Biochem-First Aid 2007

Front 1

fat-soluble vitamins
-desc
-how absorbed
-what causes malabsorption

Back 1

Vit "ADEK"

-higher risk for toxicity than water-soluble vitamins b/c these are stored in fat
-absorbed from gut in term ileum
==>thus, ppl at risk for deficiencies of fat-soluble vitamins are ppl who malasorb fat:
-CF
-celiac sprue
-ingesting mineral oil

Front 2

water-soluble vitamins

Back 2

Goljan: water-soluble vitamins are co-factors for biochemical rxns

(cofactor) for rxns involving this ==>enzyme

B1(=thiamine) ==>FFP
B2(=riboflavin) ==>FAD, FMN
B3(=niacin) ==>NAD+
B5(=penthothenate)==>CoA
B6(=pyridoxine) ==>PP
B12(=cobalamin)
C (ascrobic acid)
Biotin
Folate

Front 3

other names for Vit B6

Back 3

pyridoxine
pyridoxal
pyridoxamine

Front 4

dermatitis, diarrhea, and glossitis

Back 4

Vit B deficiencies

Front 5

dermatitis, diarrhea, & dementia

Back 5

Vit B3 (niacin) deficiency

Front 6

Vit A
-deficiency
-fxn
-xs

Back 6

Vit A=retinol ("retinol"==>sounds like retina==>eye)

*deficiency=night blindness
*fxn=component of visual pigments (retina)
*xs=arthralgias, skin changes, fatigue, H/A, alopecia, sore throat

Front 7

Vit B1
-deficiency
-fxn

Back 7

Vit B1=thiamine

-deficiency:
1. BeriBeri (mneum: "Ber1-Ber1")

a. dry beriberi- polyneuritis, muscle wasting

b. wet beriberi-heart failure (dilated cardiomyopathy b/c not enough ATP)==>edema ("wet" b/c edema=fluid)

2. Wernicke-Korsakoff

*Wernicke encephalopathy
--confusion
--ataxia
--nystagmus
[all signs of being drunk]

*Korsakoff psychosis
-lack of memory ("blackouts" from being drunk)

-Fxn of thiamine:
*co-factor for:
-[Goljan] dehydrogenase rxns, i.e. pyruvate dehydrogenase, which convers pyruvate==>Acetyl CoA==>TCA cycle (ATP!!)
*thus, if no thiamine, major ATP depletion
==>mental status abnl
==>cardiac myopathy (both ventricles enlarged b/c heart must work harder)

[First Aid: "cofactor for oxidative decarboxylation of alpha-keto-acidds (pyruvate, alpha-ketoglutarate]

2. transketolase in HMP shunt

Front 8

Vit B2
-deficiency
-fxn

Back 8

Vit B2=Riboflavin

-Deficiency:
*angular stomatitis/cheilosis
(irritation and fissuring in corners of lips)
*corneal vascularization

-Fxn: cofactor in redox rxns (FADH2, FMN)

Front 9

Vit B3

Back 9

=niacin

Fxn:
-redox rxns (NAD, NADP) (mneum: "N"AD derived from "N"iacin)
-Niacin derived from Trp using Vit B6

Deficiency of niacin(="Pellagra") d/t:
-Hartnup dz (decr Trp absorption)
-Carcinoid synrome (incr Trp metabolism)
-INH (decr Vit B6)

Sx of Pellagra ("3 D's"):
Dementia
Dermatitis
Diarrhea

Front 10

MC vit deficiency in US?

Back 10

folate deficiency (b/c americans don't eat enough veggies)

Front 11

ethanol metabolism

Back 11

1. alcohol dehydrogenase converts alcohol==>acetaldehyde

2. acetaldehyde dehydrogenase converts acetaldehyde==>acetate

-alcohol dehydrogenase operates via zero-order kinetics
-Disulfiram ("Antabuse") inhibits acetaldehyde dehydrogenase==>acetaldehyde accumulates==>worsens the hangover!

Front 12

ethanol hypoglycemia

Back 12

ethanol metabolism incr NADH/NAD+ ratio in liver
==>diverts pyruvate to lactate & OAA to malate
==>shunts away from gluconeogenesis (==>hypoglcycemia) & toward fatty acid synthesis (==>hepatic fatty change="hepoatocellular steatosis")

Front 13

kwashiorkor vs. marasmus

Back 13

kwashiokor=
PROTEIN deficiency
==>cannot put proteins around VLDL (cannot form lipoprotein)
==>liver cannot ship out VLDL's (fats)
==>huge fatty liver==>swollen belly

Also, liver prob==>cannot make albumin==>edema

----------------------------
Marasmus=energy (calorie) deficiency
==>lose sub-Q fat
==>tissue and muscle wasting

Front 14

chromatin structure

Back 14

"beads on a string" (beads=(+) histone, string= (-)DNA)

*(-) DNA loops twice around each nucleosome core (2 each of H2A, H2B, H3, and H4)

*H1 holds ties nucleosomes together in a string (30-nm fiber)

Front 15

heterochromatin

Back 15

-condensed
-transcriptionally inactive

Front 16

euchromatin

Back 16

-not condensed
-transcriptionally active

Front 17

transition

Back 17

substituting purine for purine or pyrimidine for pyrimidine

mneum: transItion=Identical type

Front 18

transversion

Back 18

substituting purine for pyrimidine or vice versa

mneum: transVersion=conVersion b/w types

Front 19

what does this mean:

"The genetic code is unambiguous."

Back 19

each codon specifies only 1 aa

Front 20

what does this mean:

"The genetic code is commaless."

Back 20

start from fixed point and read bases continuously

Front 21

What does this mean:

"the genetic code is non-overlapping."

Back 21

Read from fixed starting point as a continuous sequence of bases.

Front 22

What does this mean:

"the genetic code is redudant."

Back 22

more than one codon can code for the same aa.

Front 23

What does this mean:

"the genetic code is degenerate.

Back 23

more than one codon can code for the same aa.

Front 24

replication in eukaryotes vs. prokaryotes

Back 24

Eurkaryotes:
*multiple origins of rep
*rep begins in A-T rich region (TATA box)

Prokaryotes:
*single origin of repliation (goes in a circle)
*continuous bidirectional DNA synthesis on leading strand and discontinuous (Okazaki fragments) on lagging strand

Front 25

DNA topoisomerases

Back 25

creates nick in helix to relieve supercoils (AKA unknot the DNA)
==>then helicase can unwind the 2 strands so DNA can be replicated/transcribed

Front 26

primase

Back 26

makes RNA primer, on which DNA polymerase III can initiate replication

Front 27

DNA polymerase III

Back 27

*elongates chain in 5'==>3' direction (adds deoxynucleotides to 3' end til it reaches primer of the preceding segment)

*exonuclease proofreads in 3==>5' direction

Front 28

DNA polymerase I

Back 28

excises RNA primer w/5'-->3' exonuclease and replaces w/DNA

Front 29

DNA ligase

Back 29

seals

Front 30

nucleotide excision repair

Back 30

-specific endonucleases remove and replace short section of DNA around the damage (e.g. pyrimidine dimers, methylated bases, chemical adducts formed by carcinogens and chemotherapeutic drugs)
-DNA poly and ligase fill and reseal the gap, respectively

*this is mutated in xeroderma pigmentosa (dry skin w/melanoma and other cancers)

Front 31

xeroderma pigmentosa

Back 31

(dry skin assoc w/melanoma and other cancers)

defective nucleotide excision repair

Front 32

base excision repair

Back 32

1. specific glycosylases recognize and remove damaged bases (e.g. U, hypoxanthine and xanthine from deamination, and oxidized bases)

2. AP endonuclease cuts DNA at apyrimidine site

3. empty sugar removed

4. gap filled and resealed

Front 33

mismatch repair

Back 33

1. unmethylated, newly synthesized string is recognized

2. mismatched nucleotides removed

3. gap filled and resealed

*this process is defective in HNPCC (Hereditary Non-Polyposis Colon Cancer)

Front 34

nonhomologous end joining

Back 34

just like it sounds: non-homologous ends of 2 DNA fragments are brought together

Front 35

Synthesis direction of DNA/RNA/protein

Back 35

DNA, RNA, and protein are all synthesizedin 5'--->3' direction

5' of incoming nucleotide bears ATP (E for bond)

3' of nascent (growing) chain is the target)

Front 36

how are aa's linked?

Back 36

N to C

Front 37

types of RNA

Back 37

mRNA=largest (mRNA= "m"assive)
tRNA=smallest(tRNA= "t"iny)
rRNA=most abundant (rRNA= "r"ampant")

Front 38

RNA polymerases

Back 38

EUKARYOTES:

RNA polymerase I makes rRNA
RNA polymerase II makes mRNA
RNA polymerase III mkaes tRNA

(note: I, II, and III are numbered as their products are used in protein synthesis)


PROKARYOTES:
RNA polymerase (multisubunit complex) makes all 3 kinds of RNA

Front 39

mRNA initiation codon

Back 39

EUKARYOTES:
-codes for AUG=Methionine
-maybe removed before translation completed

PROKARYOTES:
-codes for formyl-methionine (f-Met)

mneum: "AUG inAUGurates protein synthesis"

Front 40

mRNA stop codons

Back 40

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

Front 41

promoter

Back 41

site where RNA poly and other TF's bind to DNA upstream from gene locus (AT-rich upstream sequence with TATA and CAAT boxes)

Front 42

enhancer

Back 42

*stretch of DNA where TF's bind==>regulate gene expression

*can be located close to, far from, or even within (in an intron) the gene it regulates

Front 43

operator

Back 43

site where negative regulators (repressors) bind

Front 44

splicing of mRNA

Back 44

1. primary transcript combines w/snRNP's to form spliceosome

2. Generate intermediate lariat structure (composed of introns)

3. Lariat released to remove intron precisely & join 2 exons

Front 45

RNA processing

Back 45

*occurs in EUKARYOTES

intial transcript=hnRNA (heterogenous nuclear RNA)

then:
1. 5' cap (7-methyl-G)
2. 3' tail (~200 A's)
3. splicing

==>now it's called "mRNA"

Front 46

tRNA
-structure

Back 46

all tRNA's (euk and prok) have CCA at 3' end

Front 47

what ensures accuracy of aa selection?

Back 47

1. aminoacyl tRNA synthetase (scrutinizes aa before and after it binds tRNA; if incorrect, it hydrolyzes bond b/w tRNA & aa)

2. bonding of charged tRNA (=anticodon) to codon

Front 48

tRNA wobble

Back 48

accurate base pairing depends only on 1st two bases of codon;
-thus different bases in the 3rd "wobble" position may code for same tRNA/aa

Front 49

protein synthesis

Back 49

NOT FINISHED:

*Initiation:
Initiation factors help assemble the 30S ribosomal subunit w/initiator tRNA, released when mRNA and ribosomal subunit assemble w/the complex



-"A"TP= tRNA "A"ctivation (charging)
-"G"TP=tRNA "G"ripping and "G"oing places (translocation)
-"A" site=incoming "A"minoacyl tRNA
-"P" site=accomodates growing "P"eptide
-"E" site=holds "E"mpty tRNA as it exists

Front 50

Heinz bodies

Back 50

G6PD deficiency

(Heinz bodies=altered Hg precipitates within RBC's)

Front 51

inheritance pattern of G6PD deficiency

Back 51

X rec

Front 52

who gets G6PD deficiency?

Back 52

-boys (X-rec)
-AfAm

Front 53

HMP shunt

Back 53

=Pentose Phosphate Pathway

Purpose=Generate NADPH, which is req for:
--FA & steroid syn
--keeping glutathione (inside RBC's) in its reduced form (neutralize free radicals to prevent hemolytic anemia)
--CYP450

*all rxns occur in cytoplasm
*no ATP used or produced
*occur in
--lactating mammary glands
--liver
--adrenal corex
(=places for fatty acid or steroid synthesis)

Enzymes:
1. Oxidative (irreversible)=G6PD (*rate-limiting enzyme in HMP shunt)
==>produces NADPH

2. Nonoxidative (reversible)=
Transketolase (*req thiamine);
-produces:
~Ribose-5-P (nucleotide syn)
~G3P, F6P (glycolytic intermediates)

Front 54

G6PD deficiency

Back 54

G6PD is rate-limiting enzyme in HMP shunt (PPP), which produces NADPH, which is req to keep glutathione in its reduced form (in order to neutralize free radicals and oxidizing agents like:
--H2O2
--fava beans
--primaquine
--sulfonamides
--anti-TB drugs

Front 55

fructose intolerance

Back 55

-deficiency of Aldolase B (converts F1P==>DHAP & Glyceraldehyde)
==>buildup of F1P
==>less free phosphate
==>inhibits glyceogenolysis and gluconeogenesis

Front 56

essential fructosuria

Back 56

-deficiency of Fructokinase

*benign, no Sx

Front 57

Galactosemia

Back 57

*deficiency of Uridyl transferase (converts Galactose-1-P==>Glucose-1-P)
==>incr Galactitol (toxic)

Sx:
MR,
cataracts,
hepatosplenomegaly

Front 58

Galactokinase deficiency

Back 58

[Galactokinase converts Galactose==>Galactose-1-P]

deficiency==>
-galactosemia
-galactosuria
-Galactitol (toxic)

Front 59

et of lactase deficiency

Back 59

loss of lactose (brush border enzyme)

Front 60

aa: ketogenic only

Back 60

Leu, Lys

Front 61

aa: gluconeogenic only

Back 61

Val, Thr, Met, His, Arg

Front 62

aa: glucogenic/ketogenic

Back 62

Phe, Trp, Ile

Front 63

which aa are req during periods of growth?

Back 63

Arg & His (goljan: body builders take these)

Front 64

acidic aa?

Back 64

[acidic=negative at body pH)

Glu, Asp

mneum: "This Glu ("glue"=drug slang name for the drug "acid") takes like Asp ("ass")"

Front 65

basic aa

Back 65

Arg > Lys > His

(His has no charge at body pH)

Front 66

histones have lots of which aa?

Back 66

Arg & Lys

(these are basic aa [positive charge] and histones must be positive in order to bind (-) DNA in beads-on-a-string formation]

Front 67

hyperammonemia

Back 67

can be heredtiary (lack enzyme for urea cycle) or acquired (liver dz [urea cycle occurs in liver])

-incr NH3 uses up alpha-ketoglutarate
==>not enough alpha-ketoglutarate to run TCA cycle

Tx: Arginine (part of urea cycle)

Sx of ammonia intoxication:
-cerebral edema
-tremor
-vomiting
-slurred speech
-blurred vision

(looks like you're drunk)

Front 68

what does melanin derive from?

Back 68

phenylalanine==>tyrosine==>
DOPA (not dopamine)==>melanin

Front 69

what does thyroxine derive from?

Back 69

phenylalanine==>tyrosine

Front 70

what does dopamine derive from

Back 70

phenylalanine==>tyrosine

Front 71

what does NE derive from

Back 71

phenylalanine==>tyrosine

Front 72

what does Epi derive from

Back 72

phenylalanine==>tyrosine

Front 73

what does niacin derice from

Back 73

Trp

Front 74

what does serotonin derive from

Back 74

Trp

Front 75

what does heme dervice from

Back 75

glycine==>porphyrin==>heme

Front 76

what does porphyrin derive from

Back 76

glycine==>porphyrin==>heme

Front 77

what aa does creatine derive from

Back 77

arginine

makes sense; body builders take both Arg and creatine to bulk up

Front 78

what aa does urea derive from

Back 78

arginine

Front 79

what aa does NO derive from

Back 79

arginine

Front 80

what aa does GABA derive from

Back 80

glutamate==>GABA (*req B6 cofactor for glutamate decarboxylase)

Front 81

phenylketonuria

Back 81

*AR (auto rec) dz
*deficiency of phenylalanine hydroxylase (which converts phenylalanine==>tyrosine)
==>deficient tyrosine & phenylalanine builds up

Sx:
MR,
musty body odor,
eczema

Tx:
-incr tyrosine intake
-decr phenylalanine (aspartame)

Front 82

alkaptonuria

Back 82

AKA ochronosis

*deficient homogentisic acid oxidase (degrades tyrosine)

Sx: black urine, arthralgias
(benign dz)

Front 83

albinism

Back 83

*Congenital dz d/t failure of neural crest migration

*d/t deficiency of either:

1. tyrosinase (so cannot make melanin from tyrosine)

2. tyrosine transporters so cannot make melanin from tyrosine)

Results:
-skin cancer (d/t low melanin)

Front 84

homocysteinuria

Back 84

*see First Aid p. 103 for pathway w/enzymes:

homocysteine==>cystathione (via cystathione synthase, B6=cofactor)
==>cysteine

homocysteine==>methionine (via methionine synthase, B12=cofactor, which converts CH3-THF==>THF)

3 et (all AR) for homocysteinuria:

1. deficient cystathione synthase
==>Tx: decr homocysteine in diet, incr cysteine in diet

2. decr affinity of cystathione synthase for Vit B6
==>Tx: incr Vit B6 in diet

3. deficient methionine synthase

*no matter the cause, cysteine becomes essential aa (must eat it!)

Sx:
MR
osteoporosis
atherosclerosis (MI, stroke)
tallm (~Marfan's)
lens subluxation (downward and inward) (~Marfan's)

Front 85

cystinuria

Back 85

defective transporter for "COLA" (Cystine, Ornithine, Lysine, Arginine)
==>incr Cystine in urine
==>Cystine kidney stones

Tx: acetozolamide (alkanizes urine so you don't form stones)

Front 86

maple syrup dz

Back 86

-d/t deficient alpha-ketoacid dehydrogenase
-cannot metabolize branched chain aa (Isoleucine, Leucine, Valine; "I" "L"ove "V"ermont maple syrup)
==>incr alpha-ketoacids in blood, esp. leucine


Sx:
-MR, death within a year
-urine smells like maple syrup d/t keto-acids in urine (like how pts in DKA have sweet-smelling breathe)

Tx: decr consumption of Isoleucine, leucine, & valine

Front 87

protein synthesis

Back 87

1. Initiation:
-Initiation Factors bind 30S ribosome to tRNA

2. Elongation:
i. tRNA enters A site

ii. peptidotransferase moves tRNA from A to P site

iii. growing peptide "E"xits ribosome from "E" site

mneum:
-"A" site: incoming "A"minoacyl tRNA
-"P" site: for growing "P"eptide
-"E" site: protein "E"xists ribosome

* "A"TP=tRNA Activation (charging)
* "G"TP=tRNA "G"ripping & "G"oing places (translocation)


3. Termination: ribosome releases completed protein and then dissociates

Front 88

posttranslational modifications

Back 88

1. Trimming:
trim N or C group to convert zymogen==>active protein

2. Covalent alterations:
-Phosphorylation (add P)
-Glycosylation (add sugar)
-Hydroxylation (add OH)

3. Degradation:
tag protein with ubiquitin==>degradation

Front 89

permanent cells

Back 89

-remain in Go
-can only regenerate from stem cells

e.g.
-neurons
-SkM
-cardiac muscle
-RBC's

Front 90

stable cells

Back 90

-can go from Go==>G1 if stimulated

e.g. hepatocytes, leukocytes

Front 91

labile cells

Back 91

-never enter Go
-short G1
-divide rapidly

e.g.
BM
hair follicles
gut epithelium
skin

Front 92

RER

Back 92

site of:
*synthesis of proteins that will be exported/secreted

*addition of N-linked oligosaccharides to many proteins

-Nissl bodies (neurons)- synthesize enzymes (eg ChAT) & peptide neurotransmitters

-sites with lots RER:
*mucus-secreting goblet cells of sm int
*Ig-secreting plasma cells (b/c Ig=protein)

Front 93

SER

Back 93

site for:
-steroid synthesis ["S"ER for "S"teroid syntehsis)
-detox drugs and poisons

*sites w/lots SER:
-hepatocytes (do detox)
-steroid-producing cells of adrenal cortex

Front 94

Golgi

Back 94

*directs proteins from ER to
==>plasma memb
==>lysosomes
==>secretory vesicles

*adds mannose-6-P residues to lysosomal proteins to target them to lysosome

(failure of this==>I cell dz)

*adds N-oligosaccharide residue to asparagine

*adds O-oligosaccharide residue to serine & threonine

*assembles proteoglycans

*sulfation of sugars in proteoglycans & of selected tyrosine on proteins

Front 95

I cell dz

Back 95

failure of Golgi to add mannose-6-P residues to lysosomal proteins
==>lysosomal proteins not targeted to lysosome and are secreted outside the cell (bad!)

Sx:
*often fatal in childhood
-high plasma levels of lysosomal enzymes
-coarse facial features
-clouded corneas
-restricted joint mvmts

Front 96

vesicular trafficking proteins

Back 96

*COPI: retrograde; Golgi==>ER

*COPII: antegrade; ER==>golgi

*Clathrin (~"Katherine")
-receptor-mediated endocytosis
-carries products from lysosomes, plasma memb==>endosomes

Front 97

microtubules
-desc
-what drugs act on microtubules

Back 97

*purpose:
-form mitotic spindle
-form flagella, cilia (cilia has 9 + 2 arrangement of microtubules)



-cylindrical structure composed of 13 polymerized dimers of alpha and beta-tubulin arranged in a circle
-24 nm diameter

Drugs that act on microtubules
*Mebendazole/thiabendazole (anti-helminth)
*Griseofulvin (antifungal)
*Taxol (anti-breast cancer)
*Vincristine, vinblastine (anti-cancer)
*Colchicine (anti-gout)

Note: the last 3 Rx all are M-phase specific (anti-mitotic) that inhibit microtubule assembly.

Front 98

cilia

Back 98

9+2 arrangement of microtubules

(9 doublets of microtubules on periphery, 2 single microtubules in center)

Cilia moves via 2 motor units:
*Kinesin=anterograde mvmt
*Dynein=retrograde mvmt

-Dynein=
*ATPase that links peripheral 9 doublets
==>causes doublets to slide
==>bend cilium (cilia; dynein is part of the cilia)
==>allows retrograde mvmt

Defective cilia (d/t defective dynein arm)==>
*male/female infertility (sperm have no cilia)
*bronchiectasis
*recurrent sinusitis (no cilia in bronchioles to sweep away pathogens)

Front 99

Kartagener's syndrome

Back 99

*defective cilia d/t defective dynein arm

Results:
*male/female infertility (sperm have no cilia)
*recurrent sinusitis (no cilia in bronchioles to sweep away pathogens)
*bronchiectasis (=dilation of bronchi or bronchioles d/t constant inflammatory dz or obstruction)

Front 100

phosphatidylcholine

Back 100

AKA Lecithin

~Esterifies cholesterol (LCAT=Lecithin-Cholesterol Acetyltransferase)

~Major component of:
*RBC membranes
*bile
*surfactant (DPCC=DiPalmitoyl Phosphatidylcholine)

Front 101

Lecithin

Back 101

AKA Phosphatidylcholine

~Esterifies cholesterol
(LCAT=Lecithin-Cholesterol Acyltransferase)

~Major component of
*RBC membrane
*myelin
*bile
*surfactant (DPPC=DiPalmitoyl Phosphatidylcholine)

Front 102

what increases melting temperature of cells

Back 102

if plasma membrane has lots of cholesterol or long saturated fatty acid content

Front 103

Na-K ATPase
-desc
-what drugs affect

Back 103

-ATP site is on cytoplasmic (intracellular) side
==>phosphorylates the pump as Na leaves and K enters

Drugs that inhibit Na-K pump:
-ouabain: block K sit
-cardiac glycosides (digoxin, digitoxin): block ATPase==>cell depolarizes==>incr cardiac dp/dt

Front 104

Collagen

Back 104

Type 1=bONE ("1"="ONE")
Type 2=cartilage (carTWOlage)
Type 3=reticulin, located in:
-skin
-bv
-granulation tissue
-fetal tissue
-uterus

Type 4=BM ("4"=fall to the "floor" (BM))

Front 105

Ehler-Danlos syndrome

Back 105

faulty collagen synthesis==>

1. Hyperextensible skin
2. Hypermobile joints
3. Easy bruising (b/c Type 3 collagen is most often affected==>bv instability==>easy bruising)

Front 106

osteogenesis imperfecta

Back 106

*abnl collagen, usu Type 1 (bone)
*AD
*can be confused with child abuse

Sx:
1. multiple fractures (b/c abnl Type 1 collagen (bone))
2. blue sclera (no collagen)
3. hearing loss (abnl middle ear bones)
4. poor dentition (no collagen)

Front 107

vimentin stains what?

Back 107

connective tissue

Front 108

desmin stains what?

Back 108

muscle (mneum: muscular man named "Desmond")

Front 109

cytokeratin stains what?

Back 109

epithelium

Front 110

GFAP stains what?

Back 110

[GFAP=Glial fibrillary acid proteins]

neuroglia

Front 111

neurofilaments stain what?

Back 111

neurons

Front 112

elastin is rich in which aa's?

Back 112

proline and lysine

Front 113

Marfan's is a defect in what?

Back 113

fibrillin (major component of microfibrils, which form sheath around elastin of CT)

Front 114

antitrypsin

Back 114

-inhibits elastase
-emphysema: xs elastase (thus, chest expanded) b/c cigarettes destroy antitrypsin

Front 115

which metabolism rxns occur in mitochondria?

Back 115

Mitochondria only:
-AcCoA synthesis
-TCA
-Beta oxidation (fatty acid oxidation)

Both mito & cytosol:
-gluconeogenesis
-urea cycle
-heme synthesis

Front 116

which metabolism rxns occur in cytosol?

Back 116

-Glycolysis
-FA synthesis
-HMP shunt (PPP)
-protein synthesis (RER)
-steroid synthesis (SER)

Both mito & cytosol:
-gluconeogenesis
-urea cycle
-heme synthesis

Front 117

which metabolism rxns occur in boht mito & cytosol?

Back 117

-gluconeogenesis
-urea cycle
-heme synthesis

Front 118

how many ATP's produced in aerobic metabolism?

Back 118

-38 ATP via malate shuttle
-36 ATP via G3P shuttle

Front 119

respiratory burst

Back 119

oxygen (via NADPH oxidase)
==>superoxide (via superoxide dismutase)
==>H2O2
(via myeloperoxidase)==>HOCl=bleach
(via catalase/glutathione peroxidase: this converts reduced glutathione==>oxidized)
==>(via glutathione reductse) regenerate reduced gluthatione: this converts NADPH (from HMP shunt)==>NADP+
==>(via G6PD) regenerate NADPH

Front 120

cherry red spot on macula

Back 120

Tay Sachs,
Niemann Pick

(both assoc w/Ashkenazi Jews, Eastern Europeans)

Front 121

regulation of Glycogen synthase

Back 121

[fed state (+) Glycogen synthase]

Liver & SkM:
+Insulin
-Epi

Liver only:
+Glucose
-Glucagon

Front 122

regulation of Glycogen phosphorylase

Back 122

[Glycogen phosphorylase converts glycogen==>glucose;
thus, fasting state (+) Glycogen phosphorylase]

Liver & SkM:
+Epi
-Insulin

Liver only:
+Glucagon

Muscle only:
+AMP (sign of low Energy)
-ATP

Front 123

GLUT receptors

Back 123

GLUT 1:
RBC
Brain

GLUT2 (bidirectional):
B islet cells
liver
kidney

GLUT4 (insulin-responsive):
SkM
adipose

Front 124

what doesn't need insulin for glucose uptake

Back 124

"BRICK L:

Brain
RBC
Intestine
Cornea
Kidney
Lens

(the last 3 are complications of DM)

Front 125

glycogen
-where stored
-purpose

Back 125

Glycogen stored in:

1. SkM: quickly converts glycogen==>glucose to use during exercise

2. Liver: uses glycogen to maintain nl BG levels

Front 126

glycogen metabolism

Back 126

Forming glycogen:
1. G6P <==> G1P
2. G1P==>UDP-glucose (enzyme= Glycogen synthase)
3. Branching enzyme (forms glycogen's alpha-1,6 branches)

Lyse glycogen==>glucose:
1. Debranching enzyme (lyses glycogen's alpha-1,6 linkages)
2. Glycogen phosphorylase

Front 127

glycogen metabolism

Back 127

Forming glycogen:
1. G6P <==> G1P
2. G1P==>UDP-glucose (enzyme= Glycogen synthase)
3. Branching enzyme (forms glycogen's alpha-1,6 branches)

Lyse glycogen==>glucose:
1. Debranching enzyme (lyses glycogen's alpha-1,6 linkages)
2. Glycogen phosphorylase

Front 128

lysosomal storage dz with:

-peripheral neuropathy (hands/feet)
-CV dz
-renal dz
-angiokeratoma

*name of dz?
*inheritance pattern
*defective enzyme
*build-up of what?

Back 128

Fabry's

X-rec (ALL other lysosomal storage dz's are AR)

-defective enzyme=alpha-galactosidase

-build-up of Ceramide Trihexose

Front 129

lysosomal storage dz with:
-progressive neurodegeneration
-cherry red spot on macula
-lysozymes w/onion skin


*name of dz?
*inheritance pattern
*defective enzyme
*build-up of what?

Back 129

Tay-Sachs (Eastern Europeans)
*AR
*defective enzyme=Hexosimaminidase A
*build up of GM2

Front 130

lysosomal storage dz with:
-progressive neurodegeneration
-cherry red spot on macula
-hepatosplenomegaly


*name of dz?
*inheritance pattern
*defective enzyme
*build-up of what?

Back 130

Niemann-Pick
*AR
*defective enzyme=sphingomyelinase
*buildup of sphingomyelin

Front 131

lysosomal storage dz with:
-aseptic necrosis of femur
-bone crisis
-macrophages

*name of dz?
*inheritance pattern
*defective enzyme
*build-up of what?

Back 131

Gaucher's dz (*MC lysosomal storage dz)

[macrophages="Gaucher's bodies"]

*AR
*defective enzyme=Glucocerebrosidase
*buildup of glucocerebroside

Front 132

lysosomal storage dz with:
-peripheral neuropathy
-optic atrophy


*name of dz?
*inheritance pattern
*defective enzyme
*build-up of what?

Back 132

Krabbe's
*AR
*defective enzyme=Beta-galactosidase
*buildup of galactocerebroside

Front 133

lysosomal storage dz with:
-ataxia & dementia (d/t central and peripheral demyelination)


*name of dz?
*inheritance pattern
*defective enzyme
*build-up of what?

Back 133

Metachromatic Leukodystrophy
*AR
*defective enzyme=arylSULFAtase
*buildup of SULFAtides

Front 134

ketone bodies

Back 134

in DKA and starvation, liver converts FA & aa==>B-hydroxybutyrate (more) & acetoacetate

Front 135

essential FA's

Back 135

-linoleic and linolenic acids
-if linoleic acid==>arachidonic acid becomes essential

Front 136

HDL

Back 136

transfers cholesterol from periphery==>liver

Front 137

LDL

Back 137

transfers cholesterol from liver==>periphery

Front 138

describe the major apolipoproteins

Back 138

*A1: "A"ctivates LCAT (Lecithin-Cholesterol Acetyl Transferase, which esterifies cholesterol)

*B48: mediates chylomicron secretion

*B100:
binds LDL receptor (on liver)
mediates VLDL secretion

*CII: Co-factor ("C"o-factor) for lipoprotein lipase

E: mediates "E"xtra (remnant)uptake

Front 139

Chylomicron has which apolipoproteins?

Back 139

*A1=activates LCAT (Lecithin-Cholesterol Acetyl Transferase, which esterifies cholesterol)

*B48 (mediates chylomicron secretion)

CII: cofactor for lipoprotein lipase

E: mediates "E"xtra (remnant) uptake

Front 140

Chylomicron remnant has which apolipoproteins?

Back 140

*B48 (mediates chylomicron secretion)
*E (mediates "E"xtra (remnant) uptake)

Front 141

VLDL has which apolipoproteins?

Back 141

*B100 (binds LDL receptor (on liver))
*CII (cofactor for lipoprotein lipase)
*E: mediates "E"xtra (remnant) uptake

Front 142

IDL has which apolipoproteins?

Back 142

*B100 (binds LDL receptor (on liver))

*E: mediates "E"xtra (remnant) uptake

Front 143

LDL has which apolipoproteins?

Back 143

*B100 (binds LDL receptor, mediates VLDL secretion)

Front 144

excess of VLDL can cause what?

Back 144

pancreatitis

Front 145

HDL has which apolipoproteins?

Back 145

none

Front 146

pink urine
psychological disturbances
polyneuropathy

Back 146

porphyrias

Front 147

which form of Hg does CO2 prefer?

Back 147

prefers T (taut) form
[T is to the right==>thus, lower affinity for O2 (more O2 delivery to tissues) & thus higher affinity for CO2)

Front 148

what shifts oxygen dissociation curve to the right?

Back 148

incr H+ (acidic)
incr CO2 (acidic)
incr Cl
incr temp (fever)
incr 2,3-BPG

Front 149

variants of Hg

Back 149

both of these cause tissue hypoxia d/t decr O2 sat & decr O2 content:

1. Methemoglobin:
-oxidized form of iron (Fe3+, vs Fe2+), which cannot bind O2
but has incr affinity for CN-

(menum: Treat toxic levels of METHemoglobin w/METHylene blue)


2. Carboxyhemoglobin
-form of Hg bound to CO instead of O2

Front 150

Tx cyanide poisoning

Back 150

Give nitrites, these oxidize hemoglobin (Fe2+) to methemoglobin (Fe3+), which has high affinity for cyanide, so it binds the cyanide and reduces toxicity

Front 151

Northern, Southern, and Western blots

Back 151

Northern=RNA (w/DNA probe)
Southern=DNA (w/DNA probe)
Western=protein

Front 152

FISH

Back 152

Flourescence in situ hybridization (FISH):

fluorescent probe binds to specific gene of interest
==>specific localization of genes and direct visualization of anomalies

Front 153

incomplete penetrance

Back 153

not everyone with the mutant genotype expresses the mutant phenotype

Front 154

imprinting
-def
-ex

Back 154

-at a single locus, only one allele is active, the other is inactive. Deletion of active allele==>dz

-differences in phenotype depend on whether the mutation is of maternal or paternal origin

mneum:
1. angel"M"an's syndrome ("M"=Maternal)
-deletion of normally active maternal allele
-Sx:
*MR
*seizures
*ataxia
*inappropriate laughter ("happy angel")

2. Prader-willi syndrome
("P"=Paternal)

-deletion of normally active paternal allele
-Sx:
*MR
*obesity
*hypogonadism
*hypotonia

Front 155

anticipation

Back 155

severity of dz worsens or dz onset occurs earlier in subsequent generations, i.e. Huntington's

Front 156

loss of heterozygosity

Back 156

if pt inherits or develops a mutation in tumor suppressor gene, the complementary allele must be mutated/deleted in order for cancer to develop

*this is NOT true of oncogenes

Front 157

dominant negative mutation

Back 157

-mutation has DOMINANT effect
-in heterozygote, the mutated allele prevents other nl allele from functioning properly

Front 158

linkage disequilibrium

Back 158

tendency for certain alleles at 2 linked loci to occur together more frequently than expected by chance

Front 159

mosaicism

Back 159

cells in body have diff genetic makeup,

e.g. lyonization--random X inactivation in females

Front 160

locus heterogeneity:
-def
-ex

Back 160

mutations at diff loci can produce same phenotype

e.g. albinism

Front 161

assumptions for Hardy-Weinberg equil

Back 161

1. no mutation
2. no natural selection
3. no migration
4. random mating

Front 162

inheritance pattern if no father-son transmission

Back 162

x rec

Front 163

inheritance pattern if ALL daughters of affected father have dz?

example?

Back 163

x-linked dominant

e.g. Hypophosphatemic rickets

Front 164

inheritance pattern if transmitted only thru mother?

ex?

Back 164

mitochondrial inheritance

e.g. Leber's hereditary optic neuropathy

e.g. mitochondrial myopathies

Front 165

adult polycystic kidney dz
-inheritance pattern?
-desc
-assoc with what other abnl?

Back 165

-AD inheritance
(juvenile form is recessive)

-ALWAYS BILATERAL
-massive enlargement of both kidneys d/t many cysts
-mutated APKD1 gene (chrom 16; mneum: "You're an ADULT when you're 16 b/c you can drive")

Assoc w/:
-BERRY ANEURYSMS
-polcystic liver dz
-mitral valve prolapse

Front 166

familial hypercholesterolemia
-inheritance pattern?
-desc

Back 166

=Hyperlipidemia Type IIa

-AD

-defective/absent LDL receptor
==>incr LDL & chol

Heterozygotes:
-chol ~ 300

Homozygotes (very rare):
-chol > 700 !
-severe atherosclerosis at young age
-tendon xanthomas (esp Achilles tendon)
-MI before 20 y/o

Front 167

Marfan's
-inheritance pattern?
-desc

Back 167

-auto dom

-mutated fibrillin gene (ECM)==>CT abnl

A. Skeletal abnl:
tall w/long extremities (arachnodactyly)
hyperextensible fingers and joints
pectus excavatum

B. CV abnl:
cystic medial necrosis of Ao
==>Ao insufficiency
==>Ao dissection

C. Optic:
subluxation of lenses

Front 168

Neurofibromatosis--Type I
-inheritance pattern?
-desc

Back 168

AKA von Recklinghausen syndrome

-AD inheritance
-on long arm of Chrom 17 (mneum: von Recklinghausen has 17 letters)

-cafe au lait spots
-Sk abnl (scoliosis)

Incr tumor susceptibility:
-neural tumors
-optic gliomas
-pheochromocytoma

Front 169

Neurofibromatosis--Type II
-inheritance pattern?
-desc

Back 169

-AD inheritance
-NF2 gene on chrom 22 (mneum: Type "2"= "22")

-bilateral acoustic neuromas
-juvenile cataracts

Front 170

tuberous sclerosis
-inheritance pattern?
-desc

Back 170

-AD inheritance
-incomplete penetrance

-MR
-seizures
-facial lesions (adenoma sebaceum)
-hypopigmented "ash leaf" spots on skin
-cardiac rhabdomyomas

Hamartomas in:
*Brain: astrocyte proliferations
*retina
*kidney

(tuberous sclerosis, neurorfibromatosis, & Sturge-Weber all have abnl neuroectoderm & are AD.

Tuberous sclerosis sounds like Sturge-Weber. Sturge-Weber has port-wine nevus on face w/ipsilateral A-V malformations in the meninges beneath)

Front 171

Von Hippel-Lindau dz
-inheritance pattern?
-desc

Back 171

-AD inheritance

-deletion of tumor suppressor Von Hippel Lindau on Chrom 3p
(mneum: Von Hippel-Lindau = "3" words for Chrom "3")

-hemangioblastomas of retina/cerebellum/medulla

Front 172

Huntington's dz
-inheritance pattern?
-desc

Back 172

-AD inheritance
-triplet repeat d/o: incr CAG repests==>CAG repeats code for Glutamine==>hyperkinetic
-gene on chrom 4 (mneum: HUNTING 4 food)
-anticipation (dz severity/onset worsens in subsequent generations)

-depression
-progressive dementia
-choreiform mvmts
-caudate atrophy

Front 173

Familial Adenomatous Polyposis
-inheritance pattern?
-desc

Back 173

-AD inheritance
-at adolescence, colon becomes covered in adenomatous (gland-like) polyps
-must resect colon or else cancer develops

-deletion on chrom 5 (mneum: 5 letters in "polyp")

Front 174

hereditary spherocytosis
-inheritance pattern?
-desc
-Tx

Back 174

-AD inheritance

-sphere-shaped RBC's==>destroyed in spleen
==>hemolytic anemia
-inc MCHC

-Tx: splenectomy is curative

Front 175

inheritance pattern:
CF

Back 175

AR

Front 176

inheritance pattern:
albinism

Back 176

AR

Front 177

inheritance pattern:
alpha-1-antitrypsin deficiency

Back 177

AR

Front 178

inheritance pattern:
phenylketonuria

Back 178

AR

Front 179

inheritance pattern:
thalassemias

Back 179

AR

Front 180

inheritance pattern:
sickle cell anemia

Back 180

AR

Front 181

inheritance pattern:
glycogen storage dz's

Back 181

AR

Front 182

inheritance pattern:

mucopolysaccharidoses (the lysosomal storage dz's that are not sphingolipidoses)

Hurler's
Hunter's

Back 182

Hurler's: AR

Hunters: XR
(Hunters are aggressive (Sx: aggressive behavior, vs. Hurler's) & must have good eyes (no corneal clouding, vs. Hurler's) to aim for the "X" (XR).

Front 183

inheritance pattern:
sphingolipidoses

Back 183

AR (except Fabry's: X-rec)

Front 184

inheritance pattern:
infant polycystic kidney dz

Back 184

AR

Front 185

inheritance pattern:
hemochromatosis

Back 185

AR

Front 186

CF
-inheritance pattern
-desc
-Tx
-Dx

Back 186

-AR inheritance
-deletion of Phe 508 on CFTR gene (chrom 7)
==>mutant CFTR degrades in Golgi before reaching CM
==>incr Na+ reabs & decr Cl- secretion into duct lumens
(term bronchioles, panc ducts, liver)
==>thick, dehydrated mucus
==>obstructed ducts in

*LUNG==>recurrent pulmonary infxns:
*SA and Pseudomonas infxns
*chronic bronchitis
*bronchiectasis

GI (incl liver, pancreas)==>malabsorption of Vit ADEK

[CFTR usually absorbs Cl from sweat & secretes Cl into lung, liver, pancreas]

-infertility in males d/t absent vas deferens

*Tx: N-acetylcysteine (to loosen mucus plugs)
*Dx: sweat tests reveals high Cl- ions in sweat

Front 187

inheritance pattern:
Bruton's agammaglobulinemia

Back 187

X-rec

Front 188

inheritance pattern:
Wiskott-Aldrich

Back 188

X-rec (descr on FA p. 195 in immuno section)

Front 189

inheritance pattern:
Fragile X

Back 189

X-rec

Front 190

inheritance pattern:
Ocular albinism

Back 190

X-rec

Front 191

inheritance pattern:
Lesch-Nyhan syndrome

Back 191

X-rec

Front 192

inheritance pattern:
Duchenne's muscular dystrophy

Back 192

X-rec

Front 193

inheritance pattern:
Hemophilia A

Back 193

X-rec (for both Hemophilia A & B)

Front 194

inheritance pattern:
Hemophilia B

Back 194

X-rec (for both Hemophilia A & B)

Front 195

inheritance pattern:
Fabry's dz

Back 195

X-rec

(lysosomal--spingolipidosis dz)

Front 196

inheritance pattern:
Hunter's syndrome

Back 196

X-rec

(lysosomal storage dz-- mucopolysaccharidosis dz)

Front 197

Duchenne's muscular dystrophy
-inheritance pattern
-desc
-Dx?

Back 197

-X-rec
-Duchenne's= "D"eleted "D"ystrophin (d/t frameshift mutation)
==>accelerated muscle breakdown
-onset before 5 y/o
-weakness begins in pelvic girdle muscles and moves superiorly
-Gower's sign indicates proximal lower limb weakness

*Dx w/incr CPK & muscle biopsy

Front 198

Becker's muscular dystrophy
-desc
-Dx?

Back 198

MUTATED dystrophin gene (vs. DELETED dystrophin gene in Duchenne's muscular dystrophy)

*Dx w/incr CPK & muscle biopsy

Front 199

Fragile X syndrome
-inheritance pattern
-desc

Back 199

-X-rec
-triple repeat d/o (CGG)n on Chrom X (thus X-rec) in promotor region of FMR1 gene
==>altered methylation & expression of FMR1 gene

-genetic anticipation (more severe/earlier onset in subseuqent generations)

-2nd MCC MR (MCC=Down's)

Sx:
-macro-orchidism
-e"X"tra-large testes, jaw, ears

Front 200

#1 and #2 causes of MR

Back 200

#1=Down's
#2=Fragile X

Front 201

Trinucleotide repeat d/o

Back 201

mneum: "TRY (TRInucleotide) HUNTING for MY FRIED eggs (X)":

HUNTINGton's
MYotonic dystrophy
FRIEDreich's ataxia
fragile "X"

*anticipation (more severe and earlier onset in subsequent generations)

Front 202

decr alpha-FP

Back 202

Down's

Front 203

decr alpha-FP
incr beta-hCG
incr nuchal translucency

Back 203

Down's

Front 204

MC chromosomal d/o

Back 204

Down's

Front 205

MCC MR

Back 205

Down's

Front 206

Down's syndrome
-serum levels
-desc
-et

Back 206

-Trisomy 21
-MC chromosomal d/o
-MCC MR

Serum levels:
decr alpha-FP
incr beta-hCG
incr nuchal translucency

Sx:
-flat facial profile
-prominent epicanthal folds
-simian crease
-duodenal atresia
-cardiac abnl: septum primum-type ASD d/t endocardial cushion defects
-Alz Dz (>35 y/o)

Et:
95% d/t maternal non-disjxn during meiosis
4% d/t Robertsonian translocation
1% d/t Down mosaicism (no maternal association)

Front 207

Edward's syndrome
-desc
-prognosis

Back 207

-Trisomy 18 ("E"dwards="E"lection Age)

Sx:
-severe MR
-rocker bottom feet
-low-set ears
-prominent occiput
-micrognathia (small jaw)
-congenital heart dz
-clenched hands

Prognosis: death before 1 y/o

Front 208

Patau's syndrome
-desc
-prognosis

Back 208

-Trisomy 13 ("P"atau's="P"uberty age)

Sx:
-severe MR
-microcephaly
-micropthalmia
-cleft lip/palate
-abnl forebrain structures
-polydactyly
-congenital heart dz

Prognosis: death before 1 y/o

Front 209

Autosomal trisomies

Back 209

-Down's/Trisomy 21 ("D"="D"rinking age=21)

-Edward's/Trisomy 18 ("E"dward's="E"lection age=18)

-Patau's/Trisomy 13 ("P"atau's=Trisomy 13)

Front 210

cri-du-chat

Back 210

-congenital deletion of chrom 5p (46XX,5p- or 46XY,5p-)
-high pitched crying/mewing
-severe MR
-epicanthal folds
-cardiac abnl

Front 211

22q11 syndromes

Back 211

-microdeletion at chrom 22q11

mneum: "CATCH-22"

Cleft palate
Abnl facies
Thymic aplasia==>deficient T cells
Cardiac defects
Hypocalcemia (secondary to parathyroid aplasia)

Variable presentation as:
-DiGeorge syndrome (cardiac, thymic, or parathyroid defects)
-Velocardiofacial syndrome (cardiac, facial, palate defects)

Front 212

MCC congenital malformations in US

Back 212

Fetal Alcohol syndrome

Front 213

Fetal Alcohol Syndrome

Back 213

-MCC congenital malformations in US
-d/t excessive alcohol intake during wks 3-8 of gestation
-mechanism=inhibit cell migration

Sx:
-MR
-microcephaly
-facial abnl
-limb dislocation
-heart and lung fistulas