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USMLE Step 1 > Biochemistry > Flashcards

Biochemistry Flashcards

1
Q

Drugs that inhibit dihydrofolate reductase

A

Methotrexate
Trimethoprim
Pyrimethamine

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2
Q

Which drug inhibit thymidine synthase

A

5-fluorouracil (5-FU)

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3
Q

Drug that inhibit dihydroorotate dehydrogenase

A

Leflunomide

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4
Q

Which drug inhibits ribonucleotide reductase

A

Hydroxyurea

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5
Q

Which drug inhibits de novo purine synthesis

A

6-mercaptopurine (6-MP) and azathioprine (prodrug)

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6
Q

Which drugs inhibit inosine monophosphate dehydrogenase

A

Mycophenolate and ribavirin

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7
Q

Pathology of adenosine deaminase deficiency

A

ADA degrades adenosine and deoxyadenosine
Deficiency —> increased dATP —> toxicity to lymphocytes
Major cause of AR SCID (severe combined immunodeficiency)

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8
Q

Pathology of Lesch-Nyhan syndrome

A

Deficiency of HGPRT - hypoxanthine guanine phosphoribosyl transferase —> excess purine production and uric acid
X-linked recessive

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9
Q

Signs and symptoms of Lesch-Nyhan syndrome

A

HGPRT

  • Hyperuricemia
  • Gout
  • Pissed off (aggression, self-mutilation)
  • Retardation
  • DysTonia
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10
Q

Treatment of Lesch-Nyhan syndrome

A

Allopurinol

Febuxostat (2nd line)

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11
Q

Drugs that inhibit xanthine oxidase

A

Allopurinol

Febuxostat

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12
Q

Drug that increase uric acid excretion

A

Probenecid

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13
Q

Features of the genetic code

A
  1. Unambiguous
  2. Redundant/degenerate (except for methionine - AUG - and tryptophan - UGG)
  3. Commaless/non-overlapping
  4. Universal
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14
Q

Function of DNA topoisomerases

A

Create single/double-stranded break in helix to add or remove supercoils

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15
Q

Drugs that inhibit topoisomerases

A 
Eukaryotic:
Topoisomerase 1 - Irinotecan/topotecan 
Topoisomerase 2 - Etoposide/Teniposide
Prokaryotic:
Topoisomerase 2 (DNA gyrase) and IV - fluoroquinolone
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16
Q

Function of the DNA polymerases

A

DNA polymerase III - adds DNA bases to leading and lagging strands
DNA polymerase I - Degrades RNA primer and replaces it with DNA
Both are prokaryotic

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17
Q

Types of mutations in DNA and eg of diseases

A

Silent - codes same DNA
Missense - nucleotide substitution (sickle cell disease)
Nonsense - codes stop codon
Frameshift - deletion/insertion of nucleotide not divisible by 3 (Duchenne muscular dystrophy, Tay-Sachs Disease)
Splice site - eg retained intron

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18
Q

3 types of single-stranded DNA repair (and associated diseases)

A

1- nucleotide excision repair:
endonuclease release oligonucleotides with damaged bases. DNA polymerase and ligase fill and seal gap. G1 cycle. Xeroderma pigmentosa
2- Base excision repair:
GEL PLease - glycosylase, endonuclease, lyase, polymerase B, ligase
Throughout cell cycle. Spontaneous/toxic deamination
3- Mismatch repair:
Newly synthesized strands. G2 phase. Lynch syndrome (HNPCC)

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19
Q

Double-stranded DNA repair and associated pathologies

A

Non-homologous end joining

Ataxia telangiectasia, breast/ovarian CA (BRCA1), Fanconi anaemia

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20
Q

Start and stop codons (mRNA)

A 
Start: AUG or rarely GUG (AUG inAUGurates protein synth)
Stop:
UGA (U Go Away)
UAA (U Are Away)
UAG (U Are Gone)
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21
Q

Types of eukaryotic RNAs

  • which polymerase makes what
  • what substance inhibits it
A 
rRNA 
- RNA polymerase I
mRNA
- RNA polymerase II
- alpha-amanitin (from death cap mushrooms), cx severe hepatotoxicity
tRNA
- RNA polymerase III
- Actinomycin D (pro and eukaryotes)
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22
Q

Drug that inhibit prokaryotic RNA

A

Rifampicin

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23
Q

Antibodies (and diseases) associated with snRNPs

A

snRNP = small nuclear ribonucleoprotein

  • Anti-Smith to spliceosomal snRNP: SLE
  • Anti-U1 RNP: MCTD (mixed connective tissue disease)
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24
Q

3 types of cells (based on cell cycle) with eg

A

Permanent - neurons, skeletal and cardiac muscles, RBCs
Stable (quiescent) - hepatocytes and lymphocytes
Labile - bone marrow, hair follicles, gut epithelium, skin, germ cells

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25
Q

I-cell disease: pathophysiology

A

Inclusion cell disease/mucolipidosis type II
Inherited lysosomal storage ds - defect in N-acetylglucosaminyl-1-phosphotransferase —> failure of golgi to phosphorylate mannose residues on glycoproteins —> proteins secreted rather than delivered to lysosomes

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26
Q

I-cell disease: signs and symptoms

A

Coarse facial features
Clouded corneas
Restricted joint movements
High plasma level of lysosomal enzymes

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27
Q

Vesicular trafficking proteins

A

COPI - retrograde, golgi-golgi, cis-golgi to ER
COPII - anterograde, ER to cis-Golgi
Clathrin: trans-golgi to lysosomes, plasma membrane to endosomes

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28
Q

Function of peroxisomes

A

Catabolism of fatty acids (B-oxidation), amino acids, ethanol

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29
Q

Pathophysiology of peroxisomal disorders

A

Deficit in synthesis of plasmalogens (NB phospholipid in myelin)
Cx neurological diseases: Zellweger syndrome and Refsum disease

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30
Q

Features of peroxisomal diseases

A

Zellweger syndrome:
- hypotonia, seizures, hepatomegaly, early death
Refsum disease:
- scaly skin, cataracts/night blindness, ataxia, shortening of 4th toe, epiphyseal dysplasia

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31
Q

Types of intermediate filaments

A 
Vimentin
Desmin 
Cytokeratin
GFAP
Neurofilament
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32
Q

What does vimentin stain and identify?

A

Mesenchymal tissue

  • Mesenchymal tumours (eg sarcomas)
  • Endometrial CA
  • RCC
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33
Q

What does desmin stain and identifies?

A

Muscles - muscle tumours eg rhabdomyosarcoma

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34
Q

What does cytokeratin stain and identifies?

A

Epithelial cells

Epithelial tumours eg squamous cell CA

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35
Q

What does GFAP stain and identifies?

A

Glial fibrillary acid proteins - neuroglia (eg astrocytes, Schwann cells, oligodendrocytes)
Astrocytoma, glioblastoma

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36
Q

Describe Kartagener syndrome

A 
Primary ciliary dyskinesia - due to defect of dynein arm
Cx:
-male and female infertility
-increased risk of ectopics
-bronchiectasis
-recurrent sinusitis and chronic ear infections
-conductive hearing loss
-situs inversus
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37
Q

MOA of cardiac glycosides

A

Eg digoxin and digitoxin (also ouabain - arrow poison)
Inhibits Na/K ATPase - indirect inhibition of Na/Ca exchanger —> increased intracell [Ca] —> increased cardiac contractility

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38
Q

Types of collagens (and assoc diseases)

A

Be (So Totally) Cool, Read Books
Type I - Bone, Skin, Tendons, late wound repair.. Osteogenesis Imperfecta Type 1
Type II - Cartilage
Type III - Reticular.. vascular type of Ehlers-Danlos (ThreE D)
Type IV - Basement membrane.. Alport and Goodpasture syndrome

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39
Q

Steps of collagen synthesis

A

1- synthesis: translation of preprocollagen (Gly-X-Y)
2- hydroxylation: of specific proline and lysine residues, requires Vit C
3- glycosylation: forms procollagen triple helix by hydrogen and disulfide bonds
4- exocytosis
5- Proteolytic processing: cleaves disulfide rich terminal regions —> tropocollagen
6- Cross-linking: covalent lysine-hydroxylysine cross-linking by lysyl oxidase

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40
Q

Which step of collagen synthesis does scurvy affect?

A

2- hydroxylation

Due to Vit C deficiency

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41
Q

Which step of collagen synthesis does osteogenesis imperfecta affect?

A

3- glycosylation

Can’t form triple helix

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42
Q

Which step of collagen synthesis does Ehlers-Danlos affect

A

5- Proteolytic processing

6- Cross-linking

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43
Q

Which step of collagen synthesis does Menkes disease affect?

Describe Menkes

A

6- Cross-linking
X-linked recessive ds
Mutation in ATP7A gene —> decreased Cu absorption and transport protein —> lack of Cu for lysyl oxidase

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44
Q

Signs and symptoms of Menkes disease

A

Brittle, kinky hair
Growth retardation
Hypotonia
FTT

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45
Q

Genetics and manifestations of osteogenesis imperfecta

A 
Variety of gene defects, commonly COL1A1 and COL1A2
Most common = autosomal dominant
Patients can’t “BITE”
Bones - multiple #
I (eyes) - blue sclera
Teeth - dentinogenesis imperfecta
Ear - hearing loss (abn ossicles)
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46
Q

Features of Ehlers-Danlos syndrome

A 
Hyperextensible skin
Hyper mobile joints and dislocations
Bleeding tendencies
Berry and aortic aneurysms
Organ rupture
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47
Q

3 types of Ehlers Danlos syndrome

A

Hypermobility type - joint instability, most common type
Classical type - Type V collagen (COL5A1/2), joint and skin sx
Vascular type - Type III collagen, vascular and organ rupture

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48
Q

Genetics of Marfan’s syndrome

A

AD connective tissue ds —> affects skeleton, heart and eyes

FBN1 gene mutation on chromo 15 —> decreased fibrillin (glycoprotein that forms sheath around elastin)

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49
Q

Features of Marfan’s

A

Skeleton:
- Tall with long extremities, pectus carinatum/excavatum, hypermobile joints, long tapering fingers and toes (arachnodactyly)
Heart:
- cystic medial necrosis of aorta, aortic incompetence, dissecting aortic aneurysms, floppy mitral valve
Eyes:
- Subluxation of lenses

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50
Q

Function of FISH

A 
Fluorescent in situ hybridization
Localization of genes and direct visualization of chromosomal anomalies
- Microdeletion
- Translocation
- Duplication
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51
Q

Define mosaicism and outline the 2 types

A

Presence of 2 distinct cell lines in same individual
Somatic - mutation after fertilization
Gonadal - mutation in egg or sperm cells

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52
Q

Describe Mccune-Albright syndrome

  • genetics
  • s&s
A

Somatic mosaicism - spontaneous mutation of GNAS (G-protein signalling).
Dx need 2 of:
- unilateral cafe au lait spots with ragged edges
- polyostotic fibrous dysplasia
- endocrinopathy: precocious puberty, testicular abn, hyperthyroid, GH excess, Cushing’s

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53
Q

Locus heterogeneity and eg of disease

A

Mutation at different loci can produce similar phenotype

Eg albinism

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54
Q

Loss of heterozygosity and eg of diseases

A

mutation in a tumour suppressor gene, complementary allele must be developed before CA develops.
Eg retinoblastoma, HNPCC, Li-Fraumeni

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55
Q

Define allelic heterogeneity and eg of disease

A

Different mutations at same locus produce same phenotype

Eg B-thalassemia

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56
Q

Define heteroplasmy

A

Presence of both mutated and normal mitochondrial DNA regulating in variable expression of mt-inherited disease

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57
Q

Define uniparental disomy

A

Offspring inherits 2 pairs of chromosomes from 1 parent and none from other
Heteroisomy - meiosis I error
IsoIsomy - meiosis II error

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58
Q

Define genetic imprinting and eg 2 diseases

A

At same loci, only 1 allele is active (other is imprinted/inactivated by methylation)

  • Prader-Willi
  • Angelman syndrome
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59
Q

Describe Prader-Willi syndrome

A

Chromo 15
P = paternal. Maternal imprinting with paternal gene deleted/mutated.
Hyperphagia, obesity, ID, hypogonadism, hypotonia
25% due to maternal uniparental disomy (2 pairs of imprinted maternal genes received)

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60
Q

Describe Angelman syndrome

A

Chromo 15
AngelMan = maternal. Paternal imprinting, maternal gene deleted/mutated
Severe ID, seizures, ataxia, inappropriate laughter “happy puppet”
5% due to paternal uniparental disomy

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61
Q

Examples of X-linked dominant diseases

A

Hypophosphataemic rickets
Fragile X syndrome
Alport syndrome

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62
Q

Genetics of cystic fibrosis

A

AR

Defect in CFTR gene on Chromo 7 - deletion of Phe508

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63
Q

Pathophysiology of cystic fibrosis

A

Defect in the chloride channel that secretes Cl in lungs and GI and reabsorb Cl in sweat glands
Mutation —> misfolded protein —> retained in RER
Decreased Cl (and H2O) secretion + compensatory Na resorption
Contraction alkalosis and hypoK
Abn thick mucus

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64
Q

Diagnosis of cystic fibrosis

A

Sweat test: [Cl] in sweat > 60mEq/L

Increased immunoreactive trypsinogen (newborn screening)

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65
Q

Manifestations of cystic fibrosis

A

Resp:
- recurrent pulm infections (S aureus in infancy, Pseudomonas in adolescence), chronic bronchitis and bronchiectasis (reticulonodular on CXR), opacification of sinuses
GIT:
- pancreatic insuff, malabsorption with steatorrhoea, ADEK deficiency, biliary cirrhosis, liver ds, meconium ileus in newborns
Other: infertility in men, subfertility in women. Nasal polyps, clubbing

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66
Q

Treatment of cystic fibrosis

A

Chest physio, B-agonists, aerosolized dornase alpha (DNAse), hypertonic saline
Azithromycin (anti-inflamm)
Ibuprofen (slows ds progression)
Pancreatic enzymes

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67
Q

Examples of AD diseases

A

Achondroplasia, AD polycystic kidney disease, FAP, familial hypercholesterolemia, hereditary spherocytosis, hereditary haemorrhagic telangiectasia, Huntington disease, Li-Fraumeni, Marfan, MEN, neurofibromatosis I & II, tuberous sclerosis, von Hippel-Lindau

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68
Q

Eg of AR diseases

A

Albinism, ARPKD, cystic fibrosis, glycogen storage ds, haemochromatosis, Kartagener syndrome, mucopolysaccharidoses (except Hunter), phenyketonuria, sickle cell, sphingolipidoses (except Fabry), thalassemias, Wilson disease

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69
Q

List the X-linked recessive disorders

A

Oblivious Females Will Often Give Her Boys Her x-Linked Disorders:

  • Ornithine transcarbamylase deficiency
  • Fabry disease
  • Wiskott-Aldrich syndrome
  • Ocular albinism
  • G6PD deficiency
  • Hemophilia A & B
  • Bruton agammaglobulinemia
  • Hunter syndrome
  • Lesch-Nyhan
  • Duchenne (and Becker) dystrophy
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70
Q

Define lyonization

A

In X-linked recessive ds:

Female carriers invariably affected depending on pattern of inactivation of X-chromosome carrying mutant vs normal gene

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71
Q

Duchenne muscular dystrophy

  • genetics
  • lab findings and dx
  • features and major cx of death
A

-X-linked recessive, frameshift or nonsense
Deleted dystrophin (DMD) gene - largest protein-coding gene. Anchors crib to transmembrane alpha/beta-dystroglycan.
- increased CK and aldolase. Dx = genetic testing
- Gower sign, calf pseudohypertrophy , waddling. Weakness begins in pelvic girdle and progress superiority.
Dilated cardiomyopathy cx death

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72
Q

Becker muscular dystrophy

- genetics

A

X-linked, non-frameshift deletions in DMD —> functional gene therefore less severe than Duchenne

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73
Q

Myotonic type 1 muscular dystrophy

  • genetics
  • features
A

AD
CTG trinucleotide repeats in DMPK gene —> abn expression of myotonin protein kinase
CTG - Cataracts, Toupee, Gonadal atrophy + myotonia, arrhythmia

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74
Q

Fragile X sydrome - genetics

A 
X-linked dominant
Trinucleotide repeats (CGG) in FMR1 gene —> hypermethylation —> decreased expression
Most common cx of inherited ID and autism. 2nd most common genetic cx of ID (after Down’s)
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75
Q

Fragile X syndrome - features

A

Trinucleotide repeats CGG: Chin (protrude), Giant Gonads

  • Long face with large jaw
  • Large exerted ears
  • Mitral valve prolapse
  • Post-pubertal macro-orchidism
  • Autism
76
Q

List the trinucleotide repeat diseases

A 
“Try Hunting for My Fragile Free-range eggs”
Huntington (CAG) - Caudate has low ACh and GABA
Myotonic dystrophy (CTG) - cataracts, toupee, gonadal atrophy
Fragile X (CGG) - chin, Giant Gonads
Friedreich Ataxia (GAA) - ataxic GAAit
77
Q

Genetics of Down syndrome T21

A

Incidence = 1:700
95% due to meiotic non-disjunction (1:1500 in <20yo women, 1:25 if >45yo)
4% due to unbalanced Robertsonian translocation (typically between 14 and 21)
1% due to mosaicism (post-fertilization mitotic error)

78
Q

Pre-natal findings for T21

  • 1st Trimester
  • 2nd Trim
A

1st Trimester:
- US: nuchal lucency, hypoplastic nasal bone
- Serum: decreased PAPP-A, increased free B-hCG
2nd Trimester quad screen:
- low a-fetoprotein, high B-HCG, low estriol, high inhibit A

79
Q

Clinical features of T21 - dysmorphic features

A 
Upslanting palpebral fissures
Epicanthic folds
Brushfield spots
Bradycephaly, flat facial profile/nasal bridge
Low-set/dysplastic ears
Small chin, protruding tongue
Short neck
Single palmar crease, sandal gap
80
Q

Systemic clinical features of T21

A
  • Brain: ID, psych (Autism, disruptive behavioural ds), Alzheimers
  • Heart: AVSD, ASD/PDA, VSD, TOF
  • GIT: duodenal atresia, annular pancreas, Hirschsprung
  • Growth: short stature, obesity
  • Eyes: refractive errors, strabismus, nystagmus
  • Hearing: loss, otitis media
  • Endocrine: Thyroid ds, DM
  • Haem: Leukemias
  • Pulm: OSA and asthma
  • Skin: palmoplanar hyperkeratosis, seborrhoeic dermatitis
81
Q

Serum features of the T21, T18 and neural tube defect

A

a-FP B-hCG estriol inhibin A
T21 low high low high
T18 low low low low
NTD high – – –

82
Q

Features of Edwards syndrome

A 
Trisomy 18
1:8000
PRINCE Edward:
- Prominent occiput, Rocker-bottom feet, ID, Non-disjunction, Clenched-fist (with overlapping fingers), low-set Ears, micrognathia, CHD
Death by 1yo
83
Q

Features of Patau syndrome

A 
Trisomy 13
1:15000
1st Trim: low free B-hCG and low PAPP-A
Severe ID, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydachtyly, cutis aplasia, CHD.
Death by 1yo
84
Q

Describe Robertsonian translocations

  • definition
  • common chromosomes involved
A

Long arms of 2 acrocentric chromosomes fuse at centromere and the 2 short arms are lost
13, 14, 15, 21, 22
Balanced - usually no abn phenotype
Unbalanced - miscarriage, stillbirth or chromo imbalance

85
Q

Genetics of Cri-du-chat syndrome

A

Congenital microdeletion of short arm of chromo 5 (46, XX or XY, 5p-)

86
Q

Clinical features of Cri-du-chat

A

Microcephaly, epicanthic folds, moderate-severe ID, high-pitched crying/meowing, CHDs (VSD)

87
Q

Williams syndrome - genetics and features

A

Congenital microdeletion of long arm of chromo 7 (region includes elastin gene)
Elfin facies, ID, well-developed verbal skills, extreme friendliness to strangers, hypercalcemia (increased sensitivity to Vit D), CVS prob (aortic stenosis)

88
Q

Describe 22q11 deletion syndromes

A

Microdeletion at 22q11 –> aberrant development of 3rd and 4th branchial pouches. AD
CATCH-22
- Cleft palate
- Abn facies
- Thymic aplasia –> T-cell deficiency
- Cardiac defects
- Hypocalcemia (secondary to parathyroid aplasia)

89
Q

2 types of 22q11 deletion syndromes

A

DiGeorge - thymic, parathyroid and cardiac defects

Velocardiofacial - palate, facial and cardiac defects

90
Q

Common cardiac defects in 22q11 deletion

A

Interrupted aortic arch, truncus arteriosus, TOF

91
Q

Functions of vitamin A

A 
Antioxidant
Constituent of retinal pigments
Normal differentiation of epithelial into specialised tissues (eg pancreatic, goblet cells)
Prevents squamous metaplasia
Treats:
- measles
- acute promyelocytic leukemia (all-trans retinoic acid)
- cystic acne (oral isotretinoin)
92
Q

Signs and sx of Vit A deficiency

A 
Night blindness (nyctalopia)
Xerosis cutis 
Keratomalacia
Bitot spots
Immunosuppression
93
Q

Signs of acute Vit A toxicity

A

Nausea and vomiting
Vertigo
Blurred vision

94
Q

Signs of chronic Vit A toxicity

A 
Alopecia
Dry skin (scaliness)
Hepatic toxicity and enlargment
Arthralgias
Pseudotumour cerebri
Teratogenic
95
Q

Thiamine NB for which enzymatic reactions

A

Forms thiamine pyrophosphate (TPP), cofactor in:
Think ATP:
- alpha-ketoglutarate dehydrogenase
- Transketolase
- Pyruvate dehydrogenase
also: Branched chain ketoacid dehydrogenase

96
Q

Diseases of thiamine deficiency

A

Wernicke-Korsakoff

Beri-beri

97
Q

Describe Wernicke-Korsakoff syndrome

  • signs and sx
  • pathology
  • Prevention
  • Dx
A
  • confusion, ophthalmoplegia, ataxia (classic triad), confabulation, personality changes, retrograde and anterograde amnesia
  • damage to medial dorsal nucleus of thalamus
  • prevent by giving thiamine before dextrose in alcoholic/malnourished px
  • increased RBC transketolase activity after giving B1
98
Q

Features of beri-beri

A

Dry beri-beri: polyneuritis, symmetrical muscle wasting

Wet beri-beri: high-output cardiac failure (dilated CMO), edema

99
Q

Functions of Vit B2

A

Riboflavin
Component of FAD and FMN (redox reactions)
B2 = 2ATP.

100
Q

Signs of Vit B2 deficiency

A

“2 C’s of B2”
Cheilosis
Corneal vascularization

101
Q

Functions of Vit B3

A

Niacin - from tryptophan
Constituent of NAD+ and NADP+ (B3 = 3ATP)
Treats dyslipidaemia - lowers VLDL and increases HDL

102
Q

Signs and sx of Vit B3 deficiency

A 
Glossitis
Pellagra (3D's)
- Diarrhoea
- Dementia (also hallucinations)
- Dermatitis (C3/4 dermatome - broad collar rash/casal necklace", hyperpigmentation of sun-exposed limbs
103
Q

Causes of pellagra

A

Hartnup disease
Malignant carcinoid syndrome (increased tryptophan metabolism)
Isoniazid (decreased B6)

104
Q

Pathophysiology of Hartnup disease

A

AR
Deficiency of neutral amino acid (eg tryptophan) transporters in proximal tubule cells and enterocytes –> neutral aminoaciduria and decreased absorption from gut –> decreased tryptophan for conversion to niacin

105
Q

Treatment of Hartnup disease

A

High protein diet and nicotinic acid

106
Q

Signs of niacin excess

A
  • Facial flushing (cx by prostaglandins, avoided by taking aspirin with niacin)
  • Hyperglycemia
  • Hyperuricemia
107
Q

Function of Vit B5

A

Pantothenic acid
B5 = “pento”thenic
Component of CoA and fatty acid synthase

108
Q

Features of Vit B5 deficiency

A

Dermatitis, enteritis, alopecia, adrenal insufficiency

109
Q

Function of Vit B6

A

Pyridoxine
Converted to pyridoxal phosphate (PLP), cofactor in:
- transamination (eg AST/ALT)
- decarboxylation
- glycogen phosphorylase
Synthesis of:
- cystathionine, heme, niacin, histamine, neurotransmitters

110
Q

Signs and sx of pyridoxine deficiency

A

Convulsions, hyperirritability, peripheral neuropathy, sideroblastic anaemias

111
Q

Function of Vit B7

A

Biotin: Co-factor for carboxylation enzymes

  • Pyruvate carboxylase (pyruvate –> oxaloacetate)
  • Acetyl-CoA carboxylase (acetyl-CoA –> malonyl CoA)
  • Propionyl-CoA carboxylase (propionyl-CoA –> methylmalonyl-CoA)
112
Q

Signs of Vit B7 deficiency and causes

A

Dermatitis, alopecia, enteritis
Cx by Ab use or excessive egg white ingestion
“Avidin in egg whites avidly binds biotin”

113
Q

Functions of Vit B9

A

Folate: converted to THF NB for 1-C transfer/methylation

NB for synthesis of nitrogenous bases

114
Q

Folate deficiency results in:

A

Megaloblastic anaemia
Hypersegmented PMN cells
Glossitis
Neural tube defects

115
Q

Drugs that cx folate deficiency

A

Phenytoin, sulfonamides, methotrexate

116
Q

Functions of B12

A

Co-factor for methionine synthase and methymalonyl-CoA mutase

117
Q

Causes of B12 deficiency

A
  • Insufficient intake
  • Malabsorption
  • Lack of intrinsic factor
  • Absence of terminal ileum
118
Q

Functions of Vit C

A
  • Antioxidant
  • Hydroxylation of proline and lysine to preprocollagen
  • Facilitates Fe absorption (by converting to Fe2+)
  • Necessary for conversion of dopamine to NE (dopaine B-hydroxylase)
119
Q

Ancillary treatment of methemoglobinemia

A

Vit C - converts Fe3+ to Fe2+

120
Q

Signs of Vit C deficiency

A 
Scurvy (think poor collagen + bleeding):
- swollen gums
- bruising, petechiae
- hemarthrosis, subperiosteal haem
- corkscrew hair
Also: weakened immune response
121
Q

Sx and signs of Vit C excess

A

N&V, diarrhoea, fatigue
Calcium oxalate nephrolithiasis
Increased risk of iron toxicity in the predisposed

122
Q

Pathologies in Vit D deficiency

A

Rickets, osteomalacia, hypocalcaemic tetany

123
Q

Signs of Vit D excess

A

Hypercalcemia
Hypercalciuria
Loss of appetite
Stupor

124
Q

Vit E deficiency can cx:

A 
Haemolytic anaemia
Acanthocytosis
Neuro signs similar to B12 deficit:
- muscle weakness
- posterior column and spinocerebellar tract demyelination
125
Q

Name of Vit E

A

tocopherol/tocotrienol

126
Q

Functions of Vit K

A

Activated by epoxide reductase to reduced form, co-factor for y-carboxylation of glutamic acid residues on clotting factors: II, VII, IX, X

127
Q

Difference between folate and B12 deficiency in lab findings

A

Both increased homocysteine
Normal methylmalonic acid in folate deficit
Increased for B12 deficit

128
Q

Clotting times seen in Vit K deficiency

A

Eg neonatal haemorrhage

  • Increased PT and aPTT
  • Normal bleeding time
129
Q

Sx and Sn of Zinc deficiency

A 
Delayed wound healing
Hypogonadism
Decreased adult hair
Dysgeusia
Anosmia
Acrodermatitis enteropathica
130
Q

Antidote for methanol/ethylene glycol

A

Fomepizole - inhibits alcohol dehydrogenase

131
Q

5 co-factors that make up pyruvate dehydrogenase complex

A

“The Lovely Co-enzymes For Nerds”

  • Thiamine pyrophosphate (B1)
  • Lipoic acid
  • CoA (B5)
  • FAD (B2)
  • NAD+ (B3)
132
Q

Factors that activate pyruvate dehydrogenase

A

Increased:

  • NAD+/NADH ratio
  • ADP
  • Ca2+
133
Q

Which component of pyruvate dehydrogenase does arsenic inhibit? Clinical findings of arsenic poisoning:

A

Inhibits lipoic acid

- Vomiting, rice-water stools, garlic breath, QT prolongation

134
Q

Pyruvate dehydrogenase deficiency:

  • Findings
  • Treatment
A

Think: pyruvate has to go somewhere =

  • lactic acid(osis)
  • alanine (increased in serum starting in infancy)
  • neurologic defects (low energy)

Rx: Increased ketogenic nutrients (high fat or lysine and leucine) “the onLy pureLy ketogenic aa’s”

135
Q

Electron transport inhibitors in OP:

A

Causes decreased H+ gradient and blocks ATP synthesis:
Complex I: RotenONE
Complex III: An-3-mycin (antimycin) A
Complex IV: CO and cyanide

136
Q

What inhibits ATP synthase?

A

Oligomycin

Cx increased H+ gradient and no ATP synthesis

137
Q

Name 2 uncoupling agents in OP

A

2,4-dinitrophenol (DNP) - illicit weight loss drug

aspirin overdose

138
Q

4 key (irreversible) enzymes in gluconeogenesis

A

“Pathway Produces Fresh Glucose”

  • Pyruvate carboxylase
  • Phosphoenolpyruvate carboxylase
  • Fructose-6-phosphatase
  • Glucose-6-phosphatase
139
Q

Pathophysiology of G6PD deficiency

A

Glucose-6-phosphate provides source of NADPH - reduces glutathione (antioxidant) –> detoxifies radicals and peroxides
Deficiency –> decreased NADPH in RBCs –> haemolytic anaemia (precipitated by infection)
X-linked recessive, most common human enzyme deficiency. Increased malarial resistance

140
Q

What’s seen on blood smear in G6PD deficiency

A
  • Heinz bodies - denatured Hemoglobin precipitates in RBCs
  • Bite cells - phagocytic removal of Heinz bodies
    “Bite into some Heinz ketchup”
141
Q

Outline Essential Fructosuria

A

AR
Defect in fructokinase
Benign, asymptomatic. not trapped in cells. Increased fructose in blood/urine

142
Q

Pathophysiology of Fructose Intolerance

A

AR
Defect in aldolase B
Fructose-1-phosphate accumulates in cells –> reduced phosphate –> inhibits gluconeogen and glycogenolysis

143
Q

Fructose intolerance:

  • sx and sn
  • Dx
  • Rx
A 
Sx present after consuming fructose (honey, juice, fruit):
- hypoglycemia
- jaundice
- cirrhosis
- vomiting
Dx: reducing sugars in urine
Rx: avoid fructose and sucrose
144
Q

Outline galactokinase deficiency

A

AR
Galactosemia and galactosuria
Infantile cataracts

145
Q

Classic galactosemia

  • enzyme deficient
  • genetics
  • signs and sx
A
  • galactose-1-phosphate uridyltransferase
  • AR
  • galactitol accumulates in cells (eg lens of eyes):
  • FTT, jaundice, hepatomegaly, infantile cataracts, ID, predispose to E.coli sepsis
146
Q

Mnemonic for enzymes in fructose and galactose intolerance

A

FAB GUT

Fructose is to Aldolase B as Galactose is to UridylTransferase

147
Q

Cells/tissues that only has aldose reductase (and not sorbitol dehydrogenase)

A 
NB because sorbitol dehyd converts sorbitol to fructose (used as energy) but sorbitol trapped in cells cx osmotic damage (seen in DM):
- Lens (primarily aldose reductase)
- Retina 
- Kidneys
- Schwann cells
"LuRKS"
148
Q

Tests for lactose intolerance

A 
Stool = decreased pH
Breath = increased hydrogen content (lactose hydrogen breath test)
149
Q

Essential amino acids

A 
Glucogenic:
"I MEt HIS VALentine, she is so sweet"
- Methionine
- Histidine
- Valine
Glucogenic/ketogenic:
- Isoleucine
- phenyalanine
- threonine
- tryptophan
Ketogenic
- leucine
- lysine
150
Q

Acidic amino acids

A

Aspartic acid

Glutamic acid

151
Q

Basic amino acids

A

“HIS Lys (lies) ARe basic”

  • Histidine
  • Lysine
  • Arginine
152
Q

Treatment given for hypoammonemia

A
  • lactulose: acidifies GIT and traps NH4+ for excretion
  • antibiotics (eg rifaximin): decrease colonic ammoniagenic bacteria
  • benzoate, phenyacetate and phenylbutyrate - reacts with glycine/glutamine –> renal excretion
153
Q

What does a picture of decreased BUN, increased orotic acid (blood and urine) and hypoammonemia suggest? Describe the condition

A

Ornithine transcarbamylase deficiency

  • X-linked recessive
  • Excessive carbamoyl phosphate converted to orotic acid
154
Q

Describe phenylketonuria

  • genetics
  • pathophysiology
A

AR, 1:10000
Defect in phenylalanine hydroxylase or tetrahydrobiopterin (BH4) cofactor –> increased phenylalanine –> increased phenyl ketones in urine

155
Q

What are the phenyl ketones

A

phenylacetate
phenyllactate
phenylbutyrate

156
Q

Signs and sx of phenyketonuria

A 
ID (think dopamine comes from phenylalanine)
Growth retardation
Seizures
Fair skin
Eczema
musty skin odor
157
Q

Pathophysiology of Maple syrup urine disease

A

AR
Decreased branched-chain alpha-ketoacid dehydrogenase –> blocked degradation of branched chain aa’s (isoleucine, leucine, valine) –> severe ID, CNS defects, death
“I Love Vermont maple syrup from maple trees (B1ranches)”

158
Q

Presentation and Rx of maple syrup urine ds

A

Vomiting, poor feeding, urine smells like maple syrup

Rx: restrict branched chain aa’s and thiamine supplementation

159
Q

What to think about when px has blue sclera

A

Osteogenesis imperfecta

alkaptonuria

160
Q

Describe alkaptonuria

  • enzyme deficit
  • genetics
  • findings
A
  • homogentisate oxidase (degrades tyrosine to fumarate)
  • -> pigment forming homogentisic acid accumulates in tissue
  • AR
  • bluish-black CT, ear cartilage and sclera (ochronosis); urine turns black in prolonged exposure to air, debilitating arthralgias
161
Q

3 types of homocysteinuria and their Rx

A
  • cystathionine synthase deficiency: decrease methionine, increase cysteine, B6, B12 and folate in diet
  • decreased affinity of cystathionine synthase for pyridoxal phosphate: high B6 intake, increase cysteine
  • methionine synthase deficiency: increase methionine in diet
162
Q

Findings in homocysteinuria

A

HOMOCYstinuria:

  • Homocysteinura
  • Osteoporosis
  • Marfanoid features
  • Ocular changes (lens displace inward and downward)
  • CVS: MI and strokes
  • kYphosis
  • ID
163
Q

A positive urinary cyanide-nitroprusside test indicates:

A

Cystinuria

164
Q

Describe cystinuria

A

-AR (1:7000)
- Inability of PCT to reabsorb COLA: cystine, ornithine, lysine, and arginine
- precipitation of hexagonal cystine stones
Rx by urinary alkalinization (K citrate), chelating agents (penicillamine), good hydration

165
Q

4 NB types of glycogen storage diseases and their deficit enzymes

A

“Very Poor Carbohydrate Metabolism”

  • Von-Gierke disease (type I) - glucose-6-phosphatase
  • Pompe disease (typeII) - lysosomal acid a-1,4-glucosidase
  • Cori disease (type III) - a-1,6-glucosidase
  • McArdle (type V) - myophosphorylase
166
Q

Which glycogen storage disease affects mainly the heart

A

“PomPe trashes the PumP (1,4)”

- cardiomegaly, HCOM, hypotonia, exercise intolerance

167
Q

Difference between Von Gierke and Cori disease

A

Different enzymes

Gluconeogenesis intact in Cori

168
Q

Which glycogen storage disease mainly affects muscles

A

McArdle = muscle

muscle cramps, myoglobinuria, arrhythmias

169
Q

Difference between Tay-Sachs and Niemann-Pick disease

A
  • HeXosaminidase A (TAy-SaX) vs sphingomyelinase “No man picks his nose with his sphinger”
  • No hepatosplenomeg in Tay-Sachs; foam cells in NP
  • Both have progressive neurodegen, cherry-red spot in macula
170
Q

Triad of Fabry disease

A
  • Episodic peripheral neuropathy, angiokeratomas, hypohidrosis
  • Late: progressive renal failure, CVS disease
171
Q

Which lysosomal storage disease affects oligodendrocytes

A

Krabbe disease
Cx periph neuropathy, developmental delay, optic atrophy
Globoid cells

172
Q

List of sphingolipidoses

A
  • Tay-Sachs
  • Fabry
  • Metachromatic leukodystrophy
  • Krabbe disease
  • Gaucher
  • Niemann-Pick
173
Q

Findings of hepatosplenomeg, pancytopenia, osteoporosis, avascular necrosis of femur, developmental delay, optic atrophy suggests:

A

Gaucher disease

Deficient glucocerebrosidase

174
Q

2 types of mucopolysaccharidoses

A

Hurler syndrome - a-L-iduronidase

Hunter syndrome - iduronate sulfatase

175
Q

Findings in Hurler syndrome

A

Previously called gargoylism, developmental delay, airway obstruct, hepatosplenomeg, corneal clouding

176
Q

Findings in Hunter syndrome

A

“Hunter sees clearly (no corneal clouding) and aggressively aim (aggressive behaviour) for the X (X-linked recessive).”

177
Q

Increased incidence of what lysosomal storage diseases in Ashkenazi Jews?

A
  • Tay-Sachs, Niemann-Pick, some Gaucher
178
Q

Hypoketotic hypoglycemia can be caused by:

A
  • Systemic primary carnitine deficiency

- Medium-chain acyl-CoA dehydrogenase deficiency

179
Q

Pathophysiology of abetalipoproteinemia

A
  • AR

- Deficient ApoB48 and ApoB100 - no chylomicrons, LDL or VLDL

180
Q

Findings in and Rx of abetalipoproteinemia

A

Early: severe fat malabsorption, steatorrhoea, FTT
Later: retinitis pigmentosa, spinocerebellar degen (Vit E deficiency), progressive ataxia, acanthocytosis

Rx: restrict intake of long-chain FAs, high dose oral Vit E

181
Q

4 types of familial dyslipidaemias

A
  • Type I - familial hyperchylomicronemia: AR, deficit LPL or apoCII –> high chylomicrons –> pancreatitis, HSM, eruptive xanthomas
  • Type II - familial hypercholesterolemia: AD, deficit LDL receptors –> increased LDL and cholesterol –> accelerated atherosclerosis, tendon xanthomas, corneal arcus
  • Type III - dysbetalipoproteinemia: AR, deficit ApoE –> increased chylomicrons and VLDL –> premature atherosclerosis, xanthomas
  • Type IV - hypertriglyceridemia: AD, hepatic overproduction of VLDL –> increased VLDL and TG –> acute pancreatitis
182
Q

NB amino acids needed for synth of:

  • nitric oxide
  • urea
  • heme
  • creatinine
A
  • arginine
  • arginine and aspartate
  • glycine and succinyl-CoA
  • glycine + arginine + SAM
183
Q

Glutamate is NB for synthesis of:

A

GABA and glutathione

184
Q

NB amino acids for synth of:

  • purines
  • pyrimidines
  • histamine
A
  • glutamine, aspartate, glycine
  • glutamnine, aspartate
  • histidine
185
Q

Tyrosine is precursor of:

A 
Dopamine 
Norepinephrine
Epinephrine
Thyroxine
Melanin
186
Q

Tryptophan is precursor of:

A

Serotonin
Melatonin
Niacin

USMLE Step 1 (11 decks)

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