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Flashcards in Biochemistry Deck (293):
1

What gives DNA its (-) charge?

Phosphate groups

2

What gives histones their (+) charge?

Lysine and Arginine (what the octamer subunits primarily consist of)

3

What histones make up the nucleosome core in the "bead" on a string of chromatin? What histone ties the nucleosome "beads" together in a string?

Nucleosome core histones: H2A, H2B, H3, H4

H1 is the only histone that's not in the nucleosome core; it ties the nucleosome core/beads together in a "string"

*referring to chromatin here (chromatin is the condensed form of DNA that allows it to fit into the nucleus)

4

Heterochromatin vs Euchromatin

Heterochromatin: highly condensed, transcriptionally inactive, sterically inaccessible

Euchromatin: less condensed, transcriptionally active, sterically accessible

5

How to mismatch repair enzymes distinguish between old and new strands?

Because template strand cytosine and adenine are methylated in DNA replication; this allows mismatch repair enzymes distinguish between old and new strands

6

What does hypermethylation do to DNA transcription?

inactivates transcription of DNA ("methylation makes DNA mute")

7

What does histone acetylation do?

Relaxes DNA coiling, allowing for transcripiton ("acetylation makes DNA active")

8

List the Purines. How many rings?

PURe As Gold: Adenine and Guanine
Have 2 rings

9

List the Pyrimidines. How many rings?

CUT the PY: Cytosine, Uracil, Thymine
Have 1 ring

10

RNA vs DNA nucleotides?

Uracil in RNA
Thymine in DNA

11

Which nucleotide has a ketone?
Which has a methyl?
Which makes uracil when deaminated?

Guanine has a ketone
Thymine has a methyl
Deamination of cytosine makes uracil

12

G-C vs A-T bonds:

G-C --> have 3 H-bonds, stronger than A-T bonds, which have 2 H-bonds

the more G-C content, the higher the melting point

13

Nucleoside vs Nucleotide

Nucleoside = base + ribose (sugar)
Nucleotide = base + ribose + phosphate; linked by 3'-5' phosphodiester bond

14

Which amino acids are necessary for purine synthesis?

Glycine
Aspartate
Glutamine

15

Ribonucleotide Reductase

Convert ribonucleotides to deoxyribonucleotides in de novo pyrimidine synthesis (UDP --> dUDP)

16

Purine synthesis

1) Start with sugar + phosphate (PRPP)
2) Add base

17

Pyrimidine synthesis

1) Make temporary base (orotic acid)
2) Add sugar + phosphate (PRPP)
3) Modify base

18

Rate limiting enzyme in Purine synthesis?

Glutamine-PRPP-Amidotransferase (catalyzes step from PRPP --> --> --> IMP)

19

Rate limiting enzyme in Pyrimidine synthesis?

CPS - 2 = carbamoyl phosphate synthetase 2 (catalyzes step from ATP + CO2 + Glutamine --> Carbamoyl Phosphate)

20

Hydroxyurea mechanism

anti-cancer drug; inhibits ribonucleotide reductase (UDP-->dUDP)

21

6-mercaptopurine mechanism

blocks de-novo purine synthesis by blocking PRPP synthetase (Ribose-5-P --> PRPP)

22

5-Fluorouracil mechanism

Inhibits thymidylate synthase (dUMP --> dTMP)
(get decreased dTMP)

23

Methotrexate mechanism

inhibits dihydrofolate reductase (DHF-->THF); [thymidylate synthase uses THF (tetrahydrofolate), the active form of folic acid, to convert dUMP-->dTMP]
(get decreased dTMP)

24

Trimethoprim mechanism

inhibits bacterial dihydrofolate reductase (get decreased dTMP)

25

Mycophenylate mechanism

inhibits IMP (inosine monophosphate) dehydrogenase (IMP-->GMP)

26

How would a folic acid deficiency affect pyrimidine synthesis?

Thymidylate synthase (converts dUMP --> dTMP) uses THF, which is the active form of folic acid. So, without it, get decreased dTMP.

27

increased orotic acid in urine, megaloblastic anemia (that does not improve with vitamin B12 or folic acid), FTT; no hyperammonemia

Orotic aciduria (inability to convert orotic acid to UMP in the de novo pyrimidine synthesis pathway; d/t defect in either orotic acid phosphoribosyltransferase or orotidine-5'-phosphate decarboxylase)
-Autosomal recessive
-treat with oral uridine administration

28

What is the cause of orotic aciduria?

can't convert orotic acid to UMP in the de novo pyrimidine synthesis pathway; due to a defect in either orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase
-Autosomal recessive

29

Adenosine Deaminase Deficinecy

Results in SCID (severe combined immunodeficiency disease)
can't convert adenosine-->inosine in the purine salvage pathway, so get excess ATP and dATP, and thus feedback inhibition of ribonucleotide reductase (which imbalances the nucleotide pool); so prevents DNA synthesis and thus decreases the lymphocyte count

30

Absence of HGPRT

Lesch-Nyhan syndrome
-HGPRT converts hypoxanthine to IMP and guanine to GMP; without it, have defective purine salvage. Get excess uric acid production and de novo purine synthesis (so increased PRPP amidotransferase activity)
-X-linked recessive
-Findings: retardation, self-mutilation (lip-biting), aggression, hyperuricemia, gout, choreoathetosis
-Trtmnt: allopurinol (can't treat CNS symptoms)

31

Allopurinol mechanism

inhibits xanthine oxidase (converts xanthine --> uric acid)

32

Origin of Replication

sequence of genome where DNA replication begins; single in prokaryotes, multiple in eukaryotes

33

Helicase

unwinds DNA template at replication fork

34

SSBPs (single-stranded binding proteins)

prevent strands from reannealing (stabilize unwound DNA)

35

Fluoroquinolones mechanism?

inhibit DNA gyrase (prokaryotic topoisomerase II)

36

Etoposide mechanism?

Inhibits human tropoisomerase (anti-cancer drug)

37

DNA topoisomerases

create a nick in the helix to relieve supercoils created during replication

38

DNA polymerase III

-Prokaryotic only
-Elongates leading strand by adding deoxynucleotides to the 3' end.
-Elongates lagging strand until it reaches the primer of the preceding fragment
-3'-->5' exonuclease activity "proofreads" each added nucleotide.
*SO: 5'-->3' synthesis; 3'-->5' proofreading exonuclease

39

DNA polymerase I

Prokaryotic only
-Degrades RNA primer and fills in the gap with DNA (excision repair)
*SO:excises RNA primer with 5'-->3' exonuclease

40

Telomerase

adds DNA to 3' ends of chromosomes to avoid loss of genetic material with each duplication

41

anti-topoisomerase antibody

anti-SCL70 - in diffuse scleroderma

42

Nucleotide Excision Repair

-repair for small areas of damage
-mutated in xeroderma pigmentosum (can't repair thymine dimers after UV light exposure)
-thymine dimers from UV light are usually repaired by NER

43

Base Excision Repair

-repair 1 damaged base

44

Mismatch Repair

unmethylated, newly synthesized string is recognized, mismatched nucleotides removed, and gap is filled and reasealed
-mutated in HNPCC (hereditary nonpolyposis colorectal cancer)

45

Nonhomologous end joining (type of double strand repair)

-mutated in ataxia telangiectasia
-brings together 2 ends of DNA fragments

46

-most abundant type of RNA?
-longest type?
-smallest type?

"rampant, massive, tiny"
rRNA = most abundant
mRNA = longest
tRNA = smallest

47

mRNA stop codons

-UGA (u go away)
-UAA (u are away)
-UAG (u are gone)

48

Promoter

site where RNA polymerase and other transciption factors bind to DNA
-located 25 (TATA or Hogness box) or 70 (CAAT box) bases upstream from their genes

49

Enhancers and Silencers

Enhancers = stretch of DNA that binds transcription factors
Silencers = where negative regulators (repressors) bind
*Both can be located anywhere upstream, downstream, or even within transcribed gene

50

Eukaryotic RNA Polymerases I, II, III

RNA pol I: makes rRNA
RNA pol II: makes mRNA
RNA pol III: makes tRNA

51

Prokaryotic RNA polymerase

only 1 RNA polymerase --> makes all 3 kinds of RNA

52

Rifampin inhibits?

inhibits prokaryotic RNA polymerase

53

Where are rRNA, mRNA, tRNA synthesized?

rRNA --> synthesized in nucleolus
mRNA and tRNA --> synthesized in nucleoplasm

54

After transcription, processing of the pre-mRNA in the nucleus:

1) Capping on 5'-end
2) Polyadenylation on 3' end (poly-A tail)
3) splicing out of introns by the spliceosome (so, introns stay in nucleus, exons leave nucleus, form mRNA)

55

antibodies to spliceosomal snRNPs?

Lupus pts

56

Effect of glucose on the lac operon?

in presence of glucose: glucose inhibits cAMP, so get decreased cAMP --> decreased CAP (activator protei) --> inhibition of lac operon
So:
-if have glucose --> lac operon is off
-if not lactose --> lac operon is off
-if no glucose, but have lactose --> lac operon is ON!

57

Aminoacyl-tRNA synthetase: what does it do and where does it act?

works at the 3'-OH-end of the tRNA; charges the amino acid onto the tRNA molecule
-uses ATP

58

Tetracyclines mechanism

Tetracyclines bind 30S subunit, preventing attachment of aminoacyl-tRNA

59

Steps of Elongation in protein synthesis:

1) aminoacyl-tRNA binds A site
2) ribosomal rRNA ("ribozyme" = peptidyl transferase) catalyzes peptide bond formation; transfers growing polypeptide to amino acid in A site
3) Ribosome advance 3 nucleotides toward 3' end of RNA, moving peptidyl RNA to P site (translocation)

APE:
A site: incoming Aminoacyl-tRNA
P site: accommodates growing Peptide
E site: holds Empty tRNA as it Exits

60

Aminoglycosides mechansim:

bind 30S on prokaryotic ribosome, and inhibit formation of the initiation complex and cause misreading of mRNA

61

Chloramphenicol mechanism

inhibits 50S peptidyltransferase

62

Macrolides mechanism

act on 50S subunit and block translocation (step 3 of elongation factor)

63

Clindamycin and Chloramphenicol mechanism

act at 50S; block peptide bond formation

64

Regulation of cell cycle by:
-Cyclic-dependent kinases
-Cyclins
-Cylcin-CDK complexes
-Rb and p53 (tumor suppressors)

*CDKs = cyclin-dependent kinases: constitutive and inactive; expressed constantly, but inactive unless activated
*Cyclins = activate CDKs
*Cyclin-CDK complexes: must be both activated and inactivated for cell cycle to progress
*Rb and p53: inhibit G1-->S progression; p53 also inhibits G2-->Mitosis

65

Which cell types are "permanent", remaining in G0, regenerating from stem cells?

neurons, skeletal and cardiac muscles, RBCs

66

Which cell types are stable/quiescent --> enter G1 from G0 when stimulated?

hepatocytes, lymphocytes

67

Which cell types are labile --> never go to G0, divide rapidly with a short G1?

bone marrow, gut epithelium, skin, hair follicles (this type are most susceptible to cancer drugs)

68

Nissl bodies

RER in neurons (in dendrites; not in axons) --> synthesize enzymes and peptide neurotransmitters

69

What types of cells are rich in RER?

mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells

70

What types of cells are rich in SER?

liver hepatocytes (for drug and poison detox) and steroid-hormone producing cells of the adrenal cortex

71

Which amino acids are modified by the golgi?

-Asparagine
-Serine
-Threonine

72

Failure to add mannose-6-phosphate to lysosome proteins results in what disease?

I-cell disease = Inclusion cell disease;
inherited lysosomal storage disease. Since not tagged by mannose-6-phosphate, enzymes are secreted outside the cell instead of to the lysosome.
-Features: coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes; often fatal in childhood

73

Peroxisome function

catabolism (breakdown) of very long fatty acids and amino acids

74

Proteasome function

barrel-shaped; degrades damaged or unnecessary proteins tagged for destruction with ubiquitin

75

Dynein and Kinesin

microtubule proteins:
-dynein: retrogradeto microtubule (+ to -)
-kinesin: anterograde to microtubule (- to +)

76

Immune disease due to a defect in microtubule polymerization?

Chediak-Higashi syndrome: microtubule polymerization defect resulting in decreased fusion of phagolysosomes and lysosomes; get recurrent pyogenic infections, partial albinism, peripheral nueropathy

77

Drugs that act on microtubules

1)-Bendazoles (anti-helminthic)
2) Griseofulvin (anti-fungal)
3) Vincristine/Vinblastine (anti-cancer) - block polymerization of microtubules
4) Paclitaxel (anti-breast cancer) - stabilizes microtubules
5) Colchicine (anti-gout)

78

Kartagener's syndrome: cause, presentation

*immotile cilia due to a dynein arm defect
*Presentation:
-infertility (male and female)
-bronchiectasis
-recurrent sinusitis (because can't push bacteria/particles out)
-situs inversus

79

Cytoskeletal elements

-actin and myosin
-microtubule (for movement)
-intermediate filaments (for structure: vimentin, desmin, cytokeratin, lamins, GFAP, neurofilaments)

80

Contents of the plasma membrane

-50% cholesterol
-50% phospholipids (phosphatidylcholine, lecithin, phosphatidyl inositol)
-also: sphingolipids, glycolipids, proteins

81

Stains for intermediate filaments: What types of cells do these stains stain?
-Vimentin
-Desmin
-Cytokeratin
-GFAP (glial fibrilary acid proteins)
-Neurofilaments

-Vimentin-->Connective tissue (so use for sarcomas, some carcinomas)
-Desmin --> muscle (rhabdomyosarcoma, leiomyosarcoma)
-cytokeratin--> epithelial cells (carcinomas, some sarcomas)
-GFAP --> neuroglia
-Neurofilaments --> neurons (adrenal neuroblastoma,primitive neuroectoderm tumors)

82

Oubain mechanism

inhibits the Na/K-ATPase by binding to the K site

83

Cardiac glycosides (digoxin, digotoxin) mechanism:

inhibit Na/K-ATPase, leading to indirect inhibition of Na/Ca-exchange; resulting in increased intracellular Ca and thus increased cardiac contractility

84

What are the 4 types of collagen?

"Strong, Slippery, Bloody BM!"
Type I: (90%) = Strong --> bone, skin, tendon, dentin, fascia, cornea, late wound repair
Type II: Slippery --> Cartilage (including hyaline)
Type III: Bloody --> skin, blood vessels, uterus, fetal tissue, granulation tissue (early wound healing)
Type IV: BM --> basement membrane and basal lamina

85

Collagen synthesis steps:

--Within Fibroblasts--

1) Synthesis in RER: Preprocollagen: Gly-X-Y polypeptide (X and Y are proline or lysine)
2) Hydorxylation of proline and lysine in ER: requires Vitamin C
3) Glycosylation in ER: formation of procollagen
4) Exocytosis of procollagen into extracellular space

--outside fibroblasts--

5) Proteolytic processing: procollagen is cleaved to become tropocollagen
6) Cross-linking: Collagen fibrils are formed by cross-linking tropocollagen molecules

86

Osteogenesis imperfecta:
-what type of collagen is defective?

="brittle bone disease"
-Autosomal dominant, abnormal type 1 collagen (type 2 is fatal in-utero)
-defect is in the glycosylation phase (step 3) of collagen synthesis; can't form triple helix (procollagen) from the pro-alpha-chain

-Symptoms:
-multiple fractures (may be during birth; may look like child abuse)
-blue sclerae
-hearing loss
-dental problems due to lack of dentin

87

Blue Sclerae?

Osteogenesis imperfecta

88

Defect in Type III collagen?

Ehlers-Danlos syndrome (defect is ouside fibroblasts, can't crosslink tropocollagen to make collagen fibrils)
*"bloody" collagen defect (can be other types, but type III is most common)
-hyperextensible skin
-tendency to bleed (easy brusing, berry aneurysms, organ rupture)
-hypermobile joints (joint dislocation)

89

Type IV collagen defect

Alport syndrome --> "can't see, can't pee, can't hear"
-usually X-linked recessive
-progressive hereditary nephritis and deafness; may have ocular disturbances too.

90

Which two amino acids is elastin rich in?

glycine and proline

91

alpha-1-antitrypsin, elastase, elastin... relationship?
What if alpha-1-antitrypsin is deficient?

Elastin is broken down by elastase.
alpha-1-antitrypsin inhibits elastase, so inhibits elastin breakdown.
in alpha-1-antitrypsin deficiency: can't inhibit elastase, so get excessive elastase activity and excessive elastin breakdown (can result in panacinal emphysema)

92

Blotting procedures: Southern, Northern, Western, Southwestern

"SNoW DRoP"
Southern Blot --> DNA sample; DNA probe
Northern Blot --> RNA sample; DNA probe
Western Blot --> Protein sample; antibody probe
Southwestern Blot --> identifies DNA-binding proteins, like transcription factors,using labeled oligonucleotide probes

93

sensitivity and specificity of ELISA (enzyme-linked immunosorbent assay)? how does it work/what does it test?

ELISA tests antigen-antibody reactivity; probe pt's blood sample with either:
-test antigen --> to see if immune system recognizes it/if antibody is there
-test antibody --> to see if a certain antigen is there

*solution has a color reaction if positive
*sensitivity and specificity both close to 100%

*Ex of how it works:
1) put antigen to a virus in tube
2) add pt's serum (so, if pt has antibodies to virus, antibodies will bind virus antigens); rinse tube to get rid of unbound antibodies
3) add anti-human Ig that is also connected to an enzyme; these anti-human antibodies will bind the antibody-antigen complexes
4) add a substrate that will cause a color change of the enzyme, it it's bound
***Voila!***

94

Variable expression

severity of phenotype varies from 1 person to another (ie neurofibromatosis type 1, tuberous sclerosis --> may have varying severity)

95

Incomplete penetrance

not all individuals with mutant genotype show mutant phenotype

96

Pleiotropy

1 gene has >1 effect on an individual's phenotype (ie PKU--> lots of seemingly unrelated symptoms)

97

Imprinting

differences in phenotype depend on whether mutation is maternal or paternal origin; occurs due to DNA methylation (ie Prader-Willi and Angelman's syndromes)

98

Loss of heterozygosity

if a patient inherits or develops a mutation in a tumor suppressor gene, the complementary all has to be deleted/mutated before cancer develops (Retinoblastoma)

99

Dominant Negative mutation

a heterozygote produces a non-functional altered protein that also prevents the normal gene product from functioning; exerts a dominant effect (ie nonfunctional factor may bind DNA, thus preventing functional factor from binding)

100

Linkage disequilibrium

tendency for certain alleles at 2 linked loci to occur together more often than expected by chance; measured in a popl

101

Lyonization

random X-inactivation in females

102

Mosaicism

cells in body differ in genetic makeup d/t postfertilization loss of genetic info during mitosis
*germ-line/gonadal mosaic - child has a disease not carried by parent's somatic cells

103

Locus heterogeneity

mutations at different loci can produce same phenotype

104

heteroplasmy

presence of both normal and mutated mitochondrial DNA --> so, have variable expression in mitochondrial inherited disease

105

uniparental disomy

kid gets 2 copies of a chromosome from 1 parent, none from the other

106

Hardy-Weinberg equations and what does the law assume?

p^2 + 2pq + q^2 = 1
p + q = 1
p^2 = freq of homozygosity for p
q^2 = freq of homozygosity for q
2pq = freq of heterozygosity (carrier freq)

if X-linked:
-males = q
-females = q^2

Law assumes:
-no mutation
-no selection
-random matig
-no migration

107

Prader-Willi vs Angelman's syndrome

both due to inactivation or deletion of genes on chromosome 15
-due to imprinting (1 allele is inactive d/t methylation); may also be d/t uniparental disomy
P-W: maternal allele is inactivated; paternal allele should be active but's deleted; mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

Angelman's: inactive paternal allele; maternal allele should be active but is deleted; "happy puppet" --> MR, seizures, ataxia, inappropriate laughter.

108

Mitochondrial myopathies

seen in all offspring of infected mother
-leber's hereditary optic neuropathy (acute loss of central vision)
-myoclonic epilepsy
-mitochondrial encephalopathy
-"ragged red fibers" on micrsocopy

109

Locus heterogeneity

mutations at different loci can produce same phenotype

110

heteroplasmy

presence of both normal and mutated mitochondrial DNA --> so, have variable expression in mitochondrial inherited disease

111

uniparental disomy

kid gets 2 copies of a chromosome from 1 parent, none from the other

112

Hardy-Weinberg equations and what does the law assume?

p^2 + 2pq + q^2 = 1
p + q = 1
p^2 = freq of homozygosity for p
q^2 = freq of homozygosity for q
2pq = freq of heterozygosity (carrier freq)

if X-linked:
-males = q
-females = q^2

Law assumes:
-no mutation
-no selection
-random matig
-no migration

113

Prader-Willi vs Angelman's syndrome

both due to inactivation or deletion of genes on chromosome 15
-due to imprinting (1 allele is inactive d/t methylation); may also be d/t uniparental disomy
P-W: maternal allele is inactivated; paternal allele should be active but's deleted; mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

Angelman's: inactive paternal allele; maternal allele should be active but is deleted; "happy puppet" --> MR, seizures, ataxia, inappropriate laughter.

114

Mitochondrial myopathies

seen in all offspring of infected mother
-leber's hereditary optic neuropathy (acute loss of central vision)
-myoclonic epilepsy
-mitochondrial encephalopathy
-"ragged red fibers" on micrsocopy

115

cell signaling defect of fibroblast growth factor (FGF) Receptor 3

Achondroplasia
-dwarfism, short limbs (but normal head and trunk)
-assoc with advanced paternal age
-autosomal dominant

116

90% of cases are due to mutation in PKD1 (on chrom 16)

ADPKD (autosomal dominant polycystic kidney disease)
-autosomal dominant
-ALWAYS BILATERAL, massive enlargement of kidneys d/t multiple cysts
-flank pain, hematuria, hypertension, progressive renal failure
-assoc with polycystic liver disease, berry aneurysms, mitral valve prolapse

117

Mutations of APC gene on chromosome 5

Familial Adenomatous Polyposis
-autosomal dominant
-colon covered with adenomatous polyps after puberty
-progresses to colon cancer, so have to do colonectomy

118

Elevated LDL d/t defective/absent LDL receptor, tendon xanthomas, atherosclerosis and MI early in life

Familial hypercholesterolemia (hyperlipidemia type IIA)
-autosomal dominant
-heterozygotes: cholesterol approx 300 mg/dL
-homozygotes: cholesterol approx 700 + mg/dL; may develop MI before age 20

119

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)

-autosomal dominant, inherited disorder of blood vessels
-telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations

120

spectrin or ankyrin defect

Hereditary spherocytosis
-autosomal dominant
-spheroid RBCs, d/t spectrin or ankyrin defect (responsible for RBC structure)
-hemolytic anemia
-increased MCHC (mean cell hemoglobin concentration)
-dx by osmotic fragility test
-splenectomy = curative

121

CAG trinucleotide repeats; gene on chromosome 4

Huntington's disease
-autosomal dominant
-depression, dementia, choreiform mvmnts, caudate atrophy, decreased GABA and decreased ACh
-symptoms between 20-50 yo

122

Fibrillin gene mutation

Marfan's syndrome
-autosomal dominant
-connective tissue disorder affecting skeleton, heart, eyes
-tall, long extremities, pectus excavatum, hyperextensive joints, arachnodactyly
-cystic medial necrosis of aorta --> aortic incompetence, dissecting aorta, berry aneurysms; floppy mitral valve
-subluxation of lenses

123

inheritance pattern of the MEN syndromes (multiple endocrine neoplasias)

autosomal dominant
-MEN 2A and 2B are associated with ret gene

124

cafe au lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas), skeletal disorders (ie scoliosis), optic pathway gliomas

Neurofibromatosis type 1 = von Recklinghausen's disease
-autosomal dominant
-on chrom 17

125

Bilateral acoustic schwannomas, juvenile cataracts
-what disorder is this?
-what's its mode of inheritance?
-what gene is mutated and on what chromosome?

Neurofibromatosis type 2
-autosomal dominant
-NF2 gene on chromosome 22

126

Tuberous Sclerosis
-mode of inheritance?
-Findings?

-autosomal dominant
-incomplete penetrance and variable presentation
-Findings: facial lesions (adenoma sebaceum), hypopigmented ash-leaf spots, coritcal and retinal hamartomas, seizures, MR, renal cysts, renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas

127

ash leaf spots (hypopigmented lesions on skin) + cardiac rhabdomyomas (+other possible symptoms too...)

Tuberous sclerosis

128

Deletion of VHL gene on chromosome 3

von Hippel-Lindau disease
-autosomal dominant
-deletion of VHL gene = tumor suppressor gene; get constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors
-hemangioblastomas of retina/cerebellum, medulla
-50% of pts develop multiple bilateral renal cell carcinomas and other cancers

129

List the X-linked recessive disorders

"Be Wise, Fool's GOLD Heeds Silly Hope"
-Bruton's agammaglobulinemia
-Wiskott-Aldrich syndrome
-Fabry's disease
-G6PD deficiency
-Ocular albinism (general albinism = aut recessive!)
-Lesch-Nyhan syndrome
-Duchenne's (and Becker's) muscular dystrophy
-Hunter's Syndrome
-Hemophilia A and B
...also, Fragile X....

130

meconium ileus in a newborn. think:

-Cystic fibrosis
-Hirschsprung's disease

131

CFTR gene mutation; mode of inheritance? Function of gene normally?

Cystic Fibrosis
-autosomal recessive
-CFTR gene codes for transmembrane protein that puts Cl from cell into lumen of pancreatic ducts and into lumen of airways; Na follows Cl into lumen, and water follows Na. But, with CFTR defect (abnormal protein folding), decreased water into lumen --> thick mucus

-mucus plugs lungs, pancreas, liver..

132

most common lethal genetic disease of Caucasians?

cystic fibrosis

133

recurrent pulmonary infections + malabsorption + caucasian child? Think:

cystic fibrosis

134

Why are males with CF infertile?

bilateral absence of vas deferens

135

Treatment for CF pts?

-N-acetylcysteine (inhaled; loosens mucus plugs)
-antibiotics (even fluoroquinolone in kids)
-fat soluble vitamins: A, D, E, K
-pancreatic enzymes

136

Longest known human gene?

Dystrophin gene (DMD) --> mutated in Duchenne's and Becker's muscular dystrophy

137

Defect affecting the methylation and expression of the FMR1 gene and trinucleotide repeat of CGG?

Fragile-X syndrome
-X-linked defect
-2nd most common cause of genetic MR
-MR, enlarged testes, long face, large jaw, large everted ears, autism, mitral valve prolapse

138

What are the 4 trinucleotide repeat expansion diseases (and what's being repeated)?

"Tri Hunting for my Fried Eggs (X)"
1) Huntington's disease (CAG)
2) Myotonic dystrophy (CTG)
3) Friedrich's ataxia (GAA)
4) Fragile X (CGG)
--> all may show anticipation!

139

flat facies, epicanthal folds, excessive skin at nape of neck, gap between 1st 2 toes, duodenal atresia, congenital heart disease

Down's syndrome

140

What does may a 1st trimester ultasound of a fetus with trisomy 21 show?

increased nuchal translucency

141

decreased alpha-fetoprotein
increased beta-hCG
decreased estriol
increased inhibin A

Down's syndrome

142

decreased alpha-fetoprotein
decreased beta-hCG
decreased estriol
normal inhibin A

Edward's syndrome (trisomy 18)

143

MR, rocker-bottom feet, small jaw, low-set ears, clenched hands, congenital heart disease

Edward's syndrome (trisomy 18)

144

Pregnancy quad screen results in Patau's syndrome (trisomy 13)

Normal alpha-fetoprotein, beta-hCG, estriol, inhibin A

145

MR, rocker-bottom feet, small eyes, cleft lip/palate, holoprosencephaly (single mid-line eye), polydactyly, congenital heart disease

Patau's syndrome (trisomy 13)

146

Which chromosomes are commonly involved in Robertsonian translocations?

13, 14, 15, 21, 22

147

MR, microcephaly, high-pitched crying, epicanthal folds, VSD (or other cardiac abnormalities)

Cri-du-chat syndrome (congenital microdeletion of short arm of chromosome 5)

148

distinctive "elfin" facies, MR, hypercalcemia (and sensitivity to vitamin D), well-developed verbal skills and very friendly with strangers, CV problems

William's syndrome (think of Will ferrel in "Elf")
-d/t congenital microdeletion of long arm of chromosome 7 (including elastin gene)

149

90% of pts with DiGeorge syndrome have a deletion where?

22q11 deletion

150

Symptoms of microdeletion at chromosome 22q11:

variable, but includes CATCH-22:
-Cleft palate
-Abnormal facies
-Thymic aplasia (prob with development of 3rd and 4th branchial pouches) --> T-cell deficiency
-Cardiac defects
-Hypocalcemia (d/t parathyroid aplasia)

*see in 90% of DiGeorge pts
*see in Velocardiofacial syndrome (palate, facial, and cardiac defects)

151

List the fat-soluble vitamins

A, D, E, K
-absorption depends on ileum and pancreas
-may have to supplement in CF, sprue, or mineral oil intake (b/c all cause malabsorption/steatorrhea)

152

Water-soluble vitamins

B1
B2
B3
B5
B6
B12
C
Biotin
Folate

153

B-complex deficiencies often result in:

dermatitis, glossitis, diarrhea

154

Which vitamin is:
-retinol
-thiamine
-riboflavin
-niacin
-pantothenate
-pyridoxine
-cobalamin
-ascorbic acid

retinol = vitamin A
thiamine = vitamin B1
riboflavin = vitamin B2
niacin = vitamin B3
pantothenate = vitamin B5
pyridoxine = vitamin B6
cobalamin = vitamin B12
ascorbic acid = vitamin C

155

baby born with cleft palate, cardiac abnormalities. which vitamin may have been in excess in mother?

Vitamin A = retinol
--> in excess has terotegenic effects; so, don't give isoretinoin (acne med) to pregnant women

156

which vitamin may be used to treat measles and AML-M3?

Vitamin A (Retinol)

157

Deficiency in Vitamin A causes night blindness and dry skin. Why?

Vitamin A = constituent of visual pigments in retina; essential for normal differentiation of epithelial cells into specialized tissue.

158

TPP =Thiamine pyrophosphate (Thiamine = B1) = cofactor in what 4 reactions?

1) Pyruvate dehydrogenase (glycolysis)
2) alpha-ketoglutarate dehydrogenase (TCA cycle)
3) Transketolase (HMP shunt)
4) Branched-chain AA dehydrogenase

159

Deficiency in vitamin B1 (Thiamine)?

*impaired glucose breakdown (b/c need TPP as cofactor in glycolysis and TCA cycles, so get ATP depletion); Beriberi (dry/wet), Wernicke-Korsakoff
-malnutrition, alchoholics

160

Wernicke-Korsakoff syndrome

d/t thiamine deficiency
Wernicke: Triad: confusion, ophthalmoplegia, ataxia
Korsakoff: confabulation, personality change, memory loss (permanent)

161

peripheral neuropathy, symmetrical muscle wasting, especially distal muscles; due to a vitamin deficiency

dry beriberi

162

dilated cardiomyopathy (high-output cardiac failure), edema, symmetrical peripheral neuropathy; due to a vitamin deficiency

wet beriberi

163

Cheilosis (inflammation of lips, scaling and fissures at corners of the mouth), Corneal vascularization; what vitamin is deficient?

Vitamin B2 (riboflavin); cofactorin oxidation and reduction (FADH2)

164

Diarrhea, Dermatitis, Dementia; also: glossitis

Pellagra = vitamin B3 (niacin) deficiency

165

symptom of vitamin B3 excess?

Facial flushing (niacin = treatment of choice to increase HDL levels; side effect = facial flushing!)

166

Why may one get a B3 deficiency from:
-Hartnup disease?
-Malignant carcinoid syndrome?
-Isoniazid?

Vit B3 is derived from Tryptophan and requires vitamin B6 for synthesis, so:
-Hartnup disease: have decreased tryptophan absorption, so decreased B3
-malignant carcinoid syndrome: have increased tryptophan metabolism
-Isoniazid: decreased B6 (so, give B6 = pyridoxine to pts on INH!)

167

Which vitamin is an essential component of CoA and fatty acid synthase?

Vitamin B5 = pantothenate ("pento-thenate")

168

What 2 med types may induce vitamin B6 deficiency?

Isoniazid and oral contraceptives

169

Main causes of cobalamin (vit B12) deficiency?

1) Malabsorption: sprue, enteritis, Diphyllobothrium latum
2) no intrinsic factor (pernicious anemia, gastric bypass surgery)
3) no terminal ileum (Crohn's)

*deficiency can cause macrocytic, megaloblastic anemia; neurologic symptoms

170

Schilling test

detect etiology of Vitamin B12 (cobalamin) deficiency

171

Most common vitamin deficiency in US?

folic acid

172

deficiency in folic acid (not in pregnancy/just normal):

macrocytic, megaloblastic anemia (no, neuro symptoms, unlike B12 deficiency)

173

SAM (S-adenosyl-methionine):
-what does it do?
-how is it formed? (what cofactors are needed in its formation)
-what important reaction is it required for?

transfers methyl units!
ATP + Methionine => SAM
*need vitamin B12 and folate to regenerate methionine, and thus SAM
*SAM is required for conversion of NE-->Epinephrine

174

excessive ingestion of raw eggs, may cause what deficiency?

Biotin deficiency! Dute to avidin in eggs, binds biotin

175

Biotin is a cofactor in what 3 reactions:

1) pyruvate carboxylase: (pyruvate-->oxaloacetate)
2) acetyl-CoA carboxylase: acetyl CoA-->malonyl-CoA
3) propionyl-CoA carboxylase: propionyl-CoA-->methylmalonyl-CoA

176

swollen gums, bruising, hemarthrosis, anemia, poor wound healing

scuvry (vit C def; symptoms for collagen synthesis defect)

177

3 functions of vitamin C:

1) hydroxylation of proline and lysine in collagen synthesis
2) helps iron absorption (keeps Fe in a reduced state)
3) conversion of dopamine to NE (dopamine beta-hydroxylase)

178

What forms of vitamin D are these?
D2 =Ergocalciferol
D3 = Cholecalciferol
25-OH D3
1,25-(OH)2D3 = calcitriol

D2 - ingested in plants
D3 - consumed in milk, formed in sun-exposed skin
25-OH-D3 - storage form
1,25-OH2D3 = calcitriol = active form

179

function of vitamin E? Deficiency causes?

function = antioxidant; protects RBCs and membranes from free radical damage
deficiency: hemolytic anemia; weakness, posterior column and spinocerebellar tract demyelination

180

Neonatal hemorrhage with increased PT and increased aPTT, but normal BT? (vit deficiency)

vitamin K deficiency (b/c vit K is synthesized by intestinal flora, but neonatal intestines are sterile, so can't synthesize; give neonates vit K injection after birth)

181

Delayed wound healing, hypogonadism, decreased adult hair (axillary, facial, pubic), ansomia - vit deficiency?

Zinc deficiency

182

Vitamin K is necessary for the synthesis of what heme factors/proteins?

Clotting factors: 10, 9, 7, 2
Proteins C and S
*Warfarin = vit K antagonist

183

Fomepizole

inhibits alcohol dehydrogenase (ehtanol-->acetaldehyde); antidote for methanol or ethylene glycol poisoning

184

Disulfiram - "antibuse"

inhibits acetaldehyde dehydrogenase (acetaldehyde-->acetate); get acetaldehyde accumulation-->hang-over symptoms!

185

How may ethanol lead to hypoglycemia and acidosis?

ethanol metabolism increases the NADH/NAD ratio in the liver, causing: pyruvate-->lactate and Oxaloacetate-->malate
-this inhibits gluconeogenesis and stimulates fatty acid synthesis --> hypoglycemia and hepatic fatty change
-also: overproduction of lactate--> acidosis

186

Kwashiorkor vs Marasmus

Kwashiorkor- protein deficiency; edema (big belly), skin lesions, fatty liver (b/c decreased apolipoprotein synthesis)
Marasmus- malnutrition; muscle wasting, skinny, may have some edema

187

Actions of:
-kinases
-phosphorylase
-phosphatase
-dehydrogenase
-carboxylase

kinases- add a P, uses ATP
phosphorylases - add a P, does not use ATP
phosphotase - removes a P
dehydrogenase - oxidizes
carboxylase - transfers CO2 groups with help of biotin

188

rate limiting enzyme of glycolysis?

PFK-1

189

rate-limiter of gluconeogenesis?

F-1,6-BP

190

rate limiter of TCA cycle?

isocitrate dehydrogenase

191

rate-limiter of glycogen synthesis

glycogen synthase

192

rate-limiter of glycogenolysis

glycogen phosphorylase

193

rate-limiter of HMP shunt

G6PD

194

rate-limiter of de novo pyrimidine synthesis

CMP 2

195

rate-limiter of de novo purine synthesis

glutamine-PRPP amidotransferase

196

rate limiter of urea cycle

CMP 1

197

rate limiter of FA synthesis

ACC (acetyl-CoA carboxylase)

198

rate limiter of FA oxidation

Carnitine acyltransferase I

199

rate limiter of ketogenesis

HMG-CoA synthase

200

rate limiter of cholesterol synthesis

HMG-CoA reductase

201

rate-limiter of heme synthesis

aminolevulinate synthase

202

rate-limiter of bile acid synthesis

7-alpha-hydroxylase

203

Metabolic processes: Glycolysis, Gluconeogenesis, TCA cycle, acetyl-CoA production, HMP shunt, oxidative phosphorylation, Urea cycle, FA oxidation, FA synthesis, protein synthesis, steroid synthesis, heme synthesis:
-which take place in cytoplasm?
-which in mictochondria?
-which in both cytoplasm and mitochondria?

Cytoplasm: Glycolysis, FA synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER)
Mitochondria: FA oxidation, acetyl-CoA production, TCA cycle, oxidative phosphorylation
Both: Heme synthesis, Urea cycle, Gluconeogenesis (HUG :))

204

Which 3 reactions in metabolism require TPP (thiamine cofactor)?

1) Transketolase (HMP shunt: ribulose-5-P --> fructose-6-P)
2) Pyruvate dehydrogenase (glycolysis/acetyl CoA prod: pyruvate--> acetyl CoA)
3) alpha-ketoglutarate dehydrogenase: alpha-ketoglutarate-->succinyl CoA

205

Which 3 metabolic reactions require a biotin cofactor?

1) ACC: acetyl-CoA-->malonyl CoA
2) pyruvate carboxylase: pyruvate-->oxaloacetate
3) propionyl CoA carboxylase: propionyl-CoA-->methylmalonyl CoA

206

which metabolic reaction requires vitamin B12 (cobalamin)?

methylmalonyl-CoA --> succinyl CoA

207

How many ATP are produced per glucose molecule (aerobic in heart/liver; aerobic in muscle; anaerobic)?

Aerobic metabolism via malate aspartate shuttle in heart and liver: 32 ATP/glucose
Aerobic via glycerol-3-phosphate shuttle in muscle: 30 ATP/glucose
Anaerobic: 2 ATP/glucose

208

What do these carriers carry:
-ATP
-NADH/NAD/FADH2
-Coenzyme A
-Lipoamide
-Biotin
-Tetrahydrofolates
-SAM
-TPP

-ATP --> phophoryl groups
-NADH/NAD/FADH2 --> electrons
-coenzyme A --> acyl groups
-lipoamide --> acyl groups
-biotin --> CO2
-tertrahydrofolates --> 1 Carbon units
-SAM --> CH3 groups
-TPP --> Aldehydes

209

NADPH:
-what process is it a product of?
-list 4 processes it is used in:

-NADPH = product of HMP shunt (why G6PD is so important!)
-NADPH is used in:
1) anabolic processes (ie steroid and FA synthesis)
2) respiratory burst (ie in phagolysosomes)
3) P-450
4) glutathione reductase (protects RBCs from oxidative damage by oxygen free radicals)

210

Hexonkinase vs Glucokinase:
-where is it located?
-affinity/km?
-capacity/vmax?
-induced by insulin?
-feedback inhibition on hexokinase/glucokinase?

*both can catalyze glucose --> G-6-P
*Hexokinase:
-ubiquitous
-high affinity/low km
-low capacity/low vmax
-uninduced by insulin

*Glucokinase:
-liver and Beta-cells of pancreas
-low affinity/high km
-high capacity/high vmax
-induced by insulin

*Feedback inhibition:
G-6-P---> inhibits hexokinase
F-6-P ---> inhibits glucokinase
ATP --> inhibits both (AMP stimulates both)
Citrate --> inhibits both

211

Pyruvate dehydrogenase complex: what are the 5 cofactors needed for the 3 enzymes in the complex?

"Tender Loving Care For No one"
1) Thiamine/TPP/B1/Pyrophosphate
2) Liopoic acid
3) CoA (B5;Pantothenate)
4) FAD (B2, riboflavin)
5) NAD (B3, niacin)

***note: same cofactors are used in the alpha-ketoglutarate dehydrogenase complex, in the TCA cycle (alpha-ketoglutarate --> succinyl CoA)

212

Pyruvate dehydrogenase deficiency: what's the treatment?

get lactic acidosis, d/t backup of substrate (pyruvate and alanine)
-treat by intake of ketogenic nutrients: high fat content or lysine and leucine (the only purely ketogenic AA's)

213

What are the 4 fates of pyruvate?

1) Acetyl CoA (enters TCA cycle)
2) Oxaloacetate (replenish TCA cycle, or converted to PEP and used in gluconeogenesis)
3) Lactate (end of anaerobic glycolys: pthwy for RBCs, leukocytes, kidney medulla, lens, testes, cornea)
4) Alanine (carries amino groups to liver from muscle)

214

5 cofactors required for the alpha-ketoglutarate dehydrogenase complex (in the TCA cycle)?

same as for the Pyruvated Dehydrogenase complex!:
-B1
-B2
-B3
-B5
-Lipoic acid

(or, "Tender Loving Care For No one": Thiamine=B1, Lipoic Acid, CoA =B5, FAD =B2, NAD=B3)

215

Electron transport chain: NADH and FADH2 yield how many ATP?

1 NADH --> 3 ATP
1 FADH2 --> 2 ATP

216

In what organ does gluconeogenesis mainly occur?

mostly in liver (also in kidney, intestinal epithelium)

217

Heinz bodies

oxidized hemoglobin precipitated within RBCs; seen in G6PD deficiency

218

Bite cells

result from phagocytic removal of Heinz bodies by splenic macrophages; seen in G6PD deficiency

219

defect in fructokinase

-essential fructosuria
-autosomal recessive
-mild/asymptomatic disease, because fructose doesn't enter cells
-fructose in blood and urine

220

Aldolase B deficiency

-Fructose intolerance
-autosomal recessive
-get accumulation of Fructose-1-Phosphate, so decreased Phosphate availability --> inhibits glycogenolysis and gluconeogenesis
-symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
- treat by decreasing intake of fructose and sucrose

221

Galactokinase deficiency

-mild autosomal recessive disease; get galactose in blood and urine
-infants may have infantile cataracts, and may fail to track objects or develop a social smile

222

absence of Galactose-1-phosphate uridyltransferase

-classic galactosemia
-autosomal recessive
-galactitol accumulates, and may deposit in lens of eyes
-symptoms: FTT, jaundice, hepatomegaly, infantile cataracts; MR; also: pts can't tolerate milk early in life! (b/c lactose = galactose + glucose)
-treat by excluding galactose and lactose from diet

223

infantile cataracts? think:

galactokinase deficiency or classic galactosemia

224

Aldolase reductase

converts glucose to sorbitol.
*some tissues can go on to convert the sorbitol to fructose, via sorbitol dehydrogenase (in liver, ovaries, seminal vesicles)
*other tissues (schwann cells, lens, retina, kidneys) only have aldose reductase, so sorbitol gets trapped in cells --> osmotic damage (ie cataracts, retinopathy, peripheral neuropathy seen in diabetic patients with chronic hyperglycemia)

225

List the essential AAs:

"PVT TIM HALL" = Phe, Val, Thr, Trp, Ile, Met, His, Arg, Leu, Lys

*glucogenic: met, val, arg, his
*glucogenic/ketogenic: ile, phe, thr, trp
*ketogenic: leu, lys

226

which 2 amino acids are required during periods of growth (so many be found in body building supplements)?

Arg and His

227

Lactulose

sweet syrup that can't be digested; used as treatment for hyperammonemia: acidifies the GI and traps NH4+ for excretion

228

orotic acid in blood/urine, decreased BUN, symptoms of hyperammonemia

Ornithine transcarbamoylase deficiency:
-most common urea cycle disorder; X-linked recessive
-can't eliminate ammonia, can't make urea
-excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway!)

229

Why may a B6 deficiency lead to seizures?

B6 is a cofactor in the formation of GABA from Glutamate (via glutamate decarboxylase)
-if B6 deficiency, then decrease GABA (inhibitory), so decreased inhibition --> increased neuroexcitability --> seizures.

230

Deficiency in phenylalanine hydroxylase?

PKU (enzyme that converts phenylalanine-->tyrosine hydroxylase in catecholamine synthesis; without it, get accumulation of phenylalanine and thus excess phenylketones in urine; tyrosine becomes essential)

231

"malignant phenylketonuria" cause?

deficiency/absence of THB (tetrahydrobiopterin cofactor), which is required for phenylalanine hydroxylase to convert Phenylalanine to tryosine, and tyrosine to Dopa

232

MR, growth retardation, seizures, fair skin, eczema, musty body odor

PKU (fair skin, because can't make dopa, and thus can't make melanin, b/c: dopa-->melanin)
-autosomal recessive

233

treatment for PKU

restrict phenylalanine in diet (aspartame); increase intake of tyrosine; also: give THB, if it's deficient.

234

dark connective tissue, brown pigmented sclera, urine turns black after prolonged exposure to air

Alkaptonuria; deficiency in homogentisic acid oxidase (degrades tyrosine-->fumarate)
-autosomal recessive; benign disease

235

Albinism causes? mode of inheritance?

Causes:
-tyrosinase deficiency (can't make melanin from tyrosine) = aut recessive
-defective tyrosine transporters (so decreased tyrosine-->decreased melanin)

236

tall stature, kyphosis, lens subluxation, atherosclerosis (stroke/MI), elevated levels of homocysteine in urine: Causes? Treatment?

-Homocystinuria = autosomal recessive
*Causes:
1) cystathionine synthase deficiency (treat: decrease Met, increased Cysteine, increased B12 and folate)
2) decreased affinity of cystathionine synthase for pyridoxal phosphate (active form of B6) (treat: increased B6 intake)
3) homocysteine methyltransferase deficiency

237

Lens subluxation:

-Marfan's
-Homocysteinuria

238

hexagonal cysteine crystals on urinalysis:

= pathognomonic for cystinuria

239

Cystinuria ("COLA defect")

defect in renal proximal tubules --> decreased reabsorption (so increased secretion) of COLA:
-Cysteine
-Ornithine
-Lysine
-Arginine

*autosomal recessive
*may lead to cystine kidney stones

240

Which amino acids should be avoided in maple syrup urine disease, and why?

Branched AA's: Ile, Leu, Val --> b/c deficiency of alpha-keotacid dehydrogenase, so can't degrade these AAs.

241

Sodium Cyanide-Nitroprusside test

use to dx Cystinuria (causes urine to turn red-purple)

242

What disease may lead to pellagra?

Hartnup disease:
-aut recessive
-tryptophan excretion in urine and decreased absorption from gut; niacin (vit B3) is derived from tryptophan, so get niacin deficiency --> pellagra = diarrhea, dementia, dermatitis, death

243

In which organs/cells does glycogenolysis occur?

Skeletal muscle: glycogen--> glucose; glucose is rapidly metabolized during exercise

Hepatocytes: glycogen--> glucose to maintain blood sugar at appropriate levels

244

Names of the 4 glycogen storage diseases:

"Very Poor Carbohydrate Metabolism"
1) Von Gierkes - type 1 (glucose-6-phosphatase def)
2) Pompes - type 2 (alpha-1,4-glucosidase = acid maltase def)
3) Coris - type 3 (debranching enzyme = alpha-1,6-glucosidase def)
4) McArdles - type 4 (skeletal muscle glycogen phosphorylase def)

245

cardiomegaly and systemic findings leading to early death (by age 3) - which glycogen storage disease and what enzyme is deficient?

Pompe's = type 2
-lysosomal alpha-1,4-glucosidase (acid maltase)

246

severe fasting hypoglycemia, excessive glycogen in liver, increased blood lactate, hepatomegaly

Von Gierkes (type 1) = Glucose-6-Phosphatase deficiency (so can't do gluconeogenesis or glycogenolysis)

247

mild hypoglycemia, glycogen in liver, hepatomegaly, but normal blood lactate (because gluconeogenesis is intact)

Cori's disease = type 3 = debranching enzyme/alpha-1,6-glucosidase deficiency

248

painful muscle cramps, myoglobinuria with strenuous exercise - what glycogen storage disease?

mcardle's - type 5; skeletal muscle glycogen phosphorylase deficiency
--> have increased glycogen in muscle, but can't break it down.
--> does not affect longevity

249

Which lysosomal storage diseases are X-linked recessive? What are the rest?

Fabry's and Hunter's are X-linked recessive
The rest are Autosomal recessive

250

peripheral neuropathy of hands/feet, angiokeratomas, CV/renal disease, alpha-galactosidase A deficiency, ceramide trihexoside accumulation?

Fabry's disease (XR)

251

hepatosplenomegaly, aseptic necrosis of femur, bone crises, macrophages that look like crumpled tissue paper on microscopy, accumulation of glucocerebroside

Gaucher's disease

252

cherry red spot on macula, foam cells on microscopy, neurodegeneration, hepatosplenomegaly, accumulation of sphingomyelin

Niemann-Pick disease ("No man picks his nose with his sphinger!)

253

cherry red spot on macula, lysosomes with onion skin, neurodegeneration, developmental delay, hexosaminidase A deficiency, GM2 ganglioside accumulation

Tay-Sachs (tay saX lacks heXoaminidase)

254

optic atrophy, globoid cells, neuropathy, development delay, galctocerebroside accumulation

Krabbe's disease

255

ataxia and dementia, central and peripheral demyelination, cerebroside sulfate accumulation

Metachromatic leukodystrophy

256

corneal clouding, airway obstruction, gargoylism, hepatosplenomegaly, development delay; heparan sulfate and dermatan sulfate accumulation

Hurler's syndrome

257

aggressive behavior + mild symptoms of Hurler's syndrome (dev'l delay, gargoylism, airway obstruction, hepatosplenomegaly); heparan sulfate and dermatan sulfate accumulation

Hunter's syndrome (XR)

258

Hypoketotic hypoglycemia (+ weakness and hypotonia)

Carnitine deficiency: can't transport LCFAs into mitochondria, so get toxic accumulation in cytoplasm

259

how many kcal from 1 g protein, carb, fat?

1 g protein --> 4 kcal
1 g carb --> 4 kcal
1 g fat --> 9 kcal

260

LCAT = lecithin-cholesterol acyltransferase: what does it do?

takes cholesterol and puts it into HDL particles (catalyzes esterification of cholesterol)

261

CETP = cholesterol ester transfer protein: what does it do?

allows HDL to deposit cholesterol into LDL, etc.. (mediates transfer of cholesterol esters to other lipoprotein particles)

262

Apolipoprotein E

mediates VLDL and chylomicron remanant uptake by liver cells

263

Apolipoprotein A1

activates LCAT (for cholesterol esterification)

264

Apolipoprotein C-11

lipoprotein lipase cofactor (LPL --> degrades TG circulating in chylomicrons and VLDLs)

265

apolipoprotein B-48

mediates chylomicron secretion by the intestine and chylomicron assembly

266

Apolipoprotein B-100

binds LDL receptor (LDL particle uptake by extrahepatic cells)

267

familial dyslipidemia with increased chylomicrons, increased blood TG and cholesterol; pancreatitis, xanthomas...

type 1: hyper-chylomicronemia
-no increase risk for atherosclerosis

268

familial dyslipidemia with increased LDL; atherosclerosis, Achilles xanthomas, corneal arcus; elevated blood cholesterol

type IIa - familial hypercholesterolemia
-aut dominant
-MI by age 20 if homozygous

269

familial dyslipidemia with increased VLDL; increased blood TGS; pancreatitis

type IV - hypertriglyceridemia
-have hepatic overproduction of VLDL

270

corneal clouding, airway obstruction, gargoylism, hepatosplenomegaly, development delay; heparan sulfate and dermatan sulfate accumulation

Hurler's syndrome

271

aggressive behavior + mild symptoms of Hurler's syndrome (dev'l delay, gargoylism, airway obstruction, hepatosplenomegaly); heparan sulfate and dermatan sulfate accumulation

Hunter's syndrome (XR)

272

Hypoketotic hypoglycemia (+ weakness and hypotonia)

Carnitine deficiency: can't transport LCFAs into mitochondria, so get toxic accumulation in cytoplasm

273

how many kcal from 1 g protein, carb, fat?

1 g protein --> 4 kcal
1 g carb --> 4 kcal
1 g fat --> 9 kcal

274

LCAT = lecithin-cholesterol acyltransferase: what does it do?

takes cholesterol and puts it into HDL particles (catalyzes esterification of cholesterol)

275

CETP = cholesterol ester transfer protein: what does it do?

allows HDL to deposit cholesterol into LDL, etc.. (mediates transfer of cholesterol esters to other lipoprotein particles)

276

Apolipoprotein E

mediates VLDL and chylomicron remanant uptake by liver cells

277

Apolipoprotein A1

activates LCAT (for cholesterol esterification)

278

Apolipoprotein C-11

lipoprotein lipase cofactor (LPL --> degrades TG circulating in chylomicrons and VLDLs)

279

apolipoprotein B-48

mediates chylomicron secretion by the intestine and chylomicron assembly

280

Apolipoprotein B-100

binds LDL receptor (LDL particle uptake by extrahepatic cells)

281

familial dyslipidemia with increased chylomicrons, increased blood TG and cholesterol; pancreatitis, xanthomas...

type 1: hyper-chylomicronemia
-no increase risk for atherosclerosis

282

familial dyslipidemia with increased LDL; atherosclerosis, Achilles xanthomas, corneal arcus; elevated blood cholesterol

type IIa - familial hypercholesterolemia
-aut dominant
-MI by age 20 if homozygous

283

familial dyslipidemia with increased VLDL; increased blood TGS; pancreatitis

type IV - hypertriglyceridemia
-have hepatic overproduction of VLDL

284

deficiencies in apo-B100 and apo-B48; FTT, steatorrhea, acanthocytosis, ataxia, night blindness

abetalipoproteinemia --> can't synthesize lipoproteins b/c no apob100 and apob48
-autosomal recessive
-accumulation within enterocytes because can't export absorbed lipid as chylomicrons

285

facial lesions (adenoma sebaceum), hypopigmented ash-leaf spots, coritcal and retinal hamartomas, seizures, MR, renal cysts, renal angiomyolipomas, cardiac rhabdomyomas, increased incidence of astrocytomas

Tuberous Sclerosis (variable presentations)

286

3 mitochondrial disorders:
-Leber hereditary optic neuropathy
-myotonic epilepsy
-MELA

1) Leber Hereditary optic neuropathy --> bilateral vision loss
2) Myoclonic epilepsy with ragged red fibers --> myoclonus, seizures, myopathy assoc with exercise; irregularly shaped muscle fibers on skeletal muscle biopsy
3) MELA = mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes--> seizures, stroke-like episodes with neuro-deficit, muscle weakness, increased serum lactate post-exercise and at rest

287

Hypoglycemia after prolonged fasting, with inappropriately low levels of ketone bodies: What enzyme is deficient?

Impaired Beta-oxidateion/Degradation of Fatty Acids; Acyl-CoA dehydrogenase deficiency

288

antibodies against collagen type 4?

=anti-glomerular basement membrane antibodies --> Goodpasture's syndrome! (hemoptysis + oliguria)...

289

recurrent nosebleeds, and pink spider-like lesions on oral and nasal mucosa, face, and arms.

Osler-Weber-Rendu syndrome = hereditary hemorrhagic telangiectasia

290

How are sugars attached to nitrogen-containing bases in nucleotides?

N-glycosidic bonds
(between sugars-->hydrogen bonds; between nucleotides-->phosphodiester bonds)

291

Which step in collagen synthesis is impaired in pts with scruvy?

Hydroxylation of specific proline and lysine residues on the pro-alpha collagen

292

How does ethanol metabolism contriute to hypoglycemia?

increases NADH/NAD ratio in liver --> so, causes:
*pyruvate--> lactate
-and-
*OAA--> malate

***So, inhibits gluconeogenesis and stimulates hepatic fatty change
***So, get overproduction of lactate-->acidosis; also overproduction of NADPH-->increased fatty acid synthesis

293

What mechanism allows for the production of more than one protein by one human gene?

Alternative splicing