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Biochemistry Flashcards

1
Q

DNA methylation at CpG islands - Methyltransferase using SAM.

in euk, cytosine-guanine dinucleotide repeats in the promoter region of genes are preferentially methylated as part of the epigenetic code

A

Represses transcription of those genes

Note - Mechanism of imprinting.

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2
Q

Histone methylation.

Note - H1 is linker histone

A

Usually reversibly represses DNA transcription

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3
Q

Histone acetylation.

A

Relaxes coiling and allows for transcription

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4
Q

Amino acids necessary for de novo purine synthesis - Conversion of PRPP to IMP

A

Glycine
Aspartate
Glutamine

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5
Q

Required for Pyrimidine base production.

A

Aspartate

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6
Q

Reduced degradation of Adenosine and Deoxyadenosine to Inosine/Hypoxanthine - Increased dATP and toxicity in lymphocytes.

A

ADENOSINE DEAMINASE (ADA) DEFICIENCY

One of the major causes of autosomal recessive SCID.

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7
Q

Defective purine salvage due to absent HGPRT - Converts Hypoxanthine to IMP / Guanine to GMP.

Results in increased Uric Acid/Purine synthesis

A

LESCH-NYHAN SYNDROME

X-linked recessive.

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8
Q

Symptoms of Lesch-Nyhan syndrome.

A 
Hyperuricemia (orange "sand" sodium urate crystals in diaper)
Gout
Pissed off (aggression, self-mutilation)
Retardation
dysTonia

Treat with Allopurinol or Febuxostat

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9
Q

5’ - 3’ / 3’ - 5’ exonuclease activity for removal of RNA primers and damaged DNA

A

DNA POL I

Prokaryotes only

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10
Q

5’ - 3’ synthesis with 3’ - 5’ exonuclease activity for proofreading

A

DNA POL III

Prokaryotes only

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11
Q

RNA-dependent DNA-pol (reverse transcriptase) adds DNA (TTAGGG) to 3’ end of lagging template strand - end replication problem

A

TELOMERASE

Eukaryotes only - dysregulated in cancer cells allowing for unlimited replication.

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12
Q

Substitution of glutamic acid with valine (missense mutation).

A

Sickle Cell Disease

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13
Q

Nucleotide substitution resulting in early stop codon and usually a nonfunctional protein.

A

Nonsense mutation

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14
Q

Deletion or insertion of a number of nucleotides not divisible by 3 resulting in misreading of all nucleotides downstream (frameshift).

A

Duchenne Muscular Dystrophy

Tay-Sachs Disease

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15
Q

LAC operon activation in presence of low glucose and high lactose.

A

Increased adenylate cyclase activity
Increased generation of cAMP from ATP
Activation of catabolite activator protein (CAP)

Unbinding of repressor protein from repressor/operator site

Both result in increased transcription

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16
Q

Defective nucleotide excision repair (G1) preventing repair of pyrimidine dimers secondary to UV exposure.

A

Xeroderma Pigmentosum

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17
Q

Removal of altered base and creation of AP site with glycosylate for AP-endonuclease (throughout cell cycle).

A

Base excision repair (spontaneous/toxic deamination)

Note - Endonuclease cleaves 5’ end and lyase cleaves 3’ sugar-phosphate

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18
Q

Defective mismatch repair (G2).

A

Lynch Syndrome (HNPCC)

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19
Q

Defective nonhomologous end joining for double-stranded breaks.

A

Ataxia Telangiectasia

Fanconi Anemia

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20
Q

Modified 3’ OH preventing addition of next nucleotide containing 5’ triphosphate.

A

CHAIN TERMINATION

DNA replication blocking drugs

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21
Q

Inhibits RNA polymerase II causing hepatotoxicity.

A

Alpha-amanitin (Amanita Phalloides)

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22
Q

Inhibition both prokaryotic and eukaryotic RNA pol.

A

Actinomycin D

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23
Q

Antibodies to spliceosomal snRNPs (Lariat loop).

A

ANTI-SMITH

Specific for SLE.

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24
Q

Antibodies to U1 RNP.

A

Mixed connective tissue disease

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25
Q

Contains sequence necessary for tRNA-ribosome binding.

A

T-arm

Molecule is a loop with 5’ end base paired to 3’ end - 3’ end contains CCA acceptor stem

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26
Q

Necessary for tRNA recognition by correct aminoacyl-tRNA synthetase (ATP-dependent).

A

D-arm

Malfunction in results in mischarged tRNA (right codon, wrong amino acid).

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27
Q

Steps of eukaryotic protein synthesis (GTP-dependent).

A

Initiation: tRNA-Met binds to P site of 40s to recruit 60s (80s total).

Elongation: tRNA binds A site, rRNA transfers polypeptide to amino acid on A site, ribosome advances 5’ to 3’ moving new tRNA to P site and old tRNA to E site.

Termination: Stop codon recognized by releasing factor adding water instead of AA to growing polypeptide.

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28
Q

Inhibition of G1-S progression.

A

p53 induces p21
Inhibition of CDK
Hypophosphorylated Rb inactivates E2F (transcription factor)

Mutation results in Li-Fraumeni Syndrome.

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29
Q

Permanent cell types (remain in G0) - regenerate from stem cells only.

A

Neurons
Skeletal and Cardiac muscle
RBCs

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30
Q

Stable (quiescent) cell types - must be stimulated to enter G1.

A

Hepatocytes

Lymphocytes

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31
Q

Rich in RER.

A

Mucus-secreting goblet cells

Plasma cells

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32
Q

Rich in SER (steroid synthesis, detoxification).

A

Hepatocytes

Steroid producing cells (adrenal cortex, gonads)

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33
Q

Coarse facial features
Clouded corneas
Restricted joint movement
High plasma levels of lysosomal enzymes

A

I-CELL DISEASE

Defect in N-acetylglucosaminyl-1-phosphotransferase
Failure of golgi to phosphorylate mannose residues
Proteins secreted extracellularly instead of to lysosomes

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34
Q

Absent or dysfunctional SRP.

A

Protein accumulation in the cytosol (traffic protein from ribosome to RER).

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35
Q

Traffic proteins from cis-Golgi back towards ER.

A

COPI

COPII transports from ER to cis-Golgi.

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36
Q

Traffic proteins from trans-Golgi to lysosomes, or plasma membrane to endosomes.

A

Clathrin

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37
Q

Vimentin stain.

A

MESENCHYME - FIBROBLASTS, ENDOTHELIAL, MACROPHAGES

Sarcoma
Endometrial carcinoma
Renal cell carcinoma
Meningioma

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38
Q

Desmin stain.

A

MUSCLE

Rhabdomyosarcoma

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39
Q

Cytokeratin stain.

A

EPITHELIUM

Epithelial tumors (e.g. SCC)

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40
Q

GFAP (glial fibrillary acid protein) stain.

A

NEUROGLIA (ASTROCYTES, SCHWANN, OLIGODENDROGLIA)

Astrocytoma
Glioblastoma

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41
Q

Neurofilament stain.

A

NEURONS

Neuronal tumors (neuroblastoma)

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42
Q

Drugs that act on microtubules.

A

(Microtubules Get Constructed Very Poorly)

Mebendazole
Griseofulvin
Colchicine
Vincristine
Paclitaxel
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43
Q 
Infertility (M/F)
Ectopic pregnancy
Bronchiectasis
Recurrent sinusitis
Situs inversus (dextrocardia)
A

KARTAGENER SYNDROME (PRIMARY CILIARY DYSKINESIA)

Autosomal recessive

Dynein mutation leading to immotile cilia

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44
Q

Type I collagen (90%).

A 
Bone
Skin
Tendon
Fascia
Cornea
Late wound repair (> 3 wks)
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45
Q

Type II collagen.

A

Cartilage
Vitreous body
Nucleus pulposus

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46
Q

Type III collagen.

A

Reticulin (viscera, marrow)
Blood vessels/lymphatics
Granulation tissue (< 3 wks)

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47
Q

Type IV collagen.

A

Basement membrane
Basal lamina
Lens

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48
Q

Collagen synthesis.

A

Synthesis of preprocollagen - Mostly Glycine
Hydroxylation of Proline/Lysine (requires Vit C)
Glycosylation / triple helix formation via disulfide bonds
From ER to Golgi
Exocytosis of procollagen
Cleavage of procollagen C/N terminals forming insoluble tropocollagen
Covalent cross-linking of staggered tropocollagen via lysyl oxidase (acts on lysine)
Formation of fibrils

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49
Q

Multiple fractures with minimal trauma
Blue sclera
Hearing loss
Tooth abnormalities (dentin)

A

OSTEOGENESIS IMPERFECTA

Autosomal dominant (COL1A1/2)

Defect in triple helix formation of Type I collagen.

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50
Q 
Hypermobile joints
Joint dislocation
Hyperextensible skin
Easy bruising and bleeding
(Berry and Aortic aneurysms)
A

EHLERS-DANLOS SYNDROME

Type V collagen defect - Procollagen Peptidase or Lysyl Hydroxylase

Note - Forms soluble collagen that cannot cross-link

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51
Q

Brittle, lanky hair
Growth retardation
Hypotonia

A

MENKES DISEASE

X-linked recessive (ATP7A).

Defect in copper absorption - Decreased activity of Lysyl Oxidase and thus covalent cross-linking.

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52
Q 
Tall with long extremities
Arachnodactyly
Hypermobile joints
Cystic medial necrosis of aorta (aortic dissection)
Mitral valve prolapse
Subluxation of lenses (upwards)
A

MARFAN SYNDROME

Autosomal dominant
Fibrillin FBN1 (glycoprotein sheath around elastin) on Chromosome 15
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53
Q

Elastin synthesis.

A

Tropoelastin
Proline/Lysine remain non-hydroxylated
Excretion into ECM and interaction with fibrillin scaffold
Lysyl oxidase (requires Cu) forms Desmosine cross-links on Lysine - gives elastic properties

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54
Q

Blotting procedures.

A 
Northern = RNA
Southern = DNA
Western = Protein (confirmatory for HIV after ELISA)
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55
Q

Used to compare gene expression levels of thousands of genes between two samples.

A

Microarray

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56
Q

Used to assess size and protein expression of individual cells in a sample.

A

Flow cytometry

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57
Q

Used to detect the presence of a specific antigen or antibody in a blood sample.

A

ELISA

Note - Unlike Western blot the serum is tested directly

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58
Q

Inheritance of mutation in tumor suppressor gene requires complementary allele to be mutated before cancer develops.

A

LOSS OF HETEROZYGOSITY

E.g. Retinoblastoma, HNPCC, Li-Fraumeni

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59
Q

Heterozygote producing a nonfunctional protein that also prevents function of normal protein.

A

Dominant negative mutation

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60
Q

Cafe-au-lait spots
Polyostotic fibrous dysplasia
Precocious puberty

A

MCCUNE-ALBRIGHT SYNDROME

Mutation in G-protein signaling - only survivable if somatic mosaicism.

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61
Q

Mutations at different loci produce the same phenotype.

A

LOCUS HETEROGENEITY

E.g. Albinism

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62
Q

Different mutations in the same locus produce the same phenotype.

A

ALLELIC HETEROGENEITY

E.g. B-Thalassemia

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63
Q

Individual manifesting a recessive disorder when only one parent is a carrier.

A

UNIPARENTAL DISOMY

Euploid.

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64
Q

Hardy-Weinberg equilibrium

A

p2+2pq+q2

X-linked recessive in males = p
X-linked recessive in females = p2

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65
Q 
Intellectual disability
Hyperphagia
Obesity
Hypogonadism
Hypotonia
A

PRADER-WILLI SYNDROME

most commonly due to microdeletions involving the PATERNAL chromosome 15q11-13 region or maternal uniparental disomy
OR
Maternal imprinting on chromosome 15 - Father mutated

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66
Q

Intellectual disability
Inappropriate laughter
Seizures
Ataxia

A

ANGELMAN SYNDROME

Parental imprinting on chromosome 15 - Maternal gene mutated

Loss of maternally inherited allele from chromosome 15. Due to MATERNAL microdeletion or paternal uniparental disomy.

Note - Occasionally paternal uniparental disomy

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67
Q

Bone pain and skeletal abnormalities due to increased phosphate wasting at proximal tubules.

A

HYPOPHOSPHATEMIC (VIT D RESISTANT) RICKETS

X-linked dominant

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68
Q 
Autism
Large ears
Long face with large jaw
Macroorchidism
Hypotonia
Hyperextensible fingers
Mitral valve prolapse
A

FRAGILE X SYNDROME

X-linked dominant
CGG repeat in FMR1 gene resulting in methylation

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69
Q

Constitutive action of fibroblast growth factor receptor 3 (FGFR3) inhibits chondrocyte proliferation and thus endochondral ossification.

A

ACHONDROPLASIA

Autosomal dominant
Full penetrance
Chromosome 4 ("4 short limbs")
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70
Q

Bilateral massive enlargement of kidneys due to mutation in PKD1 on chromosome 16.

A

ADPKD

Autosomal dominant
Chromosome 16 ("16 letters in polycystic kidney")
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71
Q

Numerous adenomatous polyps following puberty.

A

FAMILIAL ADENOMATOUS POLYPOSIS

Autosomal dominant
APC gene on Chromosome 5q (“5 letters in polyp”)

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72
Q 
Telangiectasias
Recurrent epistaxis
AVM
GI bleeding
Hematuria
A

HEREDITARY HEMORRHAGIC TELANGIECTASIA (OSLER-WEBER-RENDU)

Autosomal dominant

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73
Q

Spheroid erythrocytes due to spectrin or ankyrin defect.

Elevated MCHC
Elevated RDW

A

HEREDITARY SPHEROCYTOSIS

Autosomal dominant

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74
Q

Depression
Progressive dementia
Choreiform movements
Caudate atrophy

Elevated dopamine
Decreased GABA
Decreased Ach

A

HUNTINGTON DISEASE

Autosomal dominant
CAG repeat on Chromosome 4

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75
Q

Multiple malignancies at an early age

SBLA - Sarcoma, Breast, Lung, Adrenal

A

LI-FRAUMENI SYNDROME

Autosomal dominant
Mutation in TP53

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76
Q 
Cafe-au-lait spots
Cutaneous neurofibromas
Optic gliomas
Lisch nodules (iris)
Pheochromocytoma
A

NEUROFIBROMATOSIS TYPE 1 (VON RECKLINGHAUSEN)

Autosomal dominant
Full penetrance with variable expression
NF1 gene on Chromosome 17 (“17 letters in von recklinghausen”)

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77
Q

Bilateral acoustic schwannomas
Juvenile cataracts
Meningiomas
Ependymomas

A

NEUROFIBROMATOSIS TYPE 2

Autosomal dominant
NF2 gene on Chromosome 22 (“type 2 = 22”)

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78
Q

Cerebellar hemangioblastomas
Clear cell RCC
Pheochromocytoma

A

VON HIPPEL-LINDAU DISEASE

VHL tumor suppressor gene deletion on Chromosome 3 (“3 words in von hippel-lindau”)

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79
Q

Autosomal recessive disorders.

A

ENZYME DEFICIENCIES

Except Hunter’s, Fabry, OTC (X-linked recessive).

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80
Q

Recurrent pulmonary infections (s. aureus, pseudomonas)
Nasal polyps
Chronic bronchitis and bronchiectasis (reticulonodular)
Pancreatic insufficiency/exocrine atrophy
Meconium ileus
Biliary cirrhosis
Infertility in men (absent vas deferens)
Subfertility in women (thick cervical mucous)
Nail clubbing

A

CYSTIC FIBROSIS

Autosomal recessive
CFTR gene on chromosome 7 - ATP-gated Cl channel

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81
Q

Management of cystic fibrosis.

A

Confirm with…
Sweat Cl > 60
Negative transepithelial potential difference
Elevated immunoreactive trypsinogen (newborn screen)

Lumacaftor/Ivacaftor to increase membrane channels
Chest physiotherapy
Albuterol
Dornase alfa (DNAse)
Hypertonic saline
Azithromycin (anti-inflammatory)
Pancreatic enzymes
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82
Q

Pathophysiology of dF508 cystic fibrosis.

A

ATP-gated Cl channel misfolded and degraded
Cl channels reaching the membrane are dysfunctional
Decreased Cl secretion (in to out channel)
Compensatory Na/water reabsorption
Abnormally thick mucus in lungs and GI tract

Hyponatremia (NaCl lost in sweat; out to in channel)
Low ECF Na/water leads to renal K/H wasting
Contraction alkalosis (like loop diuretic)
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83
Q

Common X-linked recessive disorders

(“Be Wise Fools GOLD Heeds Hope”)

Note - Paternal to son transmission does not occur

A 
Bruton agammaglobulinemia
Wiskott-Aldrich syndrome
Fabry disease
G6PD deficiency
OTC deficiency
Lesch-Nyhan
Dystrophy (muscular)
Hunter syndrome
Hemophilia
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84
Q 
Pelvic girdle weakness
Waddling gait < 5 y/o
Gower's maneuver
Calf pseudohypertrophy (fibrofatty replacement)
Dilated cardiomyopathy (mortality)

Elevated CK and aldolase

A

DUCHENNE MUSCULAR DYSTROPHY

X-linked recessive frameshift mutation resulting in truncated dystrophin (links ECM to actin) and thus myonecrosis.

Confirm with biopsy/western blot.

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85
Q

Myopathy
Lactic acidosis
CNS disease

Ragged red fibers on muscle biopsy

A

MITOCHONDRIAL MYOPATHIES

Transmitted only through the mother with heteroplasmy (variable expression).

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86
Q

Pelvic girdle weakness with onset in adolescence.

A

BECKER MUSCULAR DYSTROPHY

X-linked recessive non-frameshift insertion in dystrophin gene (partially functional).

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87
Q 
Myotonia (endless grip)
Muscle wasting
Cataracts
Testicular atrophy
Frontal balding
Arrhythmia
A

MYOTONIC DYSTROPHY TYPE 1

Autosomal dominant
CTG repeat in myotonin protein kinase (DMPK) gene

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88
Q

Trinucleotide repeat expansion diseases.

“X-Girlfriend’s, First Aid, Helped Ace, My Test”

A 
Fragile X (CG-)
Friedreich ataxia (GA-)
Huntington disease (CA-)
Myotonic dystrophy (CT-)
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3
4
5
Perfectly
89
Q 
Intellectual disability
Flat facies
Epicanthal folds
Single palmar crease
Duodenal atresia
Hirschsprung's disease
AV septal defect, ASD, VSD
Early-onset Alzheimer's
ALL and AML
A

DOWN’S SYNDROME (TRISOMY 21)

1st trimester:
Increased nuchal translucency
Increased b-hCG
Decreased PAPP-A

2nd trimester:
Increased b-hCG
Increased inhibin A
Decreased a-fetoprotein
Decreased estriol
90
Q 
Severe intellectual disability
Rocker-bottom feet
Micrognathia
Low-set ears
Clenched hands with overlapping fingers
Congenital heart disease
A

EDWARDS SYNDROME (TRISOMY 18)

1st trimester:
Decreased b-hCG
Decreased PAPP-A

2nd trimester:
Decreased b-hCG
Decreased or normal inhibin A
Decreased a-fetoprotein
Decreased estriol
91
Q 
Severe intellectual disability
Rocker-bottom feet
Microcephaly
Cleft lip and palate
Holoprosencephaly
Polydactyly
Congenital heart disease
Omphaloceles
A

PATAU SYNDROME (TRISOMY 13)

1st trimester:
Decreased b-hCG
Decreased PAPP-A

92
Q 
Intellectual disability
Microcephaly
High pitched crying
Epicanthal folds
Cardiac abnormalities (VSD)
A

CRI-DU-CHAT SYNDROME

Congenital microdeletion of short arm of Chromosome 5

93
Q 
Intellectual disability
Elfin facies
Extreme friendliness
Well-developed verbal skills
Hypercalcemia
Cardiovascular problems (supravalvular aortic stenosis)
A

WILLIAMS SYNDROME

Congenital microdeletion of long arm of Chromosome 7

94
Q 
Cleft palate
Abnormal facies
Thymic aplasia
Cardiac defects (truncus, TOF)
Hypocalcemia
A

22q11 DELETION SYNDROMES

Failed neural crest migration - Aberrant development of 3rd/4th branchial pouches

DiGeorge syndrome - Thymic, Parathyroid, and Cardiac
Velocardiofacial syndrome - Palate, Facial, and Cardiac

Note - Detected with FISH

95
Q

Fat soluble vitamins.

A

A, D, E, K

Absorption dependent on gut and pancreas.

96
Q 
Vitamin deficiency resulting in...
Night blindness
Infections
Squamous metaplasia to keratinizing epithelium
Corneal degeneration
Conjunctival spots
A

VITAMIN A (RETINOL) DEFICIENCY

97
Q

Vitamin toxicity resulting in…

Acutely - N/V, Vertigo, Blurred vision

Chronically - Alopecia, Dry Skin, Transaminitis, Pseudotumor Cerebri, Arthralgia

Note - Also Teratogenic

A

VITAMIN A (RETINOL) TOXICITY

98
Q

Vitamin deficiency resulting in…

Polyneuritis with muscle wasting - Dry beriberi
Dilated cardiomyopathy and HFpEF - Wet beriberi

A

VITAMIN B1 (THIAMINE) DEFICIENCY

a-Ketoglutarate/Pyruvate Dehydrogenase dysfunction - Impaired glucose breakdown leads to ATP depletion worsened by glucose infusion

Diagnosed by increased RBC Transketolase activity following B1 administration - Transketolase used in non-oxidative step of HMP shunt

99
Q

Vitamin deficiency resulting in…

Cheilosis
Stomatitis
Glossitis
Seborrheic dermatitis
Corneal calcification
A

VITAMIN B2 (RIBOFLAVIN) DEFICIENCY

Generates FAD/FMN

Needed for…
ETC
Succinate Dehydrogenase (TCA)

100
Q

Vitamin deficiency resulting in…

Diarrhea
Dementia
Dermatitis (collar rash, hyperpigmented limbs)

A

VITAMIN B3 (NIACIN) DEFICIENCY

Generates NAD

Needed for…
Isocitrate dehydrogenase
a-ketoglutarate dehydrogenase
Malate dehydrogenase

101
Q

Causes of B3 deficiency

A

Hartnup disease

Malignant Carcinoid - Increased tryptophan catabolism

Isoniazid

102
Q

Mechanism of Hartnup disease

A

Autosomal recessive deficiency of neutral amino acid transporters in kidneys and gut

Neutral aminoaciduria and decreased absorption

Decreased tryptophan for conversion to Niacin

Treat with high protein diet and Nicotinic Acid

103
Q

Facial flushing caused by prostaglandins
Hyperglycemia
Hyperuricemia

Used to lower VLDL and raise HDL

A

VITAMIN B3 TOXICITY

Note - Can treat flushing with ASA

104
Q

Vitamin deficiency resulting in…

Dermatitis
Enteritis
Alopecia
Adrenal insufficiency

A

VITAMIN B5 (PANTOTHENIC ACID) DEFICIENCY

Generates CoA

105
Q

Vitamin deficiency resulting in…

Cheilosis, stomatitis, glossitis
CNS abnormalities (neurotransmitter deficiency)
Peripheral neuropathy (with Isoniazid, OCP)
Sideroblastic anemia (impaired hemoglobin synthesis)
A

VITAMIN B6 (PYRIDOXINE) DEFICIENCY

Generates PLP

Needed for…
Transamination

106
Q

Vitamin deficiency resulting in…

Dermatitis
Enteritis
Alopecia
Metabolic acidosis

Note - In the setting of excess ingestion of raw egg whites

A

VITAMIN B7 (BIOTIN) DEFICIENCY

Needed for…
Carboxylation reactions

107
Q

Vitamin deficiency resulting in…

Macrocytic megaloblastic anemia
Hypersegmented PMN
Glossitis
Increased homocysteine
Normal methylmalonic acid

Note - In the setting of alcoholism and pregnancy

A

VITAMIN B9 (FOLATE) DEFICIENCY

Generates THF

Needed for…
DNA/RNA base synthesis

Note - Absorbed in jejunum

108
Q

Vitamin deficiency resulting in…

Macrocytic megaloblastic anemia
Hypersegmented PMN
Paresthesias
Subacute combined degeneration
Increased homocysteine
Increased methylmalonic acid (neurotoxic)

Note - Deficiency takes years

A

VITAMIN B12 (COBALAMIN) DEFICIENCY

Needed for…
DNA synthesis

Note - Absorbed in ileum

109
Q

Causes of Vitamin B12 (Cobalamin) deficiency

A 
Malabsorption
Pernicious anemia (IF antibodies)
Gastric bypass (lack of IF)
Resection of terminal ileum
Veganism
110
Q

Vitamin deficiency resulting in…

Swollen gums
Bruising/Petechiae
Poor wound healing
Corkscrew hair
Myalgia
Hemarthrosis
Anemia
Immunosuppression
A

VITAMIN C (ASCORBIC ACID) DEFICIENCY (SCURVY)

Antioxidant activity reduces iron to Fe2+ for absorption

111
Q

Vitamin C (Ascorbic acid) toxicity.

Cholecalciferol in milk/skin
Calcifediol (25-OH) in storage
Calcitriol (1,25-OH) in active form

A 
Nausea/Vomiting
Diarrhea
Fatigue
Calcium oxalate nephrolithiasis
Iron toxicity in hemochromatosis
112
Q

Vitamin deficiency resulting in…

Bone pain
Deformity in children
Osteomalacia/muscle weakness in adults
Hypocalcemic tetany

A

VITAMIN D DEFICIENCY

113
Q

Vitamin D toxicity

A

Hypercalcemia
Hypercalciuria
Loss of appetite
Stupor

114
Q

Vitamin deficiency resulting in…

Hemolytic anemia (oxidative damage)
Neuromuscular disease (Vit B12-like damage)
Acanthocytes (spur cells)
Infertility

A

VITAMIN E DEFICIENCY

115
Q

Vitamin deficiency resulting in…

Neonatal hemorrhage
Increased PT/PTT
Normal bleeding time

Note - Synthesized by intestinal flora

A

VITAMIN K DEFICIENCY

116
Q

Vitamin K dependent clotting factors (inhibited by Warfarin)

A

II, VII, IX, X, and C/S

117
Q

Deficiency resulting in…

Delayed wound healing
Hypogonadism
Decreased adult hair
Dysgeusia (metallic taste)
Anosmia
Acrodermatitis enteropathica (dermatitis/alopecia around orifices)
A

ZINC DEFICIENCY

118
Q

Protein malnutrition resulting in a small child with a swollen abdomen…

Malnutrition
Edema (decreased plasma oncotic pressure)
Anemia
Liver (fatty changes, decreased Apo synthesis)

A

KWASHIORKOR

119
Q

Total calorie malnutrition resulting in emaciation (tissue and muscle wasting, loss of subQ fat).

A

MARASMUS

120
Q

Antidote for methanol or ethylene glycol poisoning.

A

FOMEPIZOLE

Inhibits alcohol dehydrogenase preventing buildup of acetaldehyde.

121
Q

Treatment for alcoholism by worsening hangover symptoms.

A

DISULFIRAM

Inhibits acetaldehyde dehydrogenase allowing for accumulation of acetaldehyde.

122
Q

Metabolic effects of increased NADH/NAD ratio (chronic alcoholism).

A

Lactic acidosis (Pyruvate to Lactate)

Fasting hypoglycemia (Less Oxaloacetate prevents gluconeogenesis)

Hepatosteatosis (shunting of DHAP to Glycerol/TG production)

Ketoacidosis (inhibition of TCA shunting Acetyl-CoA to Ketogenesis)

123
Q

Pentose phosphate pathway (HMP shunt) products (2) and their use

A

NADPH (oxidative, irreversible):
Steroids, Cholesterol, FFA synthesis

Ribose-5-Phosphate (nonoxidative, reversible):
Nucleotide synthesis

Note - NADPH also required for oxidative burst

124
Q

First committed step of glycolysis.

A

GLUCOSE + ATP = GLUCOSE-6-P

Low concentrations:
Via Hexokinase in tissues (high affinity, low capacity) - Feedback inhibited by Glucose-6-Phosphate.

High concentrations/Presence of insulin:
Via Glucokinase in liver/pancreas (low affinity, high capacity) - Feedback inhibited by Fructose-6-Phosphate.

Note - Mutation in Glucokinase responsible for MODY (responsible for glucose sensing in beta cells)

125
Q

Rate limiting step of glycolysis.

A

FRUCTOSE-6-P + ATP = FRUCTOSE-1,6-BP

By Phosphofructokinase-1
Feedback inhibited by ATP and Citrate
Feedback activated by AMP and F-2,6-BP

126
Q

Reversible production of ATP.

Note - Erythrocytes bypass this step in order to produce 2,3-BPG (no ATP)

A

1,3-BPG = 3-PG + ATP

By Phosphoglycerate kinase

Note - Production of 1,3-BPG requires NAD

127
Q

Irreversible production of ATP.

A

Phosphoenolpyruvate = Pyruvate + ATP

By Pyruvate kinase
Feedback inhibited by ATP and Alanine
Feedback activated by Fructose-1,6-BP

128
Q

Regulation by Fructose-2,6-BP
Activates PFK-1
Inhibits F-1,6-Bisphosphatase

A 
Fasting:
Increased Glucagon
Increased cAMP/Activated PKA
Increased Fructose-2,6-Bisphosphatase
Decreased Fructose-2,6-BP
Gluconeogenesis
Fed: 
Increased Insulin
Decreased cAMP/deactivated PKA
Increased PFK-2 activity
Increased Fructose-2,6-BP
Glycolysis
129
Q

Pyruvate dehydrogenase complex.

“TLC For Nancy”

A

PYRUVATE + NAD + COA = ACETYL-COA + CO2 + NADH

Requires:
Thiamine (B1)
Lipoic acid
CoA (B5)
FAD (B2)
NAD (B3)

Feedback inhibited by NADH, ATP, Acetyl-CoA
Feedback activated by NAD, ADP, Ca

130
Q

Vomiting
Rice water stools
Garlic breath

A

ARSENIC POISONING

Inhibits lipoic acid of pyruvate dehydrogenase complex.

131
Q

Pyruvate metabolism

A

Alanine transfers amino groups to liver (ALT)
Oxaloacetate (PC)
Acetyl-CoA for TCA (PDH)
Lactate (LDH) in RBC, WBC

132
Q

Order of TCA cycle.

“Citrate Is Krebs Starting Substrate For Making Oxaloacetate”

A 
Citrate
Isocitrate
a-Ketoglutarate
Succinyl-CoA
Succinate (requires GDP)
Fumarate (requires FAD)
Malate
Oxaloacetate

Citrate synthase combines Oxaloacetate and Acetyl-CoA to replenish Citrate

133
Q

First irreversible/rate limiting step of TCA.

A

ISOCITRATE + NAD = A-KETOGLUTARATE + NADH

By Isocitrate dehydrogenase

134
Q

Second irreversible step of TCA.

A

A-KETOGLUTARATE + NAD = SUCCINYL-COA + NADH

By a-KG dehydrogenase complex (same as PDH)

135
Q

Neurologic deficits
Lactic acidosis
Increased serum Alanine in infancy

A

PYRUVATE DEHYDROGENASE DEFICIENCY

Pyruvate shunted to Lactate and Alanine

Increased intake of exclusively ketogenic amino acids (Lysine, Leucine)

136
Q

Electron transport chain mechanism.

A

NADH (complex I) and FADH2 (complex II; succinate dehydrogenase) donate electrons to establish H gradient for ATP synthase (Complex V).

1 NADH = 2.5 ATP, 1 FADH2 = 1.5 ATP

Note - Lactate dehydrogenase responsible for NAD regeneration in anaerobic conditions

137
Q

Electron transport inhibitors.

A

RotenONE (complex I)
Antimycin A or An3mycin A (complex III)
CO/CN (“four letters,” complex IV)

138
Q

Uncoupling agents - loss of proton gradient but electron transport continues thereby generating heat instead.

A

2,4-Dinitrophenol (weight loss supplement)
Aspirin overdose
Thermogenin (brown fat)

139
Q 
Gluconeogenesis irreversible enzymes...
Pyruvate to Oxaloacetate (Biotin)
Oxaloacetate to Phosphoenolpyruvate (GTP)
F-1,6-BP to F-6-P
G-6-P to Glu

Note - Odd chained FAs produce Propionyl-CoA which enters TCA cycle as Succinyl-CoA to undergo gluconeogenesis

Note - Only occurs in liver as skeletal muscle lacks enzyme for G-6-P to Glu

A

Pyruvate Carboxylase (Mito)
Phosphoenolpyruvate Carboxykinase (Cytosol)
Fructose-1,6,-BPase (Cytosol)
Glucose-6-Pase (ER)

Note - Malate shuttle transfers Oxaloacetate out of mitochondria

140
Q

Glucose production from odd-chain fatty acids.

A

Propionyl-CoA enters TCA cycle as succinyl CoA and then undergo gluconeogenesis

Note - Propionyl-CoA carboxylase requires Biotin

141
Q

Oxidative (irreversible, rate-limiting) step of HMP shunt.

A

GLUCOSE-6-P = RIBULOSE-5-P + NADPH

By Glucose-6-P dehydrogenase
Feedback inhibited by NADPH

142
Q

Hemolytic anemia in the presence of fava beans, sulfonamides, primaquine, antituberculosis drugs, or infections.

On smear Heinz bodies (denatured hemoglobin) and Bite cells (from removal of Heinz bodies by spleen).

A

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY

X-linked recessive - Decreased NADPH leads to an inability to reduce glutathione (sensitive to oxidant stress)

Note - Most glycolytic enzyme deficiencies cause hemolytic anemia as RBCs can only use glucose for energy

143
Q 
Introduction of sugar with...
Failure to thrive
Hypoglycemia
Hypophosphatemia
Reducing substances in urine
A

FRUCTOSE INTOLERANCE

Autosomal recessive deficiency of Aldolase B causes…
Build up of Fructose-1-P
Depletion of inorganic phosphate
Inhibition of glycogenolysis and gluconeogenesis

Remove Fructose and Sucrose (Glucose + Fructose)

More mild form due to deficiency of Fructokinase (isolated reducing substances in urine) - Compensation by Hexokinase

144
Q 
Failure to thrive
Lethargy
Intellectual disability
Infantile cataracts
Hepatic dysfunction
Renal dysfunction (aminoaciduria, hyperchloremic metabolic acidosis)
Reducing substances in urine
E. coli sepsis in neonates
A

GALACTOSEMIA

Autosomal recessive deficiency of Galactose-1-P uridyltransferase (GALT) causes build up of Galactose-1-phosphate

Remove Galactose and Lactose (Glucose + Galactose) from diet (e.g. breastfeeding to soy formula feeding)

Note - More mild form (isolated late-onset cataracts) due to Galactokinase deficiency causing build up of Galactitol (osmotic agent)

145
Q

Mechanism of osmotic damage (cataracts, retinopathy, peripheral neuropathy) in hyperglycemia.

A

GLUCOSE = SORBITOL (BY ALDOSE REDUCTASE)

Schwann cells, retina, and kidneys lack Sorbitol Dehydrogenase to convert Sorbitol to Fructose for removal from cell.

146
Q

Bloating
Cramps
Flatulence
Osmotic diarrhea

Acidic stool
Increased breath hydrogen content

Biopsy shows loss of brush border if secondary (not congenital)

A

LACTASE DEFICIENCY

147
Q

Urea cycle intermediates - Used to dispose NH3 and form Fumarate for TCA

A

Mitochondrial:
CO2 + NH3 = Carbamoyl P (Carbamoyl Pase I)
Ornithine + Carbamoyl P = Citrulline

Cytosol:
Citrulline + Aspartate = Argininosuccinate = Fumarate + Arginine
Arginine = Urea + Ornithine

Note - First step decreased in patients with liver disease (hyperammonemia)

148
Q

Transport of ammonium between muscle and liver.

Note - Transamination requires B6

A

Amino acids + a-Ketoglutarate = Glutamate
Glutamate + Pyruvate = a-Ketoglutarate + Alanine

Alanine transferred to liver

Alanine + a-Ketoglutarate = Pyruvate + Glutamate
Pyruvate to Glucose for transport back to muscle

Note - a-Ketoglutarate levels depleted in hyperammonemia (e.g. hepatic encephalopathy)

149
Q

Cori cycle.

A

Lactate from muscle moved to liver and converted to Glucose (with ATP) for movement back to muscle.

150
Q 
Tremor (asterixis)
Slurred speech
Vomiting
Blurring vision
Somnolence
Cerebral edema
A

HYPERAMMONEMIA

Excess NH3 depletes a-Ketoglutarate, inhibiting TCA.

Limit dietary protein
Rifaximin to decrease colonic bacterial production
Lactulose to acidify GI tract and trap NH4+
Benzoate, Phenylacetate, Phenylbutyrate to bind NH4+
If urea cycle deficiency also consider Arginine

151
Q

Developmental delay
Intellectual disability
Poorly regulated respiration and body temperature
Poor feeding

A

N-ACETYLGLUTAMATE SYNTHASE DEFICIENCY
CARBAMOYL PHOSPHATE SYNTHETASE I DEFICIENCY

Both prevent conversion of NH3 to Carbamoyl Phosphate

152
Q

Clinical signs of hyperammonemia
Decreased BUN
Elevated orotic acid in blood and urine

A

ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY

X-linked recessive build up of Carbamoyl phosphate converted to Orotic acid (pyrimidine synthesis)

153
Q

Cause of albinism.

A

TYROSINASE DEFICIENCY

Deficient conversion of DOPA to Melanin.

154
Q 
Intellectual disability
Growth retardation
Seizures
Musty body odor
Hypopigmentation
A

PHENYLKETONURIA

Deficient Phenylalanine Hydroxylase - Tyrosine deficiency and buildup of Phenylketones in urine

Avoid Phenylalanine (Aspartame)
Tyrosine becomes essential

Note - Hypopigmented catecholaminergic areas (e.g. locus coeruleus)

Note - Similar presentation with Dihydrobiopterin Reductase deficiency which is required for both Phenylalanine Hydroxylase and Tyrosine Hydroxylase

155
Q 
Severe CNS defects
Intellectual disability
Irritability
Vomiting
Poor feeding
Urine smells like burnt sugar
A

MAPLE SYRUP URINE DISEASE

Deficient a-Ketoacid Dehydrogenase (B1) blocks degradation of branched amino acids (Isoleucine, Leucine, Valine) - Buildup of a-ketoacids in the blood.

Dietary limitation
Thiamine (B1) supplementation

156
Q

Bluish-black connective tissue and sclerae
Urine turns black on exposure to air
Debilitating arthralgia in adulthood

A

ALKAPTONURIA

Deficient Homogentisate Oxidase blocks degradation of Homogentisic acid (from Tyrosine) to Fumarate (for TCA)

157
Q 
Intellectual disability
Early thrombosis/atherosclerosis
Marfanoid body habitus
Lens subluxation (downward)
Osteoporosis
Kyphosis
A

HOMOCYSTINURIA

Cystathionine Synthase deficiency (increased Methionine) - Treat with Methionine restriction/B6

Methionine Synthase deficiency (increased Cysteine) - Treat with Methionine/B12

Note - Methionine is turned into SAM

158
Q

Recurrent precipitation of hexagonal cystine stones.

A

CYSTINURIA

Hereditary defect of renal PCT and intestinal amino acid transporters preventing reabsorption of Cystine, Ornithine, Lysine, and Arginine (“COLA”).

Confirm with urinary cyanide-nitroprusside test

Urinary alkalinization (K Citrate, Acetazolamide)
Chelating agents (Penicillamine)
159
Q

Derivative of Phenylalanine

A

Tyrosine = DOPA (=Melanin) = Dopamine = NE (requires Vit C) = Epi (requires SAM)

160
Q

Derivative of Tryptophan

A

Niacin

Serotonin = Melatonin

161
Q

Derivative of Glycine

A

Porphyrin = Heme

162
Q

Derivative of Glutamate

A

GABA

Glutathione

163
Q

Derivative of Arginine

A

Creatinine
Urea
Nitric Oxide

164
Q

Mechanism of Carbidopa

A

Inhibition of DOPA decarboxylase - required for conversion of DOPA to dopamine.

165
Q

Mechanism of Cortisol

A

Increased conversion of NE to Epi.

166
Q

Degradation of NE

A

Vanillylmandelic acid (with COMT)

167
Q

Degradation of Dopamine

A

Homovanillic acid

168
Q

Regulation of Glycogen Synthase

A

Insulin binds TKR which activates Protein Phosphatase

Inhibited by PKA

169
Q

Regulation of Glycogen Phosphorylase

A

Activated by Glycogen Phosphorylase Kinase
Inactivated by Protein Phosphatase

Note - Inhibited by ATP/G-6-P, Promoted by AMP (muscle)

170
Q

Activation of Glycogen Phosphorylase Kinase

A

Liver:
Epi/Glucagon activate Adenylate Cyclase
Increased cAMP activates PKA
Phosphorylation of Glycogen Phosphorylase Kinase

Muscle (no Glucagon receptors):
Muscle contraction increases Ca release from ER
Ca activates Glycogen Phosphorylase Kinase

171
Q

Glycogen stain (e.g. Whipple disease).

A

Periodic acid-Schiff

172
Q 
Severe fasting hypoglycemia
Hepatomegaly with steatosis
Lactic acidosis
Hyperlipidemia
Hyperuricemia
A

VON GIERKE DISEASE (TYPE I GLYCOGEN STORAGE DISEASE)

Deficiency in Glucose-6-Phosphatase
Deficient breakdown of G-6-P to Glucose
Liver and kidney involvement

Requires frequent oral glucose

173
Q

Normal glucose
General hypotonia
Cardiomegaly
Exercise intolerance

A

POMPE DISEASE (TYPE II GLYCOGEN STORAGE DISEASE)

Deficiency in lysosomal Acid Maltase (a-1,4-Glucosidase)

174
Q 
Ketotic hypoglycemia
Hepatomegaly without steatosis
Hypotonia and weakness
"limit dextrin" in cytosol
Normal lactate
A

CORI DISEASE (TYPE III GLYCOGEN STORAGE DISEASE)

Deficiency in Debranching Enzyme (a-1,6,-Glucosidase)
Liver and muscle involvement

175
Q 
Painful muscle cramps with normal lactate
Increased glycogen in muscle
Myoglobinuria with exercise
Normal blood glucose (liver)
Arrhythmia (electrolyte abnormalities)
"Second wind" phenomenon during exercise
A

MCARDLE DISEASE (TYPE V GLYCOGEN STORAGE DISEASE)

Deficiency in skeletal muscle Glycogen Phosphorylase (Myophosphorylase)

176
Q 
Episodic neuropathic pain
Angiokeratomas
Hypohidrosis
CKD
CAD
CVD
A

FABRY DISEASE

Lysosomal storage disease - Deficiency of a-Galactosidase A causes build up of Ceramide trihexoside

177
Q 
Lipid laden macrophages ("crumpled tissue paper")
Hepatosplenomegaly
Pancytopenia
Osteoporosis
Aseptic necrosis of femur
Bone crises
A

GAUCHER DISEASE

Lysosomal storage disease - Deficiency of Glucocerebrosidase causes build up of Glucocerebroside in lysosomes

178
Q 
Foam cells (lipid laden macrophages)
Hepatosplenomegaly
Hypotonia
Progressive neurodegeneration
Cherry red macula
A

NIEMANN-PICK

Lysosomal storage disease - Deficiency of Sphingomyelinase causes build up of Sphingomyelin

179
Q 
Onion skin lysosomes
No hepatosplenomegaly
Developmental delay
Progressive neurodegeneration
Cherry red macula
A

TAY-SACHS DISEASE

Lysosomal storage disease - Deficiency of Hexosaminidase A causes buildup of Ganglioside

180
Q

Globoid cells
Peripheral neuropathy
Developmental delay
Optic atrophy

A

KRABBE DISEASE

Lysosomal storage disease - Deficiency of Galactocerebrosidase causes build up of Galactocerebroside

181
Q

Central and peripheral demyelination
Ataxia
Dementia

A

METACHROMATIC LEUKODYSTROPHY

Lysosomal storage disease - Deficiency in Arylsulfatase A causes buildup of Sulfatides

182
Q 
Developmental delay
Dwarfism
Abnormal facies
Hepatosplenomegaly
Airway obstruction
Corneal clouding
A

HURLER SYNDROME

Sulfate accumulation due to Iduronidase deficiency

183
Q

Hurler syndrome with aggression and normal corneas.

A

HUNTER SYNDROME

X-linked recessive

184
Q

Fatty acid synthesis shuttle.

A

CITRATE SHUTTLE

Moves Citrate into cytoplasm
Forms Acetyl-CoA via ATP Citrate Lyase
Forms Malonyl-CoA via Acetyl-CoA carboxylase (+Biotin)

Note - Last step is rate-limiting and upregulated with Insulin

185
Q

Fatty acid degradation shuttle.

A

CARNITINE SHUTTLE

Moves Fatty Acyl-CoA into mitochondria
Forms Acetyl-CoA via b-oxidation (Ketones, TCA)

Note - Malonyl-CoA inhibits this shuttle to prevent b-oxidation of newly synthesized fatty acids

186
Q

Weakness
Hypotonia
Hypoketotic hypoglycemia

A

SYSTEMIC PRIMARY CARNITINE DEFICIENCY

Defect in transport of LCFA into mitochondria resulting in toxic accumulation.

187
Q 
Fasting child with...
Hypoketotic hypoglycemia
Liver dysfunction/Hyperammonemia
Vomiting
Lethargy
Seizures
Coma

Minor illness may lead to sudden death

A

MEDIUM CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY

Inability to break down Fatty Acids into Acetyl-CoA - Buildup of Fatty Acylcarnitines in blood.

Avoid fasting

Note - If KETOTIC hypoglycemia consider Propionyl CoA Carboxylase / Methylmalonyl CoA Mutase deficiencies (elevated urine Propionic acid) - Inability to break down protein into Succinyl-CoA

188
Q

Mechanism of ketoacidosis.

A

Alcohol dehydrogenase depletes NAD+ - Decreased conversion of Malate to Oxaloacetate / Lactate to Pyruvate

Oxaloacetate is required for conversion of acetyl-CoA to Citrate

Buildup of acetyl-CoA, shunting FFA and Glucose towards production of Ketones for use by skeletal muscle

Acetoacetate gives fruity odor to breath and is detected by urine test (b-hydroxybutyrate is not)

189
Q

Fed state energy supply.

A

Glycolysis and aerobic respiration.

Insulin promote storage of glycogen, fat, and protein.

190
Q

Fasting stage energy supply.

A

Hepatic glycogenolysis.

Glucagon and Epi stimulate use of glycogen reserves - Glucagon functions at the liver, while Epi functions at the Kidneys, Muscles, and Adipose tissues

191
Q

Starvation (1-3 d) energy supply.

A 
Hepatic glycogenolysis (depleted by day 1)
Hepatic gluconeogenesis from peripheral Lactate and Alanine

Adipose release of FFA
Muscle/liver shift use to FFA

Hepatic mobilization of Triglycerides (hormone sensitive lipase)
Converts FFA to Ketones via b-Oxidation
Converts Glycerol to Glucose via Glycerol Kinase (DHAP)

RBCs cannot use ketones (no mitochondria).

192
Q

Starvation (> 3 d) energy supply.

A

Adipose stores primary source of energy
Brain begins using ketones
Eventually protein degradation results in organ failure

193
Q

Rate limiting step of cholesterol synthesis.

A

HMG COA = MEVALONATE

By HMG CoA reductase

Feedback inhibited by Glucagon and Cholesterol
Feedback activated by Insulin and Thyroxine

Note - HMG-CoA Synthase converts Acetoacetyl-CoA to HMG-CoA, which can also form Ketones via HMG-CoA Lyase

194
Q

Function of chylomicrons.

A

Dietary TGs to peripheral tissues via LPL (Insulin)
Cholesterol remnants to liver

Contains Apo-B48, Apo-CII, Apo-E

195
Q

Function of VLDL.

A

Hepatic TGs to peripheral tissues.

Contains Apo-B100, Apo-CII, Apo-E

Note - Converted to IDL by LPL to deliver remaining TGs back to liver

196
Q

Function of LDL.

A

Hepatic cholesterol to peripheral tissues

Contains Apo-B100 for binding to LDLR

Note - Formed from IDL by Hepatic Lipase (HL)

197
Q

Function of HDL.

A

Peripheral cholesterol to liver

Contains Apo-A1 (required for LCAT)
Suppository for Apo-CII (required for LPL function)
Suppository for ApoE (required for liver reuptake)

Secreted by both liver and intestines
Increased synthesis with EtOH

198
Q

Function and regulation of hormone sensitive lipase

A

Degradation of TGs stored in adipocytes during fasting

Induced by Catecholamines, Glucagon, ACTH
Inhibited by Insulin

199
Q

Function of LCAT (lecithin-cholesterol acyltransferase).

A

In the presence of ApoA, catalyzes esterification of HDL.

Transferred to VLDL/IDL/LDL by CETP (cholesterol ester transfer protein).

200
Q 
Pancreatitis
Hepatosplenomegaly
Eruptive/pruritic xanthomas
Lipemia retinalis
No increased risk of atherosclerosis

Creamy layer in supernatant
Elevated Cholesterol
Elevated Chylomicrons
Elevated TG

A

FAMILIAL HYPERCHYLOMICRONEMIA

Autosomal recessive LPL or ApoC-II deficiency

201
Q 
Premature atherosclerosis (may have MI < 20 y/o)
Tendon (achilles) xanthomas
Xanthelasmas
Elevated Cholesterol (300-700)
Elevated LDL
A

FAMILIAL HYPERCHOLESTEROLEMIA

Autosomal dominant LDLR or Apo-B100 deficiency

202
Q

Coronary artery disease
Acute pancreatitis

Elevated VLDL
Normal LDL
Elevated TG (> 1000)

A

FAMILIAL HYPERTRIGLYCERIDEMIA

Autosomal dominant LPL deficiency

203
Q

Mechanism of hyperhomocysteinemia.

Note - Independent risk factor for thrombotic events

A

Deficient methyl-THF reductase enzyme
Decreased conversion of THF to methyl-THF
Uncouples Folate and Methionine cycles

Normally with Methionine Synthase (B12)…
Methyl-THF + Homocysteine = THF + Methionine

Note - Cells require THF form of folate

204
Q

Mechanism of E. coli lactose metabolism

A

LacI constitutively produces repressor protein

Lactose leads to conformational change in repressor protein

Repressor is released from operator region (minimal transcription)

Decreased glucose removes inhibition of adenylate cyclase

Increased cAMP activates cAMP-CAP which binds upstream to promoter region (maximal transcription)

Increased transcription of Lac Z (b-galactosidase), Y (permease), and P (binding site for RNA polymerase)

205
Q

Premature atherosclerosis
Palmar xanthomas

Elevated Chylomicrons
Elevated VLDL remnants

A

FAMILIAL DYSBETALIPOPROTEINEMIA

Autosomal recessive ApoE mutation

206
Q

Reactions limited to…
Cytosol
Mitochondria
Both

A

Cytosol: Glycolysis, HMP shunt, Fatty acid synthesis

Mitochondrial: TCA, Acetyl-CoA production, Oxidative phosphorylation, b-Oxidation, Ketogenesis

Both: Urea, Heme, Gluconeogenesis

207
Q 
Failure to thrive
Developmental delay
Megaloblastic anemia refractory to B12/Folate
Orotic acid in urine
No hyperammonemia
A

OROTIC ACIDURIA

Autosomal recessive mutation in UMP synthase - inability to convert orotic acid to UMP in pyrimidine synthesis

Treat with Uridine monophosphate (bypass enzyme)

208
Q

Fastest metabolized sugar

A

FRUCTOSE

F-1-P is converted by Aldolase B to DHAP/Glyceraldehyde which can enter as Glyceraldehyde-3-P (to Pyruvate)

Note - This bypasses the major rate limiting step of Glycolysis

209
Q

Effect of Glucagon on pancreas

A

Increases Insulin secretion for glucose utilization

Note - Insulin decreases Glucagon release

210
Q

Axonal transport direction of…
Dynein
Kinesin

A

Retrograde

Anterograde

211
Q

Probability of 2 allele from separate foci appearing together

A

Occurrence rate (allele 1) x Occurrence rate (allele 2)

If observed frequency is greater than predicted there is linkage disequilibrium due to close proximity

212
Q

Initiation of transcription

A

RNA Pol II binding to CAAT/TATA in promoter
Activator binding Enhancing region (location varies)
Interaction of Activator with RNA Pol II

Note - RNA Pol I makes rRNA, and RNA Pol III makes tRNA

213
Q

Codes for border of a splice site

A

5’-GU…AG-3’

214
Q

Genetic mutation found in multiple offspring but not in either parent

A

GERMLINE MOSAICISM

Unlike somatic mosaicism is inherited by offspring

215
Q

Progressive spastic diplegia
Growth delay
Abnormal movements

Note - Normal BUN

A

ARGINASE DEFICIENCY

Elevated Arginine

216
Q

Calories per gram from…
Protein
Carbohydrates
Fat

A

4
4
9

217
Q

Enzymes required in Purine synthesis…
Orotic acid + PRPP = UMP
UDP = dUDP + CTP
dUMP + THF = dTMP

A

Dihydroorotate dehydrogenase
Ribonucleotide reductase
Thymidylate synthase

218
Q

Enzyme required for Pyrimidine synthesis…

PRPP = IMP = AMP + GMP

A

Inosine Monophosphate Dehydrogenase

219
Q

Gene mutation responsible for…
Orthostatic hypotension
Impaired tear formation
Reduced sensitivity to pain

A

FAMILIAL DYSAUTONOMIA

IKAP loss of function

220
Q

Eukaryotic translation

A

initiated when the small ribosomal subunit binds the 5’ cap of mRNA and scans for the methionine start codone

eIF (euk. initiation factors) facilitate this

221
Q

How does eukaryotic translation differ during apoptosis

A

activation of eIF degradation leads to interruption of translation

as a result alternative method of internal ribosome entry is used. Distinct nucleotide sequence called the internal ribosome entry site (IRES) attracts the eukaryotic ribosome to mRNA and allows translation to begin in the middle of the mRNA sequence

222
Q

initiation seq in euk translation

initiation seq in prok translation

A

kozak consensus sequence

shine Dalgarno sequence

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