried in the blood

initially carried on albumin and then on hemopexin --> liver

50

clinical signs of alcoholism (14)

- 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

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

2 drinks

52

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

kernicterus = bilirubin in the brain

53

T/F? p450 is not inducible

false p450 can be induced to upregulate

54

why does the pancreas secrete zymogens instead of active enzymes

to stop self-digestion

55

what is Crigler-Najjar syndrome

unable to conjugate bile at all

56

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

1. bacterial proteases converts it to urobilinogen 2. converted to stercobilin --> faeces (brown colour)

57

which sugars does the liver conjugate bile with

taurine or glycine

58

what is the function of ferritin

- stored in bone marrow or liver - used for erythropoiesis in bone

58

two main causes of pancreatitis

alcohol abuse gallstones

59

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

- 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

what are the signs of severe dependence on alcohol

tremors, anxiety, sweating and vomiting

61

how much bile does the human body produce per day

1 litre

62

what is the fate of urobilinogen made by microbiota

- 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

which liver enzymes are increased in alcholics

GGT ALT CDT

64

what type of enzyme is p450

monoxygenase

65

how is bilirubin carried in the blood

binds serum albumin as it is highly hydrophobic

66

two fold inactivation of trypsinogen

peptide segment occupying active site trypsin inhibitor

67

pancreatic enzymes are synthesized as ......

zymogens

68

which cytochrome is upregulated with heavy drinking

CYP 2E1

69

what happens to haemoglobin when it gets to the liver

Hb is split into Haem and globin

70

what happens to haem in the spleen

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

what does galactosaemia do

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

73

what stimulates the production of erythrocytes

erythropoietin

74

where are cytochrome p450 enzymes located

in the smooth ER and mitochondria (not in microsomes)

74

what protein level is high in the blood with haemolytic jaundice

high unconjugated bilirubin

75

what are the most common bile acid

cholic acid deoxycholic acid chenodeoxycholic acid

76

what is the cause of Dubin-Johnson syndrome

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

78

what happens to acetaldehyde once made by alcohol dehydrogenase from alcohol

converted to acetate by aldehyde dehydrogenase

80

how many p450 genes are identified in humans

57

81

where are the locations of p450 in vitro and in vivo

- in vitro - microsomes - in vivo - SER

82

4 actions of CCK

- release of digestive enzymes from pancreas

- release of insulin from pancreas

- gall bladder contraction --> bile

- goes to brain --> satiety

84

function of p450 in mitochondria

for oxidising steroids - mostly in the adrenals

85

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

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

87

what is the relevance of upregulating the cytochrome CYP2E1 in alcoholism

it consumes NADPH so less energy is produced

88

what is naltrexone

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

89

what is the classification system for p450 enzymes

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

90

why are women more affected by alcohol generally?

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

91

function of ligandin in bile formation

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

93

what is Disulfiram (antabuse)

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

95

where is acetaldehyde dehydrogenase found

in the mitochondria of the hepatocytes

97

ancesterol p450 gene roles

one for steroids and one for FAs

99

what allows Fe3+ to reduce into Fe2+

substrate binds to Fe3+ and then NADPH provides electron

100

main enzyme involved in detoxification

p450 cytochrome

101

what causes Wernicke Korsakoff Syndrome

depletion in thiamine

102

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

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

104

where abouts and it what proportion is alcohol absorbed

30% in stomach 70% in gut

105

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

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

106

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

major = alcohol dehydrogenase minor = MEOS and catalase

107

what are the main causes of haemolysis

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

108

what causes the pot belly in children with Kwashiorkor disease

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

110

what are the 3 mechanisms in which p450 can be upregulated

- activate the gene (dioxin and phenobarbital) -stabilise mRNA - protect p450 from turnover

111

what is the cell that removes the RBCs from the circulation

macrophages

112

what happens to globin in the liver

hydrolysed into amino acids

113

what value of bilirubin is needed for jaundice to occur

>35 micromolar (3x normal value)

114

what attaches p450 to the SER/mitochondrial membrane

a hydrophobic protein foot

114

when in benzpyrene produced

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

115

how does G6PD cause jaundice

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

116

how do zymogens stay inactive

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

117

how does the drug Orlistat work

inhibits lipase that breaks down the TG --> fatty stools

118

what are Heinz bodies

precipitated Hb in RBCs

120

what happens to acetate (made from alcohol)

oxidised for energy (TCA cycle) or converted to fat

121

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

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

function of alcohol dehydrogenase

conversion of alcohol to acetaldehyde

122

what is the advantage of having G6PD

confers resistance to malaria

123

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

ALT, AST, GGT, ALP

124

what is the precursor of RBCs

reticulocytes

126

what activates chymotrypsin

enteropeptidase on enterocytes

127

how is blood alcohol measured

gas chromatography

129

is haemolytic jaundice pre/post hepatic

pre-hepatic

130

function of hemopexin

recycles iron

131

how many electrons can p450 deal with at a time

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

132

2 major causes of neonatal jaundice

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