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Flashcards in Steve Harvey's Black and White Biochemistry Facts Deck (257)
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1
Q

Chromatin Structure

A

Negatively charged DNA loops twice around positively charged histones
Histones rich in lysine and arginine
Nucleosome core= H2A, H2B, H3, H4 (two of each)
Histone H1 binds nucleosome and stabilizes nucleosomes

2
Q

Heterochromatin

A

Condensed, transcriptionally inactive, sterically inaccessible
Heterochromatin= highly condensed

3
Q

Euchromatin

A

less condensed, transcriptionally active, sterically accessible
Eu=true “truly transcribed”

4
Q

DNA methylation

A

Template strand cytosine and adenine are methylated in DNA replication, which allows mismatch repair enzymes to distinguish between old and new strands in prokaryotes.
DNA methylation at CpG islands represses transcription
“CpG Methylation Makes DNA Mute”

5
Q

Histone methylation

A

Usually reversibly represses DNA transcription. but can activate it in some cases
“methylation=muting”

6
Q

Histone acetylation

A

Relaxes DNA coiling, allowing for transcription.

“Acetylation=Active”

7
Q

Purines

A

PURe As Gold

Adenine and Guanine

8
Q

Pyrimidine

A

CUT the PY

Cytosine, Thymine, Uracil

9
Q

Adenosine Deaminase Deficiency

A

Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase prevents DNA synthesis and thus decrease lymphocyte count.
One of the major causes of autosomal recessive SCID

10
Q

Lesch-Nyhan syndrome

A

HGPRT
Hyperuricemia - if guanine and hypoxanthine cannot be phosphorylated by HGPRT, they get turned into urea which causes gout (see yellow crystals in their shit).

pissed off, retardation, DysTonia
HGPRT .

(hypoxanthine to IMP and guanine to GMP)

X-linked recessive
Treatment: allopurinol or febuxostat

Patient can develop macrocytic anemia because folate and b12 can compensate to make up for lost purines

11
Q

DNA replication: Helicase

A

Unwinds DNA template at replication fork

12
Q

DNA polymerase III

A

prokaryotes only
Elongates leading strand by adding DNA to the 3’ end
proofreads with 3’ to 5’ exonuclease

13
Q

DNA polymerase I

A

Prokaryotes only
Degrades RNA primer (via RNAse H), replaces it with DNA
Same as polymerase III but excises RNA primer with 5’ to 3’ exonuclease

14
Q

DNA ligase

A

Catalyzes the formation of a phosphodiester bond within a strand of double-stranded DNA (joins okazaki fragments)

15
Q

Telomerase

A

RNA-dependent DNA polymerase that adds DNA to 3’ ends of chromosomes to avoid loss of genetic material with every duplication

16
Q

DNA mutations: Transition vs transversion

A

Transition- purine to purine or pyrimidine to pyrimidine

Transversion- purine to pyrimidine or vise versa

17
Q

Silent mutation

A

nucleotide substitution but codes for same amino acid: often base change in 3rd position of codon (tRNA wobble)

18
Q

Missense

A

Nucleotide substitution resulting in changed amino acid (called conservation if new amino acid is similar in chemical structure)
example: sickle cell disease

19
Q

Nonsense

A

Nucleotide substitution resulting in early stop codon

“Stop the nonsense”

20
Q

Frameshift

A

Deletion or insertion of a number of nucleotides not divisible by 3, resulting in misreading of all nucleotides downstream, usually resulting in a truncated, nonfunctional protein
Example: Duchenne muscular dystrophy

21
Q

Nucleotide excision repair

A

specific endonucleases release the oligonucleotide containing damaged bases; DNA polymerase and ligase fill and reseal the gap, respectively. Repairs bulky helix-distorting lesions.
example: xeroderma pigmentosum, prevents repair of pyrimidine dimers because of ultraviolet light exposure

22
Q

Mismatch repair

A

Newly synthesized strand is recognized, mismatched nucleotides are removed and the gap is filled and resealed
example: defective in hereditary nonpolyposis colorectal cancer and lynch syndrome (marshawn lynch is a mismatch or some shit)

23
Q

Non homologous end joining

A

Brings together 2 ends of DNA fragments to repair double-stranded breaks, No requirement for homology
Mutated in ataxia telangiectasia

24
Q

DNA/RNA protein synthesis direction

A

DNA and RNA are read in the 3’ to 5’ diraction

DNA and RNA are both synthesized 5’ to 3’
Drugs blocking DNA replication often have modified 3’ OH, preventing addition of the next nucleotide (chain termination)

25
Q

mRNA start codons

A

AUG (or rarely GUG)

eukaryotes: codes for methionine
prokaryotes: codes for formylmethionine (f-met)

26
Q

mRNA stop codons

A

UGA (U Go Away)
UAA (U Are Away)
UAG (U Are Gone)

27
Q

RNA polymerases

A
Eukaryotes
RNA polymerase 1: makes rRNA
RNA polymerase 2: makes mRNA
RNA polymerase 3: makes tRNA
Prokaryotes
1 RNA polymerase makes all 3 kinds of DNA
28
Q

RNA processing

A

initial transcript is called heterogenous nuclear RNA (hnRNA)
Processing: capping 5’ end (7-methylguanosine cap), Polyadenylation of 3’ end, splicing out of introns

29
Q

Splicing of pre-mRNA

A
  1. Primary transcript combines with snRNPs and other proteins to forms spliceosome
  2. Lariat-shaped (looped) intermediate is generate
  3. Lariat is released to precisely remove intron and join 2 exons
    antibodies to spliceosomal snRNPs (anti-smith antibodies) are highly specific for SLE
    Anti-U1 RNP antibodies are highly associated with mixed connective tissue disease
30
Q

tRNA: T-arm and D-arm

A

T-arm: contains the sequence for tRNA-ribosome binding
D-arm: contains dihydrouracil acid for recognition by the correct aminoacyl-tRNA synthetase
3’ CCA is the amino acid acceptor site

31
Q

Golgi does what

A

modifies N-oligosaccharides on asparagine
adds o-oligosaccharides on serine and threonine
adds mannose-6-phosphate to proteins for trafficking to lysosomes

32
Q

I-Cell disease (Inclusion cell disease)

A

inherited lysosomal storage disorder
defect in phosphotransferase leading to failure of the golgi to phosphrylate mannose residues on glycoproteins leading to proteins that are secreted extracellularly rather than delivered to the lysosome

coarse facial features, clouded cornea, restricted joint movement,

small, thin, lethargic, and high plasma levels of lysosomal enzymes (hydrolases and glycosylases).
Fatal in childhood

33
Q

Signal Recognition Particle

A

Abundant cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER.

34
Q

COPI

A

Golgi to golgi trafficking (retrograde)

Golgi to ER

35
Q

COPII

A

Golgi to golgi trafficking (anterograde)

Er to Golgi

36
Q

Clathrin

A

Trans-golgi to lysosome

Plasma membrane to endosomes (receptor mediated endocytosis like LDL receptor)

37
Q

Proteasome

A

Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins. Defects in the ubiquitin-proteasome system are implicated in Parkinson disease.

38
Q

Microtubule

A

Cylindrical structure composed of a helical array of polymerized heterodimers of α- and β-tubulin. Each dimer has 2 GTP bound.
Incorporated into flagella, cilia, mitotic spindles. Grows slowly, collapses quickly.
Also involved in slow axoplasmic transport in neurons.
Molecular motor proteins—transport cellular cargo toward opposite ends of microtubule tracks.
Dynein—retrograde to microtubule (+ Žto −).
Kinesin—anterograde to microtubule (− to Ž +).

39
Q

Drugs that act on microtubules

A

Microtubules Get Constructed Very Poorly

mebendazole, Griseofulvin, Colchicine, Vincristine/Vinblastine, Paclitaxel

40
Q

Cilia structure

A

9+2 arrangement of microtubules
Axonemal dynein- ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.

41
Q

Kartagener syndrome

A

primary ciliary dyskinesia
immotile cilia due to a dynein arm defect
results in male and female infertility due to immotile sperm and dysfunctional fallopian tube cilia, respectively; increase risk of ectopic pregnancy. Can cause bronchiectasis, recurrent sinusitis, and situs inversus

42
Q

What are the stains for intermediate fillaments:

 TYPE
Connective tissue
Muscle
Epithelial cells
NeuroGlia
Neurons
A
Connective tissue: Vimentin
Desmin: Muscle
Cytokeratin: Epithelial cells
GFAP: Neuroglia
Neurofilaments: neurons
43
Q

Oubain does what

A

inhibits Na/K channel by binding to K+ site

44
Q

Type 1 Collagen

A

Most common
Bone (made by osteoblasts)
Skin, Tendon, dentin, fascia, cornea, late wound repair
Type I: Bone (decrease production in osteogenesis imperfecta type I);
from fibroblasts and osteoblasts

45
Q

Type II Collagen

A

Cartilage (including hyaline), vitreous body, nucleus pulposus;
Type II: cartwolage;
Made from chondrocytes

46
Q

Type III Collagen

A

Skin, blood vessels, uterus, fetal tissue, granulation tissue
deficient in the uncommon vascular type of ehlers danlos syndrome;
made from smooth muscle cells and endothelial cells

47
Q

Type IV Collagen

A

Basement membrane, basal lamina, lens
Defective in Alport syndrome, targeted by autoantibodies in Goodpasture syndrome;
made from endothelial and epithelial cells

48
Q

Collagen synthesis Steps

A
  1. Synthesis (RER)
  2. Hydroxylation (RER)- requires Vit C
  3. Glycosylation (RER)- Problems forming triple helix leads to osteogenesis imperfecta
  4. Exocytosis
  5. proteolytic processing
  6. crosslinking- problem here leads to Ehlers-Danlos
49
Q

Osteogenesis Imperfecta

A

Genetic disorder, most commonly autosomal dominant which leads to decreased production of other wise normal type 1 collagen (won’t hydroxylate on prolines and lysines)
Blue sclera due to the translucency of the connective tissue over the choroidal veins
PROGRESSIVE hearing loss (abnormal ossicles)
dental problems due to lack of dentin

50
Q

Ehlers Danlos Syndrome

A

Faulty collagen syntheses causing hyperextensible skin, tendency to bleed and bruise and hypermobile joints
6+types, inheritance and severity vary, autosomal dominant or recessive
Associated with joint dislocation, berry and aortic aneurysms, organ rupture
Hypermobile type: most common (lysyl hydroxylase deficiency)
classical type: mutation in type V collagen (joint and skin problems)
Vascular type: deficient type III collagen

51
Q

Menkes Disease

A

X linked recessive defect in ATP7A gene
Connective tissue disease caused by impaired copper absorption and transport.
leads to decreased activity of lysyl oxidase (copper is cofactor)
brittle kinky hair (called kinky hair disease), growth retardation, hypotonia

52
Q

Elastin

A

rich in proline and glycine, nonhydroxylated forms
tropoelastin with fibrillin scaffolding
cross-linking takes place extracellularly and gives elastin its elastic properties
broken dwon by elastase, which is normally inhibited by alpha 1 antitrypsin

53
Q

Wrinkles in aging are due to

A

decrease collagen and elastin production

54
Q

Emphysema and elastin

A

Emphysema can be caused by alpha 1 antitrypsin deficiency resulting in excess elastase

55
Q

Southern blot

A

Works with DNA

DNA is broken up, run on gel, denatured, radiolabeled, and then anneals to its complementary strand which is visualized

56
Q

Northern blot

A

Works with RNA;
useful in studying mRNA levels;
Take mRNA and use P-cDNA probe to label it, can tell size and abundance

57
Q

Western Blot

A

Sample proteins are separated on gel and labeled with antibodies;
Confirmatory test for HIV after a positive ELISA;
useful for identification and sizing of protein

58
Q

Southwestern Blot

A

Identifies DNA-binding proteins like transcription factors

uses labeled oligonucleotide probes; uses P-cDNA probes like northern blots, but is looking at DNA protein interaction.

59
Q

Indirect ELISA

A

Use a test antigen to see if a specifc antibody is present in the sample
a secondary antibody that glows is added to detect the first antibody

60
Q

Direct ELISA

A

uses antibody to see if a specific antigen is present in the sample
a secondary antibody is coupled to a glowing enzyme that is added to detect the antigen

61
Q

examples of codominance

A

Blood groups

Alpha 1 antitrypsin deficiency

62
Q

Pleiotropy

A

one gene contributes to multiple phenotypic effects

PKU manifests with light skin, intellectual disability, and musty body odor

63
Q

Dominant Negative Mutation

A

Exerts a dominant effect. A heterozygote prodeuces a nonfunctional altered protein that also prevents the normal gene product from functioning

64
Q

Linkage disequilibrium

A

Tendency for certain alleles at 2 linked loci to occur together more often that expected by chance.
measured in a population, not in a family, varies by population

65
Q

Mosaicism

A

Presence of genetically distinct cell lines in the same individual
Somatic mosaicism- mutation propagates through multiple tissues and organs
Gonadal mosaicism- mutation only in egg or sperm cells

66
Q

McCune-Albright syndrome- genetics

A

Lethal disease if the mutation is somatic, survivable if the mutation is mosaic

67
Q

Locus Heterogeneity

A

Mutations at different loci make the same phenotype

albinism

68
Q

Allelic Heterogeneity

A

Different mutations in the same locus produce the same phenotype

69
Q

Heteroplasmy

A

Presence of both normal and mutated mtDNA resulting in variable expression in mitochondrial inherited disease.

70
Q

Uniparental disomy

A

Offspring receive 2 copies of a chromosome from 1 parent and 0 from the other
Heterodisomy indicates a meiosis 1 error
Isodisomy indicates a meiosis II error

71
Q

Imprinting

A

at some loci, only one allele is active, the other is inactive. With one allele inactivated, deletion of the active allele leads to disease state

72
Q

Prader-Willi Syndrome

A

Maternal imprinting: gene from mom is normally silent and paternal gene is deleted/mutated
Results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia
25% of cases due to paternal uniparental disomy (means two paternal genes received, both imprinted, no maternal genes)
Chromosome 15

73
Q

Angelman Syndrome

A

Paternal imprinting: gene from dad is normally silent and maternal (chromosome 15)gene has micro deletion
results in inappropriate laughter, seizures, ataxia, severe intellectual disability
5% of cases due to paternal uniparental dismony

an angel of a man is silent
the kids are known as “happy puppets”

74
Q

Autosomal dominant polycystic kidney disease

A

Autosomal dominant
bilateral massive enlargement of kidneys due to multiple large cysts
85% due to mutation in PKD1 (chromosome 16) (16 letters in “polycystic kidney”)
15% due to mutation in PKD2 (chromosome 4)

75
Q

Familial adenomatous polyposis

A

Autosomal dominant
Colon becomes covered with adenomatous polyps after puberty. progresses to colon cancer if not removed
Mutation in chromosome 5 (apc gene) (polyp=5)
APC is tumor suppressor gene

fap with your hand (five fingers, chromosome 5)

76
Q

Familial hypercholesterolemia

A

Autosomal dominant
elevated LDL due to defective or absent LDL receptor (no receptor mediated endocytosis)
leads to severe atherosclerotic disease early in life and tendon xanthomas (usually in achilles tendon)

77
Q

Hereditary hemorrhagic telangiectasia

A

Autosomal dominant
inherited disorder of blood vessels
telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations, GI bleeding, hematuria
AKA Osler-Weber-Rendu syndrome

78
Q

Hereditary Spherocytosis

A

Autosomal dominant
spheroid erythrocytes due to spectrin or ankyrin defect
hemolytic anemia, increase MCHC (mean cellular hemoglobin concentration)
treat with splenectomy

79
Q

Huntingtons disease

A

Autosomal dominant
depression, progressive dementia, choreiform movements, caudate and putamen atrophy, and decrease levels of GABA and ACh in the brain
gene on chromosome 4, trinucleotide repeat disorder (CAG)
increase # of repeats leads to younger age of onset

80
Q

Marfan syndrome

A

Autosomal dominant
Fibrillin-1 gene (FB1) mutation leading to connective tissue disorder affecting skeleton, heart, and eyes;
Tall, long extremities, pectus excavatum, hypermobile joints, long tapered fingers and toes, cystic medial necrosis of aorta leading to aortic incompetence and dissecting aortic aneurysms, floppy mitral valve, subluxation of the lenses

81
Q

Multiple Endocrine Neoplasms (MEN)

A

Autosomal dominant
several distinct syndromes (1, 2A, 2B) characterized by familial tumors of endocrine glands, including pancreas, parathyroid, pituitary, thyroid, and adrenal medulla
MEN 2A and 2B are associated with ret gene - encodes receptor tyrosine kinase

RET MEN

82
Q

Neurofibromatosis type 1

A

Neurocutaneous disorder characterized by cafe-au-lait spots and cutaneous neurofibromas
Autosomal dominant, 100% penetrance, variable expressivity, NF1 gene on chromosome 17

NF1 is a tumor suppressor gene. It normally encodes for a GAP (GTP-ase activating protein). GAPs suppresses RAS activity by making RAS hydrolyse GTP to GDP faster, reducing the amount of time RAS is in the “on” state.

83
Q

Neurofibromatosis type 2

A

Autosomal dominant
Bilateral acoustic schwannomas, juvenile cataracts, meningiomas (meninges is dura, arachnoid, and pia mater), and ependymomas (tumor on the epithelial-like lining of the ventricular system)

NF2 gene on chromsome 22q (type 2=22)

84
Q

Tuberous Sclerosis

A

Autosomal dominant
Neurocutaneous disorder with multi-organ involvement
numerous benign hamartomas
incomplete penetrance, variable expressivity

85
Q

Von Hippel-Lindau Disease

A

Autosomal dominant
Disorder characterized by development of numerous tumors (cerebellar hemangioblastoma, renal cell adenoma, BILATERAL renal cell carcinoma, pheochromocytoma)
associated with deletion of VHL gene (tumor suppressor) on chromosome 3 (3p) (3 letters in VHL and RCC)

VHL gene normally inhibits hypoxia inducible factor 1 alpha (HIF1alpha normally is degraded when there is oxygen present)
VHL protein is a component of ubiquitin ligase

86
Q

Cystic Fibrosis-genetics

A

Autosomal recessive

defect in CFTR gene on chromosome 7, deletion of Phe508 most common

87
Q

Cystic Fibrosis-Pathophysiology

A

CFTR gene encodes an ATP-gated Cl- channel that secretes Cl into lungs and GI and resorbs Cl in sweat glands
Mutation causes misfolded protein, stays in RER, decrease Cl secretion and H2O, increased Na reabsoprtion, thick mucus

88
Q

Cystic Fibrosis-diagnosis

A

increase Cl and Na concentration in sweat is diagnostic

can have contraction alkalosis, and hypokalemia

89
Q

Cystic Fibrosis- Complications

A

Recurrent pulmonary infections (pseudomonas)
chronic bronchitis and bronchiectasis–> reticulonodular pattern on CXR, pancreatic insufficiency, malabsorption and steatorrhea, nasal polyps, meconium ileus in newborns, infertility in males (no vas deferens or sperm)
Fat soluble vitamin deficiencies (A, D, E, K)

90
Q

Cystic Fibrosis-treatment

A

N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds within mucus glycoproteins), dornase alfa (DNAse) to clear leukocytic debris

also the antidote for acetaminophen overdose

91
Q

Duchenne Muscular Dystrophy

A

X-lined frameshift mutation–> truncated dystrophin protein –> accelerated muscle breakdown
Weakness begins in pelvic girdle muscles and progresses superiorly
Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle –> Gower maneuver
Onset before 5 years
Dilated cardiomyopathy is common cause of death
Duchenne= Deleted Dystrophin
Increased CPK, western blot and muscle biopsy diagnostic

92
Q

Function of Dystrophin gene

A

DMD gene is longest coding region in human genome
increase chance of spontaneous mutation
dystrophin helps anchor muscle fibers, primarily in skeletal and cardiac muscle. connects intracellular actin to transmembrane proteins alpha and beta-dystroglycan which connect to the extracellular matrix

93
Q

Becker Muscular Dystrophy

A

Usually X-linked point mutation in dystrophin gene without frameshift
less severe than Duchenne
onset in early adolescence or early adulthood
Deletions can cause both Becker and Duchenne

94
Q

Myotonic Type 1 muscular dystrophy

A

CTG trinucleotide repeat expansion in the DMPK gene –> abnormal expression of myotonin protein kinase –> myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmia
CTG repeat mutation

95
Q

Fragile X syndrome

A

X-linked dominant defect affecting the FMR1 gene (Fragile x Mental Retardation), CGG trinucleotide repeat mutation
2nd most common intellectual disability
post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, mitral valve prolapse, aortic root dilation
Xtra large testes, jaw, ears

96
Q

Down syndrome

A

trisomy 21, nondisjunction of homologous chromosomes, huge increase if mom over 45
flat facies, intellectual disability, prominent epicanthal folds, single palmar crease, gap between 1st two toes, duodenal atresia, hirschsprung disease, congenital heart disease (atrial septal defect), Brushfield spots

97
Q

Down Syndrome-Increase risk of

A

Increase risk of ALL, AML, alzheimer disease (>35), Atrial septal defects

98
Q

Down Syndrome- findings in 1st trimester

A

increase nuchal translucency and hypoplastic nasal bone, serum PAPP-A is decreased, free beta-hCG is increased

99
Q

Down Syndrome- Findings in 2nd trimester

A

quad screen shows: decrease alpha-fetoprotein, increase beta-hCG, decrease estriol, increased inhibin A

100
Q

Edwards Syndrome

A

Trisomy 18
severe intellectual disability, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart and kidney disease.
Die in first year

101
Q

Edwards findings before birth

A

PAPP-A and free beta-hCG are decreased in first trimester

Quad screen shows: decrease alpha-fetoprotein, decreased beta-hCG, decrease estriol, decreased or normal inhibin A

102
Q

Patau Syndrome

A

Trisomy 13
intellectual disability, rocker bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease Death in first year

103
Q

Patau syndrome findings before birth

A

decreased beta-hCG, decreased PAPP-A, and increase nuchal translucency

104
Q

How does APC gene work

A

tumor suppressor gene
promote degradation of catenin protein (catenin promotes proliferation and works with cell adhesion) by phosphorylating catenin via the GSK3b
lose APC–> less catenin degradation –> cell proliferation

autosomal dominant mutation of APC gene results in FAP

APC tears APpart Catenin

FAPping is as easy as A.P.C. (A Penis Clench)

105
Q

Mycophenolate mofetil

A

immunosuppressive

inhibit IMP dehydrogenase which turns IMP into GMP, stopping the synthesis of guanine nucleotide (purine)

106
Q

Microvilli

A

Contain Microfilaments which have actin and myosin in them

Does not contain microtubules! (aka microvilli are not cilia)

107
Q

Robertsonian translocation

A

Occurs when the long arms of 2 acrocentric chromosomes (chromosomes with centromeres near their ends) fuse at the centromere and the 2 short arms are lost. balanced translocations do not cause problems, unbalanced causes miscarriage, stillbirth, and chromosome imbalances (downs syndrome, patau syndrome)
usually happens in chromosomes 13, 14, 15, 21, 22

108
Q

cri-du-chat syndrome

A

congenital microdeletion of the chromosome 5
microencephaly, moderate to severe intellectual disability, high pitched crying/mewing, epicanthal folds, cardiac abnormalities (CVD) are common

109
Q

Williams syndrome

A

congenital microdeletion of long arm of chromosome 7 (deletes elastin gene)
distinctive elfin facies, intellectual disability, hypercalcemia (increase sensitivity to Vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems.

Robin williams was extremely friendly, and the rope he used to hang himself was not very elastic (i’m so sorry)

110
Q

22q11 deletion syndromes

A

CATCH-22
Variable presentation with Cleft palate, Abnormal facies, Thymic aplasia–> t cell deficiency, Cardiac defects, Hypocalcemia secondary to parathyroid aplasia

111
Q

DiGeorge Syndrome

A

Thymic, parathyroid, and cardiac defects

aberrant development of 3rd and 4th pouches–> T-cell deficiency (no thymus) and hypocalcemia (no parathyroid)

112
Q

Vitamins that are fat soluble

A

A, D, E, K
absorption dependent on gut and pancreas. Toxicity higher in fat than water soluble due to accumulation in fat
Steatorrhea syndromes (CF, sprue) cause deficiency

113
Q

Water soluble Vitamins

A

B1, 2, 3, 5, 6, 7, 9, 12
C
all wash out easily from body except B12 and B9 which are stored in the liver

114
Q

Vitamin A: function

A

also called retinol
involved in: visual pigments (retina), normal differentiation of epithelial cells into specialized cells, prevents squamous metaplasia, used to treat measles and AML
Found in liver and leafy veggies

115
Q

Vitamin A: deficiency

A

night blindness (nyctalopia) dry, scaly skin (xerosis cutis) alopecia, corneal degeneration (keratomalacia), immune suppression

116
Q

Vitamin A: excess

A

Arthralgias, skin changes (scaliness), alopecia, cerebral edema, psuedotumor cerebri, osteoporosis, hepatic abnormalities
**teartogenic (cleft palate, cardiac problems): this is why you need negative pregnancy tests before giving isotretinoin for acne

117
Q

Vitamin B1: Function

A

Thiamine
in thiamine pyrophosphate (TPP)
Cofactor for: pyruvate dehydrogenase, alpha keoglutarate dehydrogenase, Transketolase, branched chain ketoacid dehydrogenase

118
Q

Vitamin B1: deficiency

A
Thiamine
impaired glucose breakdown
Wernicke-Korsakoff Syndrome
Seen in malnutrition and alcoholism
diagnose by giving B1 and seeing if RBC transketolase activity goes up.
Beri-Beri, dry and wet
119
Q

Dry Beri-Beri

A

B1 thymine deficiency

Polyneuritis, symmetrical muscle wasting

120
Q

Wet Beri-Beri

A

Hight output cardiac failure (dilated cardiomyopathy), edema

121
Q

Vitamin B2: function

A

Riboflavin
Component of Flavins (FAD, FMN)
used as cofactors in redox reactions
e.g. succinate dehydrogenase reaction in TCA cycle

122
Q

Vitamin B2: deficiency

A

Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)
Corneal Vascularization
the Two C’s of B2

123
Q

Vitamin B3: function

A
Niacin
Constituents of NAD and NADP
Derived from tryptophan 
synthesis requires vitamins B2 and B6
Used to treat dyslipidemia (lowers levels of VLDL and raises HDL)
Nad derived from Niacin

too much causes flushing

124
Q

Vitamin B3: Deficiency

A

Niacin
glossitis, pellagra
The three Ds - Dermatitis (dry skin) Diarrhea, Dementia

BEEFY red tounge with no chelosis

Deficiency from Hartnup disease (decrease tryptophan absorption), malignant carcinoid syndrome (increased tryptophan metabolism), isoniazid (decrease vitamin B6)

125
Q

Vitamin B3: Excess

A

Facial flushing (induced by prostaglandins), hyperglycemia, hyperuricemia

126
Q

Pellegra

A

Diarrhea, Dementia (also hallucinations), Dermatitis

Vitamin B3 deficiency

127
Q

Vitamin B5

A

Pantothenate (5 is Pento)
Essential component of conenzyme A (CoA) and fatty acid synthase
Deficiency causes dermatitis, enteritis, alopecia, adrenal insufficiency

128
Q

Vitamin B6: function

A

Pyridoxine
Converted to pyridoxal phosphate, a cofactor used in transamination (e.g. ALT, AST), glycogen phosphorylase, synthesis of cystathionine, heme, niacin, histamine, neurotransmitters (serotonin, epi, NE, dopamine, and GABA)

129
Q

Vitamin B6: Deficiency

A

Pyridoxine
Convulsions, hyperirritability, peripheral neuropathy (can be from isoniazid and oral contraceptives), sideroblastic anemias due to impaired hemoglobin synthesis and iron excess

130
Q

Vitamin B7: function

A

Biotin

Cofactor for 1 carbon transfers: pyruvate carboxylase, acetyl-Coa carboxylase, propionyl-CoA carboxylase

131
Q

Vitamin B7: Deficiency

A

Relatively rare. Avidin in egg whites avidly binds biotin, some antibiotics
Dermatitis, alopecia, enteritis

132
Q

Vitamin B9: function

A

Folic acid
converted to tetrahydrofolate (THF) a coenzyme for 1-carbon transfer/methylation reactions
important for the synthesis of nitrogenous bases in DNA and RNA
Folate found in foliage
Absorbed in the jejunum

133
Q

Vitamin B9: deficiency

A

Macrocytic, megaloblastic anemia
Hypersegmented PMNs
glossitis, no neuro symptoms (separates it from B12)
Labs: increased homocysteine, normal methylmalonic acid. Most common vitamin deficiency in USA. Seen in alcoholics and pregnant women.

most common vitamin deficiency in US

134
Q

Vitamin B12: Function

A

Cobalamin
Cofactor for homocysteine methyltransferase and methylmalonyl-CoA mutase
Found in animal products
stores in body last years, only decreased in vegans or absorption problem, or intrinsic factor deficiency, or no terminal ileum like in Crohns.

135
Q

Vitamin B12: deficiency

A

Macrocytic megaloblastic anemia
hypersegmented PMNs
paresthesias, subacute combine degeneration (degeneration of dorsal columns and lateral corticospinal and spinocerebellar tracts) due to abnormal myelin
Associated with increased serum homocysteine and methylmalonic acid levels. prolonged deficiency causes irreversible nerve damage.

136
Q

Vitamin C: Function

A

Ascorbic Acid
antioxidant
facilitates iron absorption (makes it Fe2)
needed for hydroxylation of proline and lysine in collagen synthesis
needed for dopamine Beta hydroxylase which converts dopamine to NE

137
Q

Vitamin C: Deficiency

A

Scurvy: swillen gums, bruising, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages and corkscrew hair
weakened immune system

138
Q

Vitamin C: Excess

A

Nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasis, can increase iron toxicity in predisposed people (transfusion patients, hereditary hemochromatosis)

139
Q

Vitamin D: Storage form and Active form

A

Storage: 25OH D3
Active: 1,25-(OH)2 D3 (calcitriol)

140
Q

Vitamin D: function

A

increase intestinal absorption of Calcium and phosphate

Increase Bone mineralization

141
Q

Vitamin D: deficiency

A

Rickets in kids, osteomalacia in adults, hypocalcemia tetany. Breastfed infants should get Vitamin D. Made worse by low light exposure, pigmented skin, prematurity

142
Q

Vitamin D: Excess

A

Hypercalcemia, hypercalciuria, loss of appetite, stupor, Seen in sarcoidosis (increase activation of vitamin D by epitheliod macrophages

143
Q

Vitamin E

A

Tocopherol/tocotrienol
Antioxidant (protects erythrocytes from free radicals)
Enhances warfarin effects
Deficiency: heeeemolytic aneeeemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demylenation

144
Q

Vitamin K

A

Cofactor for gama-carboxylation of glutamic acid residues on various proteins required for blood clotting. Synthesized by intestinal flora.
Needed to activates factors II, VII, IX, X, and protein C and S
Deficiency: Neonatal hemorrhages with increased PT and increased aPTT but normal bleeding time (have sterile intestines, can’t make K), also after long course of antibiotics

145
Q

Zinc

A

Essential for the activity of 100+ enzymes. important in the formation of zinc fingers (transcription factor motif)
Deficiency: delayed wound healing, hypogonadism, decreased adult hair (Axillary facial, pubic), dysgeusia, anosmia, acrodermatitis enteropathica
May predispose to alcoholic CIRRHOSIS

146
Q

Ethanol Metabolism

A

Ehtanol coverted to acetaldehyde via the alcohol dehydrogenase (turns NAD into NADH), in cytosol
Acetaldehyde is converted to acetate via the acetaldehyde dehydrogenase (turns NAD into NADH), happens in mitochondria
Increases NADH/NAD ratio in liver

147
Q

Increase in NADH/NAD ratio (as seen with ethanol) causes

A
lactic acidosis (pyruvate goes to lactate)
Fasting hypoglycemia (Oxaloacetate goes to malate and stops gluconeogenesis)
Hepatosteatosis (glyceraldehyde 3 phosphate goes into glycerol 3-phosphate and combines with FAs to make triglycerides)
Shuts down TCA cycle and creates ketoacidosis and hepatosteatosis
148
Q

Kwashiorkor

A

Protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty due to decrease apolipoprotein). clinical picture is small child with swollen belly
Kwashiorkor=MEAL

149
Q

Marasmus

A

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

150
Q

Rate limiting step of Glycolysis

A

Phosphofructokinase-! (PFK-1)
increased by AMP and Fructose 2,6 bisphosphate
decreased by ATP and citrate

151
Q

Rate limiting step of gluconeogenesis

A

Fructose-1,6-bisphosphatase
increased by ATP and acetyl-CoA
decreased by AMP and fructose 2,6, bisphosphate

152
Q

TCA cycle rate limiting step

A

Isocitrate Dehydrogenase
increased by ADP
Decreased by ATP and NADH

153
Q

Glycogenesis rate limiting step

A

Glycogen synthase
increased by glucose-6-phosphate, insulin, cortisol
decreased by EPI and glucagon

154
Q

Glycogenolysis rate limiting step

A

Glycogen phosphorylase
increased by EPI, Glucagon, and AMP
Decreased by Glucose-6-phosphate, insuling, ATP

155
Q

HMP shunt rate limiting step

A

Glucose-6-Phosphate Dehydrogenase (G6PD)
increased by NADP
decreased by NADPH

156
Q

Pyrimidine synthesis rate limiting step

A

Carbamoyl Phosphate Synthetase II

157
Q

Purine syntheses rate limiting step

A

Glutamine-phosphoribosylpyrophosphate amidotransferase (PRPP)
Decreased by AMP, Inonsine monophosphate (IMP), GMP

158
Q

Urea cycle limiting step

A

Carbomoyl phosphate synthetase I

increased by N-acetylglutamate

159
Q

Fatty acid synthesis rate limiting step

A

acetyl-CoA Carboxylase
increased by insulin, citrate
decreased by glucagon and palmitoyl-CoA

160
Q

Fatty acid oxidation rate limiting step

A

Carnitine acyltransferase I

decreased by Malonyl-CoA

161
Q

Ketogenesis rate limiting step

A

HMG-CoA synthase

162
Q

Cholesterol rate limiting step

A

HMG-CoA reductase
increased by insulin and thyroxine
decreased by glucagon and cholesterol

163
Q

Familial Hypocalciuria hypercalcemia

A

CaSR (calcium sensing receptor) has decreased sensitivity leading to decreased feedback to parathyroid hormone
Get increased PTH, increased serum Ca, and decreased Ca in 24hr urine
Gene on Chromosome 3q

164
Q

Can fatty acids be gluconeogenic

A

It makes acetyl-coa so no it is not gluconeogenic.

Glycerol, the backbone of triglycerides, can be made into glycerol-3-phosphate so it is gluconeogenic.

165
Q

Anaerobic glycolysis VS aerobic glycolysis: ATP production

A

Aerobic= 32ATP

anaerobic=2 atp

166
Q

Net glycolysis in the cytoplasm

A

in: glucose+2 Pi+2 ADP+2 NAD
out: 2 pyruvate+2ATP+2NADH+2H+2H2O

167
Q

What glycolysis steps require ATP as the input

A

glucokinase/hexokinase

Phosphofruckinase-1 (PFK-1)

168
Q

What glycolysis steps create ATP

A

Phosphoglycerate kinase

Pyruvate Kinase

169
Q

Electron transport chain and oxidative phosphorylation: complexes and what blocks them

A

Complex 1: NADH turned into NAD, blocked by Rotenone
Complex 2: turns FADH2 into FAD
Complex 3: blocked by antimycin
Complex 4: 1/2O2+2H–>H2O, blocked by Cyanide
Complex 5: ADP+Pi–>ATP, blocked by Oligomycin

170
Q

Oligomycin

A

Blocks Complex 5 of ETC

Directly stops synthesis of ATP

171
Q

Glucose-6-phosphate dehydrogenase deficiency

A

x-linked recessive disorder, most common human enzyme deficiency
more prevalent among blacks: Increases malaria resistance
Heinz bodies, oxidized Hemoglobin precipitates in RBCs
Bite cells, phagocytic removal of heinz bodies by splenic macrophages leaves cells bitten shaped

172
Q

Essential Fructosuria

A

defect in fructokinase (makes fructose into fructose-1-p)
autosomal recessive
asymptomatic condition, fructose NOT trapped in cells
fructose high in urine

173
Q

Fructose Intolerance

A

Defect in Aldolase B
Autosomal Recessive
Fructose-1-P builds up in cells, decreases Phosphate levels, inhibiting glycogenolysis and gluconeogenesis
Urine has glucose and reducing sugar in it
Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
Treatment: Avoid fructose and Sucrose (glucose+fructose)

FAB GUT
fructose intolerance is Aldolase B
galactose intolerance is urydyltransferse

174
Q

Galactokinase Deficiency

A

deficiency of galactokinase
Autosomal Recessive
Galactitol builds up if galactose is in diet
galactose appears in blood and urine, infantile cataracts–> baby fails to track objects or develop a social smile

175
Q

Classic galactosemia

A

No galactose-1-phosphate uridyltransferase
Autosomal recessive
damage is caused by accumulation of toxic stuff (galactitol in the lense of eye)
Symptoms: FTT, Jaundice, hepatomegaly, infantile cataracts, intellectual disability
Treat: exclude galactose and lactose (galactose+glucose) from diet

FAB GUT
fructose intolerance is Aldolase B
galactose intolerance is urydyltransferse

176
Q

Sorbitol

A

Alcohol counterpart to glucose
traps glucose in cell
Glucose into Sorbitol via aldose reductase
Sorbitol into Fructose via sorbitol dehydrogenase

177
Q

decreased Sorbitol dehydrogenase amounts

A

Build up of sorbitol in cells
causes osmotic damage
cataracts, retinopathy, peripheral neuropathy as seen with chronic hyperglycemia in diabetics

178
Q

Lactase deficiency: Insufficient Lactase Enzyme

A

Dietary Lactose intolerance. Lactase functions on the brush border to digest lactose into glucose and galactose

179
Q

Lactase Deficiency: Primary

A

Age-dependent decline after childhood (absence of lactase-persistent allele), common in people of asian, african and native american descent

180
Q

Lactase Deficiency: Secondary

A

Loss of brush border due to gastroenteritis

181
Q

Congenital lactase Deficiency

A

rare, due to defective gene
Stool demonstrates low pH and breath shows increased hydrogen content with lactose tolerance test. Intestinal biopsy shows normal mucosa in patients with hereditary lactose intolerance

182
Q

Hyperammonemia

A

Can be aquaried (liver disease) or hereditary (urea cycle enzyme deficiency)
Results in excess in NH4 which depletes alpha-ketoglutarate, leading to inhibition of the TCA
Treatment: limit protein in diet, Benzoate or phenylbutyrate bind amino acids and let you excrete them.

183
Q

Ammonia Intoxication

A

Tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision.

184
Q

N-acetylglutamate

A

required cofactor for carbamoyl phosphate synthase I
Absence of N-acetylglutamate leads to hyperammonemia
Presentation is identical to carbamoyl phosphate synthetase I deficiency.
Increase ornithine with normal urea cycle ezymes suggests hereditary N-acetylglutamate deficiency

185
Q

Ornithine transcarbamylase deficiency

A

most common urea cycle disorder
X-linked recessive (all other urea cycle enzyme deficiencies are autosomal recessive)
interferes with body’s ability to eliminate ammonia
often evident in first days of life
excess cabamoyl phosphate is converted to orotic acid
increased orotic acid in blood, decreased BUN, symptoms of hyperammonemia

186
Q

Phenylketonuria

A

Autosomal recessive
Due to decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor
Avoid asparatame (n-aspartyl-phenylalanine methyl ester)
Tyrosine becomes essential
Increased phenylalanine leads to excess phenylketones
Disorder of aromatic amino acid metabolism leads to musty body odor

187
Q

Alkaptonuria

A

congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate
autosomal recessive: benign disease
Findings: dark connective tissue, brown pigmented selerae, urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage)

al capone is a tyrant and a homo homo but he is also a gent

188
Q

Homocystinuria

A

Types (all autosomal recessive)
all forms reult in excess homocysteine
Findings: increased homocysteine in urine, intellectual disability, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), thrombosis, and atherosclerosis (MI and Strokes)

189
Q

Cystinuria

A

hereditary defect of renal PCT and intestinal amino acid transporter for Cysteine, Ornithine, Lysine, and arginine (COLA)
Excess cystine in the urine can lead to precipitation of hexagonal yellow-brown cystine stones. Forms radio opaque crystals
nitroprusside cyanide test is diagnostic should be positive/purple
Autosomal recessive
treatment urinary alkalization and chelating agents, increased hydration

190
Q

Von Gierke Disease (Type 1)

A

Glycogen storage disease
Glucose-6-phosphatASE deficiency (not to be confused with glucose-6 phosphate dehydrogenase deficiency)
Autosomal recessive
Severe fast hypoglycemia
Increased glycogen in liver, increase blood lactate, hepatomegaly
Treatment: frequent oral glucose, avoid fructose/galactose

your liver can break up glycogen, but cannot dephosphorylate glucose, so the glucose is trapped in the cells

191
Q

Pompe Disease (Type II)

A
Glycogen storage disease
Lysosomal alpha1,4-glucosidase deficient
Autosomal recessive
Cardiomyopathy and systemic fining leading to early death
(Pompe trashes the Pump)

large tounge, hepatomegaly

192
Q

Cori Disease (Type III)

A

Glycogen storage disease
Debraching enzyme (alpha-1,6-glucosidase) deficient
Autosomal recessive
milder form of type 1 with normal blood lactate levels
Gluconeogenesis still intact

193
Q

McArdle Disease (Type V)

A

Glycogen storage disease
Skeletal muscle glycogen phosphorylase deficient (myophoshporylase)
Autosomal recessive
Increased glycogen in muscle, muscle cramps with strenuous excecise (patient will complain of sprinting, but walking is fine), myoglobinurea with exercise, arrhythmia, electrolyte abnormalities

Removes 1,4-glucosyl residues from the glycogen, freeing glucose-1-phosphate, which occurs in the cytosol

194
Q

Type IV (Anderson) Glycogen storage disease

A
Glycogen storage disease
no branching enzyme
You die
remember ABCD
Anderson - Branching
Cori - Debranching
195
Q

Fabry Disease

A
Lysosomal Storage Disease
Peripheral neuropathy of hands and feet (patients feel their extremities burning), angiokeratomas, cardiomyopathy
deficient alpha-galactosidase A
Ceramide trihexoside build up
X linked recessive
196
Q

Gaucher disease

A

Most common Lysosomal Storage Disease
Hepatosplenomegaly, pacytopenia, aseptic necrosis of femir, bone crises, gaucher cells (lipid laden macrophages that look like crushed tissue paper),
treatment is recombinant glucocerebrosidase
Deficient glucocerebrosidase
build up of glucocerebroside
Autosomal Recessive

gaucher - glucocerebrosidase
Krabbe - galactocerebrosidase

197
Q

Niemann-Pick Disease

A
Lysosomal Storage Disease
Sphingomyelinase deficient
Sphingomyelin builds up
Autosomal recessive
Progressive neurodegeneration, cherry red spot on eyes, foam cells, hepatosplenomegaly (Tay-sachs has no hepatosplenomegaly)
No man picks (Niemann-Pick) his nose with
his sphinger (sphingomyelinase)

ashkenazi jews

198
Q

Tay-Sachs Disease

A
Lysosomal Storage Disease
Progressive neurodegeneration, cherry red spots, lysosomes with onion skin, NO hepatosplenomegaly
Hexosaminidase A deficient
build up of GM2 ganglioside
Autosomal recessive
Frameshift mutation
Tay-SaX lacks heXosaminidase.

ashkenazi jews

199
Q

Krabbe Disease

A

Lysosomal Storage Disease
Peripheral neuropathy, developmental delay, optic atrophy globoid cells - remember the globe krabby patty thing? best burgers on the GLOBE and in the GALAXY (galacto…)
Deficient Glactocereborsidase
Galactocerebroside and psychosine builds up (its a psycho scene at the krusty krabbe)
Autosomal recessive

200
Q

Metachromic Leukodystrophy

A
Lysosomal Storage Disease
Central and peripheral demyelination with ataxia, demetia
deficient arylsulfatase A
Cerebroside sulfate builds up
Autosomal recessive

the metachromic colored ARYans are you CEREbral Bros

201
Q

Hurler Syndrome

A

Lysosomal Storage Disease
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
deficient alpha-L-iduronidase
build up of heparan sulfate and dermatan sulfate
Autosomal recessive

“Hurler” is a funny way to say Hailey
Hailey is married to Ron swanson the ALPHA male because she said “I Do, Ron” (iduronase). And ron has bad eating habits so he needs a build up of heparin (buildup of heparan sulfate)

lmao

202
Q

Hunter Syndrome

A

Lysosomal Storage Disease
mulder Hurler + aggressive behavior, no corneal clouding
Deficient Iduronate sulfatase
Build up of heparan sulfate, dermatan sulfate
X Linked recessive

Hunters need to be able to see (like hurler, but no corneal clouding) so they can hit their target (X-linked recessive)

203
Q

Carnitine Deficiency

A

inability to transport LCFAs into the mitochondria, resulting in toxic accumulation.
Weakness, hypotonia, hypoketotic hypoglycemia

204
Q

Acyl-CoA dehydrogenase deficiency

A

increased dicarboxylic acid, decrease glucose and ketonse
Acetyl-CoA is a + allosteric regulator of pyruvate carboxylase in glyconeogenesis
decrease acetyl-CoA leads to decrease fasting glucose
Autosomal recessive

205
Q

Ketone Bodies

A

Fatty acids and amino acids in liver are converted to acetoacetate ad beta-hydroxybutyrate (to be used in muscle and brain)
Breath smells like acetone
urine test for ketones does not detect beta-hydroxybutyrate

206
Q

Maple Syrup Urine Disease

A

Autosomal recessive
Blocked degradation of branched amino acids (isoleucine, leucine, valine)
decreased alpha-ketoacid dehydrogenase cause increased alpha-ketoacids in blood
causes severe CNS defect

207
Q

Fed State (after a meal): where is energy coming from

A

Glycolysis and aerobic respiration

insulin stimulates storage of lipids, proteins, and glycogen

208
Q

Fasting (between meals): where is energy coming from

A

Hepatic glycogenolysis
adipose release of FFA (minor)
Glucagon, adrenaline stimulate use of fuel reserves

209
Q

Starvation days 1-3: where is energy coming from

A

Blood glucose levels are maintained: glycogenolysis, adipose release of FFA
Glycogen reserves depleted after 1 day, RBCs lack mitochondria and so cannot use ketones

210
Q

Starvation days 3+:where is energy coming from

A

adipose stores, brain uses ketones mainly, after these are depleted vital protein degradation accelerates leading to organ failure and death
Amount of excess stores determines survival time

211
Q

Apolipoprotein E

A

Mediates remnant uptake

works with all cholesterol molecules except LDL

212
Q

Apolipoprotein A-I

A

Activates LCAT

works with chylomicrons and HDL

213
Q

Apolipoprotein C-II

A

Lipoprotein Lipase cofactor (activates LPL)

works with Chylomicron, VLDL, HDL

214
Q

Apolipoprotein B-48

A

Mediates chylomicron secretion

Works with chylomicrons, chylomicron reminants

215
Q

Apolipoprotein B-100

A

Binds LDL receptor

Works with VLDL, IDL, LDL

216
Q

Lipoprotein lipase

A

degradation of TG circulating in chylomicrons and VLDLs. found on vascular endothelial surface

217
Q

Chylomicrons

A

Delivers dietary TGs to peripheral tissue
delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their triacylglycerols
secreted by intestinal epithelial cells

218
Q

VLDL

A

delivers hepatic TGs to peripheral tissue

secreted by liver

219
Q

IDL

A

formed in the degradation of VLDL

delivers TGs and cholesterol to liver

220
Q

LDL

A

delivers hepatic cholesterol to peripheral tissues
formed by hepatic lipase modifications of IDL in the peripheral tissue
taken up by target cells via receptor-mediated endocytosis

221
Q

HDL

A

mediates reverse cholesterol transport from periphery to liver
acts as a repository for apoC and apoE which are needed for chylomicron and VLDL metabolism
secreted from both liver and intestine
alcohol increases synthesis

222
Q

Type 1 hyperchylomicronemia

A

increased blood levels of chylomicrons, TG, cholesterol
Autosomal recessive
lipoprotein lipase deficiency or altered apoprotein C-II
causes pancreatitis, hepatosplenomegaly, eruptive pruritic xanthomas with no increase for atherosclerosis

223
Q

Type IIa familial hypercholesterolemia

A
LDL cholesterol are increased in blood
Autosomal dominant 
absent or defective LDL receptors
Heterozygotes around 300mg/dl
Homozygotes around 700mg/dl
causes accelerated atherosclerosis
MI before 20 can happen
achilles xanthomas 
corneal arcus
224
Q

Type IV- Hypertriglyceridemia

A

VLDL and TG increased in blood
Autosomal dominant
Hepatic overproduction of VLDL, causes pancreatitis

225
Q

nonpolyposis colorectal cancer

what is going wrong with DNA

A

mismatch repair,

newly synthesized strand is recognized, mismatched nucleotides are removed, and the gap is filled in normal people

226
Q

patient with coarse facial features, clouded corneas, restricted joint movement

A

I-cell disease

failure of golgi to phosphorylate mannose residues onto glycoproteins (which is normally used to take them to the lysosome)

227
Q

6-month boy

small, vomits with bottled milk, jaundice, bilateral clouding of lenses, hepatomegaly, developmental delay

A

Classic galactosemia
autosomal recessive
galactose-1-phosphate uridyltransferase deficient

cannot convert galactose into glucose

Galactol does damage to eyes

galactokinase deficiency would be less severe with mostly corneal clouding

228
Q

fatty liver in alcoholics is due to an increased ratio of what electron transporting molecule

A

increase in the NADH:NAD ratio when ethanol gets converted to acetaldehyde in the cytosol

229
Q

Patient has normal female development but doesn’t have menarche

elevated testosterone and estrogen

A

androgen insensitivity

she’s a guy

there’s a whole house episode of it

230
Q

what amino acids are required in the diet during periods of growth

A

Arg and His

231
Q

infant with FTT, hypoglycemia, hepatomegaly

A
Von Gierke (type I) glycogen storage disease
Cori disease (type III) glycogen storage disease
232
Q

mneumonic for the glycogen storage diseases

A

Very Poor Carbohydrate Metabolism

Von Gierke - hypoglycemia, increased blood lactate, hepatomegaly
Pompe - heart problems, enlarged tongue, hepatomegaly
Cori - milder von girke, normal blood lactate
McArdle - painful cramps, myoglobinuria with sprinting, arrhythmia

I - Glucose-1-phosphatase
II - lysosomal alpha-1.4-glucosidase (acid maltase)
III - Debranching enzyme (alpha-1,6-glucosidase)
V - Skeletal muscle glycogen phosphorylase

IV is incompatible with life

233
Q

intellectual disability, marfanoid habitus, lens subluxation

comes in with MI

what disease

A

Homocystinuria - excess homocysteine in urine, intellectual disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation, thrombosis, atherosclerosis

3 types, all autosomal recessive:

  • cystathioneine synthase deficiency. homocystine -X-> cystathionine –> cysteine
    (Tx: decrease methionine, increase cysteine, increase b12 and folate)
  • homocysteine methyltransferase deficiency. Homocysteine -X-> methionine (Tx is increase methionine)
  • decreased affinity of cystathionine synthase for pyridoxal phosphate (give a shit ton of B6 and cystine)
234
Q

female who comes in at around age 12 with enlarging clitoris

A

5alpha reductase deficiency - inability to convert
testosterone into DHT; male internal
genitalia, ambiguous external genitalia until
puberty (when increases in testosterone levels cause
masculinization)

235
Q

increasing the michaelis-menten constant of an enzyme means what

A

something is competitively inhibiting it

236
Q

niacin is derived from what amino acid

A

tryptophan

(can see pellagra in hartnup disease, which is characterized by a lack of tryptophan absorption)

(also can see pellagra in malignant carcinoid syndrome because of an increase in tryptophan metabolism)

237
Q

loss of a tumor suppressor gene on chromosome 17

what disease

A

Li-Fraumeni syndrome - autosomal dominant disorder that causes cancers before the age of 45.

the gene is p53 and can lead to MANY different cancers

238
Q

alcoholic with angiomas, confusion, slurring, and asterixis

what is going on
what do you give

A

hepatic encephalopathy due to buildup of ammonia.

can be treated with lactulose to generate NH4, low protein diet, and rifaximin (kills intestinal bacteria)

239
Q

where is the first place in the body that urea is metabolized

A

converted to carbamoyl phosphate (by carbamoyl phosphatase with cofactor N-acetylglutamate) in the mitochondria!

240
Q

Mnemonic for Autosomal Dominant diseases. Think Dominant

A

Hunting MEN FAP thier Tubes and Shperes in Hip Cafés and get Tele Chols from Li about Marfans.

Huntingtons
Multiple Endocrine Neoplasia 
Tuberous Sclerosis 
Hereditary Sphereocytosis
von Hippel-Lindau
Cafe = Neurofibromatosis type 1 (NF2 is also dominant but doesn't have cafe au lait spots)
familial hyperCHOLesterolemia
Li-Fraumeni
Marfans
241
Q

lipoprotein lipase cofactor

A

ApoC-II

242
Q

Mnemonic for X linked recessive.

A

a Fable about a Dutch Hunter with White eyes and Wiskers, wearing a Burton coat. He bites his hands and bleeds so he gets an OTC (over the counter) medication called G6
Fabry’s Disease
Deuchenne’s Muscular dystrophy (and Becker’s)
Ocular Albinism
Wiskott-Aldrich syndrome
Bruton’s Agammaglobulinemia
bite hands = Lesch Nyhan
Bleeding = Hemophilia
OTC = Ornitine Transcarbamylase deficiency
G6PD

243
Q

patient comes in with pellagra like symptoms and neutral aminoaciduria

A

hartnup disease, inherited mutations in the B(not) transporter

failure to absorb tryptophan

(tryptophan is used to synthesize niacin)

244
Q

lipoprotein lipase cofactor

A

ApoC-II

245
Q

increased serum homocystine and methylmalonic acid levels

A

vit b12 deficiency

B12 is a cofactor for homocysteine methyltransferase
(transfers CH3 groups as methylcobalamin)
and methylmalonyl-CoA mutase.

246
Q

Normal CD19+ B cell count,
decreased pro-B, decreased Ιg of all classes.
Absent/scanty lymph nodes and
tonsils.

A

X linked (bruton) agammaglobulinemia

Defect in BTK, a tyrosine
kinase gene p no B cell
maturation. X-linked recessive
(mostly in Boys).

247
Q

x and y intercept of line-weaver burk plots

A

Y - intercept = 1/Vmax

(the y intercept goes up; Vmax goes down)

X- intercept = -1/Km

(slope goes up, Km goes down)

248
Q

patient presents with cancer at a young age, and there are other people in her family with cancer diagnoses at young ages

cancers are breast, ovarian, and osteosarcoma, adrenocortical tumors

what syndrome?
what gene?

A

Li-Fraumeni syndrome (autosomal dominant)

mutation in p53

249
Q

What is happening is someone on nitroprusside if they get confused and their lips turn pink

A

cyanide poisoning

inhibits cytochrome oxidase

250
Q

you give a cephalosporin to an infant and see a bunch of bruising

what enzyme is affected

A

caboxylation of glutamic acid residues (gamma carboxylation of factors II, VII, IX, X) is decreased because they have a vit K deficiency (because their gut flora were killed

251
Q

which of the sphingolipidoses causes demyelination with ataxia early in life

A

metachromic leukodystrophy

defect in arylsulfatase A

build up of cerebroside sulfate

252
Q

small red papules on abdomen and scrotum, hyperkeratosis, paresthesias in the digits bilaterally and heat intolerance

A

Fabrys

X-linked recessive

build up of ceramide trihexoside

defect in alpha-galactosidase A

253
Q

microcytic anemia with basophilic stippling, fatigue, myalgias, poor concentration, worked in a factory

what is going on
what metabolite is likely elevated in the urine

A

lead poisoning

delta-aminolevulinic acid

254
Q

Familial hypocalciuric hypercalcemia

A

increased serum calcium, decreased calcium urine, increased PTH all due to a mutation in the calcium sensing receptor which is made from the calcium sensing receptor gene on chromosome 3q

255
Q

Amyloidosis: where is the amyloid made that is getting deposited everywhere

A

The liver makes serum associated amyloid protein, which goes to the other organs and makes amyloid associated protein.

256
Q

Needlestick injury: what chronic diseases are you likely to get

A

Hep C and Hep B > HIV (Unless you know the diseases of the patient, but if unknown it goes by epidemiology)

257
Q

Pyruvate decarboxylase deficiency

A

Leads to build up of pyruvate, alanine, and lactate; also see increased ketoacids due to lack of energy; autosomal recessive; shows up early in life with seizures.