usmle's most wanted enzymes

8/9/2019 USMLE's Most Wanted Enzymes

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USMLE’s Most Wanted: Enzymes

By Chris “Captain High-Yield Way !"ho else#$Enzyme %&n'tion Chara'teristi's (e)'ien'y res&lts

in:*ly'olysis

Glucokinase Catalyzesphosphorylation o+

gl&'ose to gl&'ose-

,-phosphate in

liver and islet 'ells

-High K m:+&n'tions only

"hen

intra'ell&lar

gl&'ose in

hepato'yte is

eleated

-High Vmax:

allo"s lier to

remoe .ood o+

gl&'ose

deliered

-/0y ins&lin

-10y gl&'agonHe2o3inase Catalyzes

phosphorylation o+

gl&'ose to gl&'ose-

,-phosphate in

most tissues

-Lo" 4 m

-Lo" 5ma2

-10y gl&'ose-,-

phosphate

La'tate

dehydrogenase

Conersion o+

pyr&ate to la'tate

-Used only in

anaero0i'

gly'olysis-6eo2idizes

78(H to 78(

-La'ti' a'idosis:

drop in

intra'ell&lar pH

PFK-1

(phosphofructokina

se-1)

9hosphorylation o+

+r&'tose-,-

phosphate to

+r&'tose ;,-

0isphosphate

-Rate-limiting

step of

glycolysis

-10y 8<9; 'itrate

-/0y 8M9;

fructose 2!-"isphosphate

(most potent)9%4-=

!phospho+r&'to3inase

-=$

9hosphorylation o+

+r&'tose-,-

phosphate to

fructose 2!-

-/0y ins&lin

!dephosphorylati

on$

-10y gl&'agon



"isphosphate !phosphorylation

$

P#ruvate kinase Conersion o+ 9E9

to pyr&ate

-/0y +r&'tose

;,-

0isphosphate;

ins&lin-10y gl&'agon

!phosphorylation

$

-=nd most 'ommon

'a&se o+ enzyme

de)'ien'y-related

hemol#ticanemia

->n'reased B9*

'a&ses o2ygen

sat&ration '&re to

shi+t to right

-7o Heinz 0odies

!di?erent +rom

*,9( de)'ien'y$

-8&tosomal

re'essie9yr&ate

9yr&ate

dehydrogenase

Conersion o+

pyr&ate into

a'etyl Co8

-Coenzymes

re@&ired are

$H%&'%

pyrophosphate;

lipoi' a'id; Co8;

%8(; 78(H

-/0y ins&lin

!lier$; 'al'i&m;

pyr&ate

-10y a'etyl-Co8;8<9; 78(H

-A-lin3ed dominant

-*auses lactic

aci+osis

Citri' 8'id Cy'leCitrate synthase Condensation o+

a'etyl Co8 and

o2aloa'etate to

+orm 'itrate

-10y 'itrate;

78(H; s&''inyl

Co8

>so'itrate

dehydrogenase

2idatie

de'ar0o2ylation o+

iso'itrate to -

3etogl&tarate

-Major control

enzyme of the

TCA cycle

-10y 78(H; 8<9

-/0y 8(9;'al'i&m

-3etogl&tarate

dehydrogenase

Conersion o+ -

3etogl&tarate to

s&''inyl Co8

-Coenzymes

re@&ired are

$H%&'%

pyrophosphate;



lipoi' a'id; Co8;

%8(; 78(H

-/0y 'al'i&m

-10y 8<9; *<9;

78(H; s&''inyl

Co8*ly'ogenesis and gly'ogenolysis

*ly'ogen synthase Ma3es !-D$

lin3ages in

gly'ogen

-Rate-limiting

enzyme of

glycogen

synthesis

-/0y ins&lin;

gl&'ose-,-

phosphate

-10y gl&'agon

!lier$;

epinephrineBran'hing enzyme Hydrolyzes !-D$

0ond; trans+ers it

to another resid&e

and atta'hes it

"ith an !-D,$

0ond to 'reate a

0ran'h

-8nderson disease:

in+antile hypotoniaF

ery +e" 0ran'hes

*ly'ogen

phosphorylase

Brea3s !-D$

0onds; releasing

gl&'ose--phosphate &ntil

&nits remain

0e+ore a 0ran'h

point

-Rate-limiting

enzyme of

glycogenolysis-/0y 'al'i&m;

8M9;

epinephrine;

gl&'agon !lier$

-10y ins&lin; 8<9;

gl&'ose-,-

phosphate

-M'Cardle (isease

!m&s'le$: muscle

cramps,eakness after

exercise

-Hers disease

!hepati'$: mil+

h#pogl#cemia

!gl&'oneogenesis

still s&pplies

gl&'ose$(e0ran'hing enzyme Hydrolyzes the

!-D$ 0ond

nearest the 0ran'h

point; trans+ers it

to another resid&e;

then hydrolyzes

the !-D,$ 0ond;

releasing a single

gl&'ose

-Cori (isease: mild

hypogly'emiaF

lier enlargementF

single glucose

resi+ue outer

"ranch



Lysosomal ;-

gl&'osidase

(egrades gly'ogen

in the lysosome

-9ompe (isease:

car+iomegal#F

gly'ogen-li3e

material in

inclusion "o+ies

in the lysosomes*l&'oneogenesis

P#ruvate

car"ox#lase

Car0o2ylation o+

pyr&ate to

o2aloa'etate

-Biotin-

dependent

-/0y a'etyl-Co8

-6eplenishes

intermediates o+

the <C8 'y'le

and proides

s&0strates +or

gl&'oneogenesis

9E9-'ar0o2y3inase

!9E9C4$

Conerts 88 to

phosphoenolpyr&

ate !9E9$

-Uni@&e to

gl&'oneogenesis

-/0y gl&'agon;

'ortisol

-10y ins&lin

Fructose-1!-

"isphosphatase

Hydrolysis o+

+r&'tose ;,-

0isphosphate to

+r&'tose ,-

phosphate

-Key

regulatory site

of

gluconeogenes

is

-/0y 8<9-10y 8M9;

fructose 2!-

"isphosphate*l&'ose-,-

phosphatase

Hydrolysis o+

gl&'ose ,-

phosphate to

gl&'ose

-nly in the lier

-6e@&ired +or the

)nal step o+ 0oth

gly'ogenolysis

and

gl&'oneogenesis

-5on *ier3e

(isease: severe

h#pogl#cemia

!0oth

gl&'oneogenesis

and gly'ogenolysis

&na0le to prod&'e

gl&'ose$%atty 8'id Synthesis

&cet#l *o&

*ar"ox#lase

Car0o2ylation o+

a'etyl Co8 to

malonyl Co8

-Both rate-

limiting and

regulatory

step of FA

synthesis



-6e@&ires 0iotin;

8<9; C=

-/0y ins&lin;

'itrate

-10y gl&'agon;

epinephrine; 8M9%atty a'id synthase

!palmitate synthase$

Synthesizes

palmitate +rom an

a'etyl Co8;

malonyl Co8’s and

78(9H’s

-.e/uires

&0PH +rom

HM9 Sh&nt and

Mali' Enzyme

Mali' Enzyme 2idizes malate to

pyr&ate;

generating 78(9H

-&++itional

source of

&0PH;

s&pplementing

that +rom the

HM9 Sh&nt%8 Storage

*ly'erol G-9

dehydrogenase

6ed&'tion o+ (H89

to gly'erol G-

phosphate

-*ly'erol G-

phosphate is the

initial re'eptor o+

%8’s d&ring <8*

synthesis

->n 0oth lier and

adipose

-(H89 is +rom

gly'olysis*ly'erol 3inase Conersion o+ +ree

gly'erol to gly'erol

G-phosphate

-*ly'erol G-

phosphate is the

initial re'eptor o+

%8’s d&ring <8*

synthesis

->n the lier only

-*ly'erol is

released d&ring

5L(L meta0olism

0y lipoprotein

lipase%8 Mo0ilization and Cata0olism

Hormone sensitive

lipase

Hydrolyti' release

o+ %8’s and gly'erol

+rom <8* in the

adipose

-/0y gl&'agon;

epinephrine;

'ortisol

-10y ins&linCarnitine %orms a'yl'arnitine -n the o&ter -'#opathic



palmitoyltrans+erase >

!C9<->$; a3a

'arnitine

a'yltrans+erase-

!C8<-$

+rom +atty a'yl Co8 mito'hondrial

mem0rane

->mportant +or

allo"ing long-

'hain %8’s to

enter into themito'hondria

-10y malonyl

Co8

'arnitine

a'yltrans+erase

!C8<IC9<$

de)'ien'y:

ina0ility to 'arry

%8’s a'ross innermito'hondrial

mem0rane res&lts

in m&s'le a'hes;

"ea3nessF

proo3ed 0y

prolonged e2er'ise;

espe'ially i+ +astingCarnitine

palmitoyltrans+erase

>> !C9<->> or C8<->>$

<rans+er o+ a'yl

gro&p +rom

'arnitine to Co8;

regenerating

'arnitine and +atty

a'yl Co8

-n the inner

mito'hondrial

mem0rane

->mportant +or

allo"ing long-

'hain %8’s to

enter into the

mito'hondria%atty a'yl-C8

dehydrogenases

Conersion o+ +atty

a'yl Co8 to enoyl

Co8 in J-o2idation

- spe'ies; ea'h

"ith spe'i)'ity

+or either short;

medi&m; long; or

ery long 'hain

+atty a'ids

-MC8( !medi&m

'hain +atty a'yl

Co8

dehydrogenase$

de)'ien'y: seere

non3etoni'hypogly'emiaF

+icar"ox#lic

aci+emia9ropionyl-Co8

'ar0o2ylase

Car0o2ylation o+

propionyl Co8 to

methylmalonyl Co8

-6e@&ires 0iotin -7eonatal

3etoa'idosis +rom

+ail&re to

meta0olize

3etoa'ids prod&'ed

+rom threonine;

methionine; aline

K isole&'ine

-7o methylmaloni'

a'id&ria'eth#lmalon#l *o&

mutase

Conersion o+

methylmalonyl Co8

to s&''inyl Co8

-1 of r!n"s

that re#uire

$itamin B1

-S&''inyl Co8

-Peripheral

neuropath#

-Megalo0lasti'

anemia



'an +orm malate

and enter

gl&'oneogenesis

-7eonatal

3etoa'idosis +rom

+ail&re to

meta0olize

3etoa'ids prod&'ed

+rom threonine;methionine; aline

K isole&'ine

-Methylmaloni'

a'id&ria4etone Body Meta0olism

HM* Co8 synthase Com0ines a'etyl

Co8 "ith

a'etoa'etyl Co8 to

prod&'e HM* Co8

-6ate-limiting

step in 3etone

0ody synthesis

<hiophorase Conerts

a'etoa'etate to

a'etoa'etyl Co8 in

e2trahepati'

tiss&es

-ot present in

the liver

therefore the

liver cannot

meta"olie

ketone "o+ies%r&'tose Meta0olism

%r&'to3inase 9hosphorylates

+r&'tose to

+r&'tose -9

-9rimary

me'hanism +or

+r&'tose

phosphorylation

-(e)'ien'y is

0enign

-8&tosomal

re'essie

-ssentialfructosuria

&l+olase Cleaes +r&'tose -

9 to (H89 and

gly'eraldehyde

-Here+itar#

Fructose

%ntolerance3

intracellular

trapping of

inorganic

phosphate from

fructose 1-P

accumulation

causes severeh#pogl#cemia

letharg#

vomiting*ala'tose Meta0olism

*ala'to3inase 9hosphorylation o+

gala'tose to

*ala'tose m&st

0e

-*ala'tosemia and

gala'tos&ria



gala'tose -9 phosphorylated

to 0e

meta0olized

-*ala'titol

a''&m&lation

'a&sing 'atara'ts

early in li+eGalactose 1-P

uri+#ltransferase

Conersion o+

gala'tose -9 togl&'ose -9

-*lassic

Galactosemia3phosphate

se/uestering

from galactose

1-P accumulation

causing mental

retar+ation liver

+amage4

gala'tosemia and

gala'tos&riaF

gala'titol

a''&m&lation

'a&sing 'atara'ts

early in li+e 8ldose red&'tase -6ed&'es gl&'ose

to sor0itol

-Conerts

gala'tose to

gala'titol

Sor0itol and

gala'titol are

osmoti'ally

a'tie and 'a&se

'atara't

+ormationHe2ose Monophosphate !HM9$ Sh&nt

Glucose !-P+eh#+rogenase

>rreersi0leo2idation o+

gl&'ose ,-9 to ,-

phosphogl&'onola'

tone

-Regulatoryenzyme of the

%M& 'hunt

-.esponsi"le to

form &0PH

-/0y ins&lin;

78(9

-10y 78(9H

-Most commondisease

producing

enzyme

a(normality

-'ost common

cause of

en#me-

+e5cienc#

relate+

hemol#tic

anemia

-Hein "o+ies <rans3etolase >nter'onersions o+

+r&'tose ,-9 and

gly'eraldehyde G-9

into ri0ose -9

0ypassing gl&'ose

6e@&ires

thiamine



,-9 dehydrogenase78(9H o2idase Conerts mole'&lar

o2ygen into

s&pero2ide

-Lo'ated in

le&3o'yte 'ell

mem0rane

-4ills 0a'teria

-6e@&ires 78(9H

-*hronic

Granulomatous

0isease3 seere

persistent

in+e'tions!'atalase

0a'teria$ and

gran&loma

+ormationCholesterolILipoprotein Meta0olism

H'G-*o&

.e+uctase

6ed&'tion o+ HM*

Co8 to mealoni'

a'id

-Rate-limiting

and )ey

regulatory

step in

cholesterol

synthesis

-/0y ins&lin; 8M9

-10y gl&'agon;

'holesterol;

statins6ipoprotein lipase Hydrolyzes <8* o+

5L(L and

'hylomi'rons to

%8’s and gly'erol

-7"# apo *-%%

insulin

-<ype >

hyperlipidemia:

+amilial lipoprotein

lipase de)'ien'y

res&lts in

h#perch#lomicronemia re+-

orange

xanthomas Cholesterol ester

trans+er protein

!CE<9$

<rans+er o+

'holesterol esters

+rom H(L to 5L(L

in e2'hange +or

<8* or

phospholipids

6esponsi0le +or

>(L’s a'@&iring

CE’s +rom H(L

and 0e'oming

'onerted to

L(L’s8'yl Co8:'holesterol

a'yltrans+erase!8C8<$

<rans+ers a %8 +rom

a +atty a'yl Co8deriatie to

'holesterol;

pro+ucing a

cholesterol ester

for storage "hen

'holesterol is not

8'tiity is

enhan'ed in thepresen'e o+

/intra'ell&lar

'holesterol



re@&iredLe'ithin-'holesterol

a'yltrans+erase

!LC8<$ a3a

phosphatidyl'holine-

'holesterola'yltrans+erase

!9C8<$

<rans+ers a %8 +rom

phosphatidyl'holin

e to 'holesterol

"hen 'holesterol is

ta3en &p 0y H(L;prod&'ing

'holesterol esters

"hi'h dissole in

the 'ore o+ the H(L

-Enzyme in the

0lood

-&ctivate+ "#

&po &-% on H06

6emoal o+ 7itrogen +rom 88’s*l&tamine synthetase 8minates

gl&tamate to +orm

gl&tamine

-*l&tamine is

maNor 'arrier o+

e2'ess nitrogen

+rom tiss&es*l&taminase Eliminates amino

gro&p o+ gl&tamineas +ree ammonia

-Enzyme leels

are high in the3idney and the

intestine8minotrans+erases <rans+ers amino

gro&p +rom one

'ar0on s3eleton

!an amino a'id$ to

another !&s&ally -

3etogl&tarate$

-9yrido2al

phosphate

deried +rom

vitamin ! is

re@&ired to

mediate the

trans+er

-8mino gro&ps o+ most 88’s are

+&nneled onto -

3etogl&tarate to

prod&'e

gl&tamate

-Eleated ser&m

leels o+ 8L<; 8S<

+rom lier

damage*l&tamate

dehydrogenase

2idatiely

deaminatesgl&tamate to -

3etogl&tarate;

li0erating the

amino gro&p as

free ammonia

--3etogl&tarate

is a <C8 'y'leintermediate

-/0y 8(9

-10y *<9

Urea Cy'le



Car0amoyl phosphate

synthetase >

-%ormation o+

'ar0amoyl

phosphate +rom

ammoni&m ion;

'ar0on dio2ide;

and = 8<9

-Rate-limiting

step in the

urea cycle

-Mito'hondrial

enzyme

-/0y 7-a'etylgl&tamate

-Hyperammonemia

-7o in'rease in

&ra'il or oroti' a'id

-Mental retardation

-/0lood gl&tamine

!0ody’s attempt toremoe 7H$

-1BU7rnithine

trans'ar0amoylase

%ormation o+

'itr&lline +rom

ornithine and

'ar0amoyl

phosphate

-Citr&lline enters

the 'ytoplasm

-Most 'ommon

enzymati'

de)'ien'y o+ the

&rea 'y'le

-A-lin3ed

-Hyperammonemia

-Ura'il and oroti'

a'id in'rease

-Mental retardation

-/0lood gl&tamine

-1BU78rginase Cleaes arginine to

ornithine and urea

-Last enzyme o+

the &rea 'y'le

-E2'l&siely in

the liver so only

the lier 'an

synthesize &rea8mino 8'id Cata0olism

Phen#lalanineh#+rox#lase

Hydro2ylation o+phenylalanine to

tyrosine

-%irst rea'tion inthe 'ata0olism o+

phenylalanine

-6e@&ires BH

!tetrahydro0iopt

erin$ as a

'oenzyme

-Phen#lketonuria(PK8) is the most

'ommon in0orn

error o+ 88

meta0olism:

-Eleated

phenylalanine

-Mental retardation

-M&sty odor to the

&rine +rom

/phenylpyr&ate;

phenylla'tate K

phenyla'etate

-Hypopigmentation

-Mi'ro'ephaly i+

pregnant "oman

"ith 94U gies

0irth



Homogentisate

o2idase

Conersion o+

homogentisate to

maleyla'etoa'etat

e

-&lkaptonuria3

-Homogentisi'

a'id&ria O dar3

&rine

-'hronosis

-&rthritis ranche+-chain

ketoaci+

+eh#+rogenase

2idatie

de'ar0o2ylation o+

-3etoa'ids

deried +rom

leucine valine

an+ isoleucine

-Coenzymes

re@&ired are

$H%&'%

pyrophosphate;

lipoi' a'id; Co8;

%8(; 78(H

-'aple 9#rup

8rine 0isease3

-8&tosomal

re'essie

-Leels o+

0ran'hed 'hain

88’s and their -

3eto analogs are

eleated

-Maple syr&p odor

to the &rine

-Mental retardation

-4etosisHomo'ysteine methyl

trans+erase

!methionine

synthase$

Methylation o+

homo'ysteine to

methionine

-6e@&ires 7-

methyl $HF as

methyl donor

-6e@&ires

methyl'o0alamin

; a 'oenzyme

deried +rom

vitamin 12

-Homoc#stinemia

!&s&ally 'a&sed 0y

itamin

de)'ien'ies o+

+olate; B= K B,$:

-/ris3 +or

atheros'lerosis;

(5<; stro3e

Cystathione J-

synthase

Condensation o+

homo'ysteine "ith

serine; +orming

'ystathionine;

"hi'h is

hydrolyzed to

'ysteine K -

3eto0&tyrate;

"hi'h is

o2idatiely

de'ar0o2ylated to

+orm propionyl-Co8

-6e@&ires

vitamin !

-Homoc#stinuria3

-High leels o+

homo'ysteine K

methionine in the

&rine

-8theros'lerosis in

'hildhood

-E'topia lentis

!displa'ement o+

the lens$

-Mental retardation

Heme Synthesis8L8 Synthase Condenses gly'ine

and s&''inyl Co8

-Rate-limiting

step in



to +orm 8L8 porphyrin

(iosynthesis

-6e@&ires itamin

B,

-10y heme;

hemin8L8 dehydratase Condensation o+

t"o mole'&les o+

8L8 to +orm

porpho0ilinogen

10y lead; heay

metal ions

Hydro2ymethyl0ilane

synthase

Condensation o+

+o&r

porpho0ilinogens

to prod&'e

hydro2ymethyl0ila

ne

-&cute

%ntermittent

Porph#ria:

-7o

photosensitiity

-8&tosomal

dominant

-(ar3 port-"ine

&rine +rom

a''&m&lation o+

porpho0ilinogen

and 8L8 in the

&rineUroporphyrinogen

de'ar0o2ylase

(e'ar0o2ylation o+

&roporphyrinogen

>>> to

'oproporphyrinogen >>>

-Porph#ria

cutanea tar+a:

the most 'ommon

porphyria-S3in lesions

-9hotosensitiity

-6ed-"ine &rine

+rom a''&m&lation

o+ &roporphyrin in

the &rine%erro'helatase %ntro+uction of

iron into

protoporphyrinoge

n >A to +orm heme

10y lead; heay

metal ions

->ron de)'ien'y

prod&'es a

mi'ro'yti'

hypo'hromi'

anemia

-Erythropoieti'

protoporphyria

+rom

+erro'helatase

de)'ien'y: s3in

rashes and 0listers



in early 'hildhoodHeme (egradation

iliru"in glucuron#l

transferase

ConN&gates

0ilir&0in in the lier

to t"o mole'&les

o+ gl&'&roni' a'idto +orm 0ilir&0in

digl&'&ronide

!'onN&gated

0ilir&0in$

-Crigler-7aNNar

syndrome:

'omplete loss;

in'ompati0le "ithli+e

-*il0ert syndrome:

slight de+e't

-9hysiologi'

Na&ndi'e in the

ne"0orn;

espe'ially

premat&re in+ants

!enzyme not +&lly

ind&'ed$

-Un'onN&gated

!indire't$ 0ilir&0in

in'rease O

Na&ndi'e9&rine Synthesis

9699 Synthetase Synthesis o+ 9699

+rom 8<9 and

ri0ose -phosphate

-/0y inorgani'

phosphate

-10y p&rine

n&'leotides9699

8midotrans+erase

Synthesis o+ -

phosphori0osylamine +rom 9699 and

gl&tamine

-Rate-limiting

step of deno$o purine

synthesis

-/0y 9699

-10y 8M9; >M9;

*M9

-10y allop&rinol;

,-

mer'aptop&rine9&rine Cata0olism and Salage

8denosine deaminase 8mino gro&p is

remoed +romadenosine to

prod&'e inosine

-8&tosomal

re'essie-Seere 'om0ined

imm&node)'ien'y

!SC>($H#poxanthine-

guanine

phosphori"os#ltran

Salages p&rine

0ases

hypo2anthine and

-6e@&ires 9699

as so&r'e o+

ri0ose -

-6esch-#han

9#n+rome3

-A-lin3ed re'essie



sferase (HGP.$) g&anine to >M9;

*M9; respe'tiely

phosphate ->na0ility to

salage

hypo2anthine or

g&anine O

e2'essie &ri' a'id

prod&'tion Ohyper&ri'emia

-Sel+-m&tilation

!hands; lips$

-Spasti' 'ere0ral

palsy

-Mental retardationAanthine o2idase 2idation o+

hypo2anthine to

2anthine; "hi'h is

+&rther o2idized to

uric aci+ the

5nal pro+uct of

purine

+egra+ation

10y allop&rinol

9yrimidine Synthesis and (egradationCar0amoyl phosphate

synthetase >>

Synthesis o+

'ar0amoyl

phosphate +rom

gl&tamine and C=

-Regulated

step of

pyrimidine

synthesis

-/0y 8<9; 9699

-10y U<9UM9 Synthase

!orotate

phosphori0osyltrans+

erase and M9

de'ar0o2ylase$

=-step 'onersion

o+ oroti' a'id to

UM9

-:rotic &ci+uria3

-8&tosomal

re'essie

-Megalo0lasti'

anemia

-rotate in the

&rine

-6ack of

h#perammonemi

a (r;o :$*

+e5cienc#)6i0on&'leotide

red&'tase

6ed&'tion o+

n&'leoside

diphosphates to

their deo2y- +orms

-10y d8(9; d8<9

-10y

hydro2y&rea

<hymidylate synthase -Conersion o+

dUM9 to d<M9 +or

-6e@&ires

77Pmethylene



(78 synthesis

-2idizes <H% to

(H%

$HF as methyl

donor

-10y -

.&oro&ra'il(ihydro+olate

red&'tase

-=-step red&'tion

o+ +olate to (H%;and o+ (H% to <H%

-10y

methotrexate !e&3aryoti'$;

trimethoprim

!pro3aryoti'$;

pyrimethamine

!protozoal$

-6e@&ires 78(9H

-<H% is a methyl

donor

-%olate de)'ien'y:

megalo0lasti'anemia;

homo'ystinemia;

7<(’s in +et&s

Collagen Biosynthesis9rolyl hydro2ylase;

lysyl hydro2ylase

-Hydro2ylation o+

proline to

hydro2yproline;

hydro2ylation o+

lysine to

hydro2ylysine;

respe'tiely

-ecessar# for

h#+rogen

"on+ing ,ithin

the triple helices

-.e/uire

vitamin *

-9curv#3

-Se'ondary to

as'or0ate

de)'ien'y

-9ete'hiae;

e''hymoses; loose

teeth; 0leeding

g&ms; poor "o&nd

healing

-hlers-0anlos

s#n+rome3

-Lysyl hydro2ylasede)'ien'y

-Hypere2tensi0le;

+ragile s3in;

hypermo0ile Noints

-8rterial; intestinal

r&pt&resLysyl o2idase %mportant for

forming covalent

cross-links an+

thus mature

collagen 5"ers

-*opper-

+epen+ent

-'enkes

0isease3

-(&e to +&n'tional

'opper de)'ien'y

-A-lin3ed re'essie:

m&tations in 8<9Q8

-Copper 'annot 0e

transported into

the 0loodstream:

lo" leels o+

'opper and



'er&loplasmin

-(epigmented

3in3y hair; arterial

r&pt&re !"ea3

'ollagen$; 'ere0ral

degeneration;hypothermia;

'ere0ral

hemorrhage(78 6epli'ation

Heli'ase Un"inds the (78

do&0le heli2

-Uses 8<9 to

0rea3 H-0onds

holding 0ase

pairs together

-Ca&ses (78

ahead o+

repli'ation +or3

to 0e'ome

oer"o&nd and

to +orm positie

s&per'oils 9rimase Synthesizes 678

primer in ’ to G’

dire'tion

6e@&ired

0e'a&se (78

polymerases 'an

only e2tend a

strand +rom the

G’ end(78 polymerase >

!pro3aryoti'$

-6emoes 678

primers ia ’ to G’

e2on&'lease

-Synthesizes (78

to )ll in res&lting

gaps

Can proo+read

ia G’ to ’

e2on&'lease

(78 polymerase >>>

!pro3aryoti'$

Synthesizes (78 in

’ to G’ dire'tion;

0eginning R G’ end

!ie o+ a 678

primer$

Can proo+read

ia G’ to ’

e2on&'lease

(78 polymerase

!e&3aryoti'$

-Contains primase

->nitiates (78

synthesis !’ to G’

polymerase

a'tiity$(78 polymerase Elongates leading Can proo+read



!e&3aryoti'$ strands and

3aza3i +ragments

ia G’ to ’

e2on&'lease(78 polymerase T

!e&3aryoti'$

6epli'ates

mito'hondrial (78(78 polymerase J;

!e&3aryoti'$

(78 repair

(78 ligase -Voins 3aza3i

+ragments 0y

+orming 9(E 0onds

-%ormation o+ 9(E

0ond at a 0rea3 in

a (78 strand

<opoisomerase > 6eliees (78

s&per'oiling ia

0rea3ing and

resealing o+ (78

strand(78 gyrase

!topoisomerase >>$

6eliees (78

s&per'oiling 0y

ni'3ing 0oth

strands o+ (78 and

then resealing

10y @&inolones

and

.&oro@&inolones;

there0y

preenting (78

repli'ation K

trans'ription

-E&3aryoti'

topoisomerase >>

is 10y etoposide;teniposide

!antineoplasti's$ <elomerase Maintains

telomeres that

other"ise "o&ld 0e

lost d&ring

repli'ation;

preenting

apoptosis

9resent only in

em0ryoni' 'ells;

germ 'ells; stem

'ells; and 'an'er

'ells

6eerse trans'riptase 678-dependent

(78 polymerase synthesizes (78

+rom 678

-9resent in

retroir&ses-La'3s

proo+reading

-10y 8X<; ddC;

dd>(78 6epair

E2'ision

endon&'lease

6emoes thymine

dimers that +orm

Ma3es ni'3s in

9(E 0a'30one O

<ero+erma

pigmentosum



+rom U5 light remoes thymine

dimer O (78

polymerase )lls

in gap O (78

ligase seals ni'3

-8&tosomal

re'essie

-E2treme U5

sensitiity

-M&ltiple s3in

'an'ers-Corneal

&l'erations

-S3in +re'3ling <rans'ription and 678 9ro'essing

678 polymerase

!pro3aryoti'$

Synthesizes all

types o+ 678 in the

'ell e2'ept +or 678

primers

-10y ri+ampin;

a'tinomy'in (

-6e@&ires

+a'tor +or

initiation o+

trans'ription:

ena0les

re'ognition o+

promoter regions

-<erminates "hen

termination

signal is rea'hed:

either *-C ri'h

hairpin loop

+ollo"ed 0y ,-Z U

resid&es is

+ormed topromote

disso'ation; or [

!rho$ +a'tor

displa'es 678

polymerase678 polymerase >

!e&3aryoti'$

Synthesizes r678

e2'ept +or S r678678 polymerase >>

!e&3aryoti'$

Synthesizes m678;

sn678

-10y -amanitin

!to2in +rom

poisono&s

m&shroom

Amanita

phalloides);

a'tinomy'in (

-<rans'ription

+a'tors ! <%>>($

help initiate



trans'ription678 polymerase >>>

!e&3aryoti'$

Synthesizes t678

and S r678 <ranslation

8minoa'yl-t678

synthetase

Catalyzes =-step

rea'tion that'oalently

atta'hes 'ar0o2yl

gro&p o+ 88 to G’

end o+ 'orre't

t678

-6e'ognizes

spe'i)' 88 andthe t678 that

'orresponds to it

-Has

proo+reading

+&n'tions to

preent

in'orre'tly paired

aminoa'yl

t678’s +rom

+orming

-6e@&ires 8<9E%-<& and E%-<s

!pro3aryoti'$F eE%-

!e&3aryoti'$

Elongation +a'tors

that dire't 0inding

o+ the appropriate

t678 to the 'odon

in the empty 8 site9eptidyl trans+erase -Catalyzes peptide

0ond +ormation

0et"een 'ar0o2y

gro&p in 9 site and

amino gro&p in the8 site

->nd&'ed 0y

release +a'tors to

hydrolyze 0ond

lin3ing peptide to

the t678 R the 8

site; 'a&sing the

nas'ent protein to

0e released

-8 ri0ozyme

!'atalyti' 678

spe'ies$ part o+

the large s&0&nit

-10y'hlorampheni'ol

!pro3aryoti'$

E%-* !pro3aryoti'$F

eE%-= !e&3aryoti'$

Elongation +a'tors

re@&ired +ortranslo'ation o+

the ri0osome

-eE%-= is 1ia

8(9-ri0osylation0y (iphtheria;

9se&domonas

to2in9hosphotrans+erase 9hosphorylation o+

mannose resid&es

on lysosomal

%-*ell 0isease

-8''&m&lation o+

s&0strates



enzymes in *olgi

to dire't them to

the lysosome

normally degraded

0y lysosomal

enzymes

->n'l&sion 0odies

-Coarse +a'ial

+eat&res-9sy'homotor;

gro"th retardation

-Cardiorespiratory

+ail&reM&'opolysa''haridoses !a''&m&lation o+ gly'osaminogly'ans d&e to de)'ien'y o+

lysosomal enzymes inoled in degradation o+ heparan andIor dermatan s&l+ate$

α-L->d&ronidase Lysosomal

degradation o+

dermatan and

heparan s&l+ate

Hurler 9#n+rome

('P9 %)

-8&tosomal

re'essie

-Corneal 'lo&ding;

mental retardation;

deelopmental

delay; gargoylism;

&pper air"ay

o0str&'tion;

hepatosplenomega

ly

-(eposition in

'oronary artery

leads to is'hemiaand early death

>d&ronate s&l+atase Lysosomal

degradation o+

dermatan and

heparan s&l+ate

Hunter

9#n+rome ('P9

%%)

-A-lin3ed re'essie

-7o 'orneal

'lo&ding

-Mild physi'al

de+ormity; mental

retardation

-8ggressie

0ehaiorSphingolipidoses !a''&m&lation o+ sphingolipids d&e to de)'ien'y o+ lysosomal

enzymes in sphingolipid degradation$Sphingomyelinase (egradation o+

sphingomyelin

"ithin lysosomes

iemann-Pick

0isease

-8&tosomal



o+ the C7S and the

reti'&loendothelial

system !di?erent

+rom <ay-Sa'hs$

re'essie

-8sh3enazi Ve"s

-

Hepatosplenome

gal# (+i=erent

from $a#-9achs)-

7e&rodegeneration

and mental

retardation

-Cherry-red spot on

ma'&la

-Chara'teristi'

+oamy

ma'rophages

!soap 0&00le

appearan'e o+ the

'ytoplasm$He2osaminidase 8 (egradation o+

*M= ganglioside

"ithin lysosomes

o+ the C7S and

retina

$a#-9achs

0isease

-8sh3enazi Ve"s

-8&tosomal

re'essie

-Cherry red ma'&la

-9sy'homotor

retardation; m&s'le

"ea3ness;seiz&res; dea+ness

-Blindness*l&'o'ere0rosidase (egradation o+

gl&'o'ere0rosides

in the lysosomes o+

the

reti'&loendothelial

system

Gaucher 0isease

-Most 'ommon

lysosomal storage

disorder

-8sh3enazi Ve"s

-8&tosomal

re'essie

-Hepatosplenomega

ly

-Chara'teristi'

ma'rophages "ith

tiss&e paper-li3e

'ytoplasm

-steoporosis o+



long 0ones

-9an'ytopenia;

throm0o'ytopenia

*ala'to'ere0rosidase (egradation o+

gala'to'ere0roside

s

Kra""e 0isease

-8&tosomal

re'essie-*lo0oid 'ells in

"hite matter o+

0rain

-9eripheral

ne&ropathy

-Mental and motor

deterioration

-Blindness and

dea+ness

α-gala'tosidase 8 (egradation o+

glo0osides

Fa"r# 0isease

-A-lin3ed re'essie

-4idneyIheart

+ail&re

-9eripheral

ne&ropathy o+

handsI+eet

-6eddish-p&rple

s3in rash

-B&rning pain in

lo"er e2tremities

8ryls&l+atase 8 (egradation o+s&l+atides

'etachromaticleuko+#stroph#

-8&tosomal

re'essie

-(emyelination

"ith ata2ia

-9rogressie

paralysis

-(ementia

-7eres stain

yello"ish-0ro"n

"ith 'resyl iolet

!meta'hromasia$8ra'hidoni' 8'id Meta0olism

9hospholipase 8= 6elease o+

ara'hidoni' a'id

+rom mem0rane-

0o&nd

"#

corticosteroi+s



phospholipids-Lipo2ygenase Conerts

ara'hidoni' a'id to

-H9E<E; the

le&3otriene

pre'&rsor!le&3otrienes are

mediators o+

allergi' response

and in.ammation$

-7ot a?e'ted 0y

7S8>(s

-↓ 0y Xile&ton

Cy'loo2ygenase- -Made

'onstit&tiely in

most tiss&es

-'aintenance of

gastric an+ renal

function an+

platelet

aggregation

"# 9&%0s

acetaminophen

aspirin

Cy'loo2ygenase-= -%n+uci"le in

response to

a'tiated imm&ne

and in.ammatory

'ells

-'e+iates the

in>ammator#

response

"# c#tokines

en+otoxin

gro,th factors

tumor

promotors

"# 9&%0s

acetaminophen

aspirin

selective *:<-2inhi"itors (i?e?

celecoxi")Ethanol Meta0olism

8l'ohol

dehydrogenase

-Conerts ethanol

to a'etaldehyde

-Conerts

methanol to +ormi'

a'id !to2i'$

-6ed&'tion o+

78( to 78(H

-Lo'ated in 'ytosol

"#

fomepiole

(anti+ote to

methanol)

8'etaldehyde

dehydrogenase

-2idizes

a'etaldehyde to

a'etate

-6ed&'tion o+

78( to 78(H

-Lo'ated in

"# +isul5ram



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