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Flashcards in Clinical Biochemistry Deck (44):
1

Lead Poisoning

Typically children who ingest paint, adults (factory worker, bullets)

Decreased heme synthesis and increased RBC protoporyphryin

Affected Enzyme: Ferrochelatase and ALA dehydratase

Accumulated Substrate: Protoporphyrin, D-ALA in blood

Symptoms: microcytic (sideroblastic) anemia, GI (colicky abdominal pain, lead lines on gums/metaphyses) and Kidney disease
Adults: headache, memory loss, demylination (wrist/foot drops)
Children: mental deterioration
Increase in pyridoxal phosphate during poisoning

Labs: basophilic stippling (inhibition of rRNA degradation)
increased iron, normal/decreased TIBC, increased ferritin

Treatment: dimercaprol and EDTA
Succimer for children

2

Acute intermittent porphyria

AD

Affected enzyme: porphobilogen deaminase (uroporphobionogen III synthase)

Accumulated substrate: Porphobilogen, D-ALA
(coporphobilinogen in urine)

Symptoms: painful abdomen, port wine colored urine (darkens on exposure to light), polyneuropathy, psychological disturbances (anxiety)

Precipitated by drugs that induce CYP450 (phenytoin, griseofulvin, phenoarbital)-due to CYP450 needing heme, increase in ALA synthase cannot be matched by deficient enzyme), alcohol and starvation

Treatment: glucose, heme which inhibit ALA synthase

3

Porphyria cutanea tarda

Most common
Affected enzyme: Uroporphyrinogen decarboxylase

Accumulated substrate: Uroporphyrin (tea color urine)

Symptoms: blistering when exposed to sun exposure (due to porphyrin mediated superoxide free radical formation)
Edema, pruiritis, pain and erythema

4

Pyruvate carboxylase

Irreversible enzyme of gluconeogenesis

Pyruvate to oxaloacetate

Happens in mitochondria

Requires biotin, ATP, activated by acetyl CoA

5

Phosphoenolpyruvate

Irreversible enzyme of gluconeogenesis

In cytosol

Oxaloacetate to phospenopyruvate

Requires GTP

6

Fructose 1,6 bisphosphatase

Irrevesrible enzyme of gluconeogenesis

In cytosol

Fructose 1,6 BP to fructose 6-P

7

Glucose 6 phosphatase

Irreversible enzyme of gluconeogenesis

Happens in ER

Glucose 6-P to glucose

8

Isocitrate dehydrogenase

Irreversible part of TCA
Isocitrate to a keto glutarate

Produces NADH and CO2

Inhibited by ATP and NADh
Activated by ADP

9

a ketocgulatarate

Irreversible part of TCA
Produces NADH and CO2

Inhibited by Succinyl CoA, NADH and ATP

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Succinyl CoA to Succinate

Produces GTP and CoA in TCA

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Succinate to Fumarate

Produces FADH2

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Malate to NADH

Pruduces NADH

13

TCA yields

3 NADH
1 FADH2
2CO2
1 GTP per acetyl CoA
Add up to 10 ATP per acetyl CoA x2 for glucose

14

Glucokinase/hexokinase

Uses ATP
Glucose to glucose 6 phosphate

Hexokinase Inhibited by glucose 6 P
Glucokinase inhibited by fructose 6P (liver and B cells)

Both inhibited by ATP, Citrate
Accelerated by AMP and Fructsoe 2,6 BP

15

ATP producing steps of glycolysis

1,3 Bisphosphgylcerate to 3 Phosphoglycerate using phosphoglycerate kinase


Phosphoenolpyrugate to pyruvate using pyruvate kinase
Inhibited byt ATP, alanine, cAMP
Activated by fructose 1,6 bisphosphate

16

Fructose 2, 6 bisphosphate and fasting/fed state

Fasting state: increaesd glucagon, increased cAMP Increased PKA Increased FBPase-2 increasing fructoese 6 phosphate leading to glucogneeogenesis

Fed state: increased insulin, decreased cAMP, decreased PKA, decrease FBPase 2, increased PFK leading into more glycolysis

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Pyruvate dehydrogenase activation

increased NAD/NADH ration

increased ADP

Increased Ca2+

18

Happens in the mitochondria

Fatty acid oxidation
Acetyl CoA production
TCA cycle
Oxidative phosphorylation

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Happens in Cytoplasm

Glycolysis
Fatty acid synthesis
HMP shunt
Protein synthesis (RER)
Steroid synthesis (SER)
Cholesterol synthesis

20

Kwashiorkor

Protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty change due to decreased apolipoprotein synthesis), anemia

Small child with swollen belly

21

Marasmus

Total calorie malnutrition resulting in tissue and muscle wasting , loss of subcutaneous fat, and variable edema

22

Robertsonian Translocation

Nonreciprocal chromosomal translocation that involves chromsomes 13, 14, 14, 21 and 22

Long arms of acrocentric (centromeres near the ends) fuse at the centromere and the 2 short arms are lost

Balanced translocations normally do not cause any abnormal phenotype

Unbalanced causes miscarriage, stillbirth, and chromosomal imbalance

23

Williams Syndrome

Congenital microdeletion of long arm of chromosome 7 (deleted region includes elastin gene)

Findings: elfin facies, intellectual disability, hypercalcemia well developed verbal skills, extreme friendliness, cardiovascular problems

24

22q11 deletion syndromes

Variable presentation
Cleft palate,, abnromal facies, thymic aplasia (T Cell deficiency), cardiac defects, hypocalcemia,

Aberrant development of 3rd and 4th brachial pouches

25

Down Syndrome

trisomy 21

Findings: intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, gap between 1st 2 toes, duodenal atresia, Hisrchsprung disease, congenital heart disease (ostium primum type ASD), brushfield spots (white spots on iris)

Increased risk of ALL, AML, and Alzheimer disease

Most due to meitotic nondisjunction of homologous chromosmes-omen over 45 years old
4% due to Robertsonian translocation
1% due to mosacism

First trimester ultrasound: increased nuchal tranlucency, and hypoplastic nasal bone, serum PAPP-A decreased, B-hCG is increased

Second trimester:
decreased a-fetoprotein, increased B-hCG, decreased estriol, increased inhibin A

26

Edwards syndrome

trisomy 18

Findings: severe intellectual disability, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent ocipput, congenital heart disease, microphtalmia, cataracts,
NTDs, arnold chiari, PDA, Meckel diverticulum

First trimester: PAPP-A and B-hCG are decreased in first trimester
Second trimster: decreased aFP, decreased B-hCG, decreased estriol, decreased or normal inhibin A

Death within 1 year

27

Patau syndrome

Trisomy 13

Findings: sever intellectual disbability, rocker bottom feet, microphtalmia, microcephaly, clef lip/cleft Palate, holoprsencephay, microcephal, absent ofactor bulb, NTDs, polydactyly, congenital heart disease, omphalocele, PCKD, cyclops

Death within 1 year

First trimester: decreased B hCG and Decreased PAPP-A
increased nuchal translucency

28

Autosomal Recessive diseases

Albinism, ARPKD, cystic fibrosis, glycogen storage diseases, hemochromatosis, Kartagener syndrome, mucopolysaccharidoses (not Hunter), phenylketonuria, sickle cell, Sphingolipdoses (except Fabry), thalassemias, Wilson disease

29

X linked recessive disorders

Bruton agammaglobulinemia, Wiskott Aldrich, Fabry, G6PD deficiency, oclar albinism, Lesch Nyhan syndrome, Duchenne and Beckers, Hunter, Hemophilia A and B, ornithine transcarbamylase deficiency

30

Autosomal Dominant Diseases

ADPKD, Familial adenomatous polyposis, familial hypercholesterolemia, hereditary hemorrhagic telangiectasia, herditary spherocytosis, Huntingtons, Marfan, MEN syndromes, NF1, NF2, Tuberous sclerosis, VHL

31

Type I Collagen

Bone, Tendons, Late wound repair, dentin, fascia, cornea

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Type II Collagen

Cartialge, vitreous body, nucleus pulposus

33

Type III Collagen

Arteries, reticulin in skin, uterus, fetal tissue, granulatio tissue, organs, lymphocytes

34

Type IV collagen

Basement membrane
Basal lamina
Lens

35

Transformation

Ability to take up naked DNA (from cell lysis) from environment

S. pneumo, H. influenza, and Neisseria

Adding deoxyribonuclease to environment will degrade naked DNA in medium leading to no transformation seen

36

Conjugation (F+ x F-) and (Hfr x F-)

F+xF- = F+ plasmid contains genes required for sex pilus and conjugation.
Bacteria without this plasmid are termed F-
Plasmid (dsDNA) is replicated and transferred through pilus from F+ cell
No transfer of chromosomal genes

Hfr x F-= F+ plasmid can become incorporated into bacteria chromsomal DNA termed high frequency recombination cell
Replication of incorporated plasmid DNA may include some flanking chromosomal DNA
transfer of plasmid and chromsomal genes

37

Transposition

Segment of DNA (transposon) that can jump (excision and reintegration) from one location to another
Can transfer genes from plasmid to chromosome and vice versa

When excision occurs may include some flankin chromsomal DNA which can be incorporated into a plasmid and transferred to another bacterium

Antibiotic resistance genes on R plasmid

38

Generalized transduction

Packaging event

Lytic phage infects bacterium leading to cleavage of bacterial DNA

Parts of bacterial chromosomal DNA may become packaged in viral capsid

Phage infects another bacterium transfering these genes

39

Specialized transduction

An excision event

Lysogenic phage infects bacterium
viral DNA incorporates into bacterial chromosome

When phage DNA is excised, flanking bacterial genes may be excised with it

Phage is packaged into phage viral capsid and can infect another bacterium

Shiga-like toxin
Botulinum toxin
Cholera toxin
Diptheria toxin
Erythrogenic toxin of Strep. pyogenes

40

Recombination

Exchange of genes between two chromosomes by crossing over within regions of significant base sequence homology

Passed onto generations-traits present in progeny that weren't in parents

41

Reassortment

When viruses with segmented genomes exchange segments

High frequency recombination

Causes worldwide influenza pandemics

passed onto generations

42

Complementation

When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional protein

The nonmutated virus complements the mutated one by making a functional protein that serves both viruses

43

Phenotypic mixing

Occurs with simultaneous infection of a cell with 2 viruses
Genome of virus A can e partially or completely coated with the surface proteins of virus B

Type B protein coat determines the tropism (infectivity) of the hybrid virus

The progeny do not have the type B protein coat but rather have the orginal type A coat

44

Interference

Inhibition of one virus replications and/or release by second virus infecting the same cell