Step 1 Biochemistry

Front 1

Pyruvate kinase deficiency

Back 1

Glycolytic enzyme deficiency

Pres: Hemolytic anemia d/t inability to maintain Na/K- ATPase --> RBC swelling/lysis.

Also caused by phosphoglycose isomerase deficiency.

Hint 1

Glycolysis

Front 2

A muscle biopsy reveals elevated glycogen, elevated F6P, and decreased pyruvate. What is the deficient ENZ?

Back 2

PFK1

Most likely ENZ deficiency because the substrate just before has accumulated.

Hint 2

Most likely.

Front 3

RLS of glycolysis?

Back 3

PFK-1

Stimulated by AMP (need more ATP) and F26BP (fed state indicative via stim of PFK-2 by insulin)

Inhibited by ATP (enough ATP) and Citrate (product of TCA cycle)

Hint 3

Catalyzes F6P --> F16BP step, just before F16BP is split to GA3P and Dihydroxyacetone-P

Front 4

RLS of Gluconeogenesis?

Back 4

F16-bisphosphatase

Accomplished in liver.

Stimulated by ATP (enough ATP, need to store Energy/share it with other cells)

Inhibited by AMP (need more ATP), and F26-BP (fed state, should make E) - molecules of E deficiency.

Requires Mg2+ to function.

Hint 4

Catalyzes F16BP-->F6P step in the liver of gluconeogenesis, and in the Calvin cycle (reverse of PFK-1 in glycolysis).

Front 5

RLS of TCA (Krebs) cycle?

Back 5

Isocitrate Dehydrogenase

Hint 5

Catalyzes Isocitrate --> alpha-KG (yielding CO2 + 1NADH).

Front 6

RLS of Glycogen synthesis?

Back 6

Glycogen synthase

NOTE: glucose--> G6P--> G1P in glycogen synthesis!!

Also, UDP-glucose pyrophosphorylase primes the glucose to be attached to the growing glycogen chain.

Attached to the molecule by glycogen synthase (makes alpha-1,4 bonds.

Branching enzyme makes branches (and alpha-1,6 linkages).

Skeletal muscle and Hepatocytes.

Hint 6

Catalyzes UDP-glucose --> Glycogen, along with Branching ENZ

Front 7

RLS of glycogenolysis?

Back 7

Glycogen phosphorylase

inhibited by ATP (enough!), and glucose (why break it down when you've already got it goin'?)

Alpha-1,6 glucosidase AKA de-branching ENZ - breaks it down directly into glucose.

Hint 7

Catalyzes alpha-1,4 glycosidic linkage break to release G1P.

Glucose-6-phosphatase is absent in muscles. This is the last step to gen glucose for gluconeogenesis and glycolysis...this is why muscles are so selfish.

Front 8

RLS of HMP shunt?

Back 8

G6P-DH

Hint 8

Catalyzes G6P --> 6-phosphoglyconolactone to generate more NADPH and pentose sugars.

Function of PPP:
Generate reducing equiv (NADPH) [60% of total NADPH production]
Produce R5P (used to synth nucleotides/nucleic acids
Produce E4P used to synth aromatic AA
Digest dietary pentose sugars to form glycolytic intermediates

Most active in liver, mammary, and adrenal gland

Front 9

RLS of de-novo pyramidine synthesis?

Back 9

CPS-II

carbamoyl phosphate II

Hint 9

catalyzes conversion of ATP, CO2, and glutamine to Carbamoyl-P, which is then coverted to base (orotic acid).

Front 10

RLS of de novo purine synthesis?

Back 10

PRPP-amidotransferase

Hint 10

HINT: PUR As Gold.

catalyzes PRPP --> phosphoribosyl amine.

Front 11

Purine salvage abnormalities?

Back 11

HGPRT - lesch-nyhan
XLR

Adenosine deaminase deficiency
Auto recessive

Hint 11

HGPRT - catalyzes guanine-->GMP AND hypoxanthine -->IMP.

Defective purine salvage results in XS uric acid production and de novo purine synthesis.

Hint: He's Got Purine Recovery Trouble.

Adenosine deaminase def:

catalyzes adenosine-->Inosine. Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase. Prevents DNA synthesis and decreases lymphocyte count.

A major cause of SCID.

Hint: SCID happens to Kids.

Front 12

Malate aspartate shuttle

Back 12

Heart, liver

Hint 12

Gen 32 ATP per molecule

Front 13

G3P shuttle

Back 13

Muscles

Hint 13

Generate 30 ATP, less efficient

Front 14

GLUT-1

Back 14

RBC, brain - insulin-independent

Hint 14

Only E metabolite they recognize

Front 15

GLUT-2

Back 15

hepatocytes, beta cells of pancreas

Front 16

GLUT-4

Back 16

insulin-dependent
skeletal muscle, adipose tissue

Hint 16

only when you need to bring Glucose in according to systemic levels

Front 17

Hexokinase vs. Glucokinase

Back 17

Glucokinase - high Km, high Vmax

beta cells, hepatocytes

Hexokinase - low Km (high affinity for glucose), low vMax
not induced by insulin!

Hint 17

difference between cells that regulate glucose metabolism vs. those that need glucose less conditionally.

Front 18

Regulation of Pyruvate kinase

Back 18

Stim by F16BP (upstream substrate)

Inhib by ATP and alanine (indicates that you have plenty of E)

Hint 18

Catalyzes PEP --> pyruvate (last step before entering TCA cycle.

Front 19

Regulation of intracellular F26BP levels?

Back 19

PFK-2 increases levels of F26BP

FBP2 decreases levles of F26BP

Hint 19

PFK2 is stimulated by insulin in FED STATE. Converts F6P to F26BP (take it away from gluconeogenesis). F26BP stimulates PFK1 to convert F6P to F16BP --> glycolysis.

FBP2 is stimulated in FASTING STATE, and converts F26BP to F6P (enter into gluconeogenesis).

Front 20

Thiamine in TCA cycle

Back 20

Vitamin B1

These dehydrogenase reactions generate NADH in the mitochondria which enter the electron transport chain to generate ATP, therefore the patient has a problem making ATP.

Cofactors required by the above 2 enzymes are
Thiamine
Lipoic acid
CO2
Folate
NAD+
Which can be remembered by the phrase, "Tender Love and Care for Nancy"

Hint 20

Oxidative decarboxylation in TCA cycle

Front 21

Epinephrine's effect on glycolysis (specifically, its effect on liver, pancreas, and muscles).

Back 21

1. Liver: Stimulates Beta-2 receptors --> glycogen breakdown.

2. Pancreas: Stimulates glucagon release (+ adenylate cyclase --> increased cAMP --> more active FBP2 --> converts F2,6BP --> F6P; less PFK2 active --> less activation of PFK1 --> less activation of glycolysis.

3. Muscles: + beta-2 receptors to break down glycogen to glycose. Muscle doesn't respond to glucagon, so F26BP increases --> activates PFK1 --> more glycolysis. SUGAR WHERE YOU NEED IT.

Hint 21

Hint - think of whatchu gotta do when you fightin' or flightin'

Front 22

What cofactor does Pyruvate carboxylase require?

Back 22

Biotin

Pyruvate carboxylase catalyzes conversion of pyruvate directly to OAA.

Stimulated by Acetyl co-A (plenty of E around, so need to go back up pathway).

Hint 22

Carboxylation requires biotin.

Front 23

Key steps of Gluconeogenesis?

Back 23

Key ENZ highlighted:
Pyruvate carboxylase (+biotin)
PEP carboxylase
F16BPase
G6Pase

Occurs in cells designed to share glucose:
Liver hepatocytes, kidney, intestinal epithelium

Happens because you don't have much glucose in your blood. Liver shares glycogen stores, and forms pyruvate to go into glycolysis.

Hint 23

Muscles don't have glucose 6 phosphatase

Front 24

Why can't muscles undergo gluconeogenesis?

Back 24

They don't have glucose-6 phosphatase (required to dephosphorylate G6P to yield glucose).

Hint 24

Yoooo

Front 25

Which pathways lead to gluconeogenesis?

Back 25

1. Odd chain FAs --> propionyl coA --> pyruvate --> gluconeogenesis

2. Krebs cycle molecules --> gluconeogenesis

3. Molecules --> OAA --> gluconeogenesis

4. AA --> TCA substrate, OAA, pyruvate

Hint 25

Many things can enter into the gluconeogenesis pathway.

Front 26

Can muscles generate glucose from glycogenolysis?

Back 26

No, they lack the ENZ glucose-6-phosphatase (the same ENZ required to complete gluconeogenesis), so the G6P they generate directly enters glycolysis.

Hint 26

Muscles never share Energy!

Front 27

Glycogen storage diseases: Name them and tell me why! (x4)

Back 27

1. Von Gierke's disease (Type 1)
- G6 Phosphatase deficiency.
Can't get free glucose from cell, can't share glucose from liver, kidneys. Severe fasting hypoglycemia, TONS of glycogen in liver, increased blood lactate levels (cells are starved for energy), increased uric acid (lactic acid/uric acid compete for excretion), and hepatomegaly (cells are swollen).

2. Pompe's disease (Type II)
- deficiency of lysosomal alpha1,4 glucosidase
Can't break alpha-1,4 glycosidic bonds.
Infantile and adult forms. (deets on hint)

3. Cori's disease (Type III)
- deficiency of debranching ENZ (alpha-1,6 glucosidase)
milder Type I (von Gierke's) with normal blood lactate levels.

4. McArdle's disease (Type V)
- deficiency of skeletal muscle glycogen phosphorylase.
Glycogen accumulates in muscle, but can't break it down. Draws in H20, cells swell and some lyse. Painful muscle cramps, myoglobinuria with strenuous exercise. (myoglobin in serum --> myoglobinuria --> clogs kidneys and causes Rhabdomyolysis).

Hint 27

Very Poor CHO Metabolism

Von Gierke's: Auto recessive.

Pompe's trashes the Pump. Auto recessive.

Cori's: Auto recessive. Gluconeogenesis is intact.

McArdle's: Auto recessive. McArdle's = Muscles.

Front 28

Glycogen phosphorylase deficiency

Back 28

McArdle's (V)

Front 29

Glucose-6-phosphatase deficiency

Back 29

Von Gierke's disease (I)

Front 30

Lactic acidosis, hyperlipidemia, hyperuricemia (Gout)

Back 30

Von Gierke's disease (I)

Front 31

Alpha 1,6 glucosidase deficiency

Back 31

Cori's disease (III)

Front 32

alpha 1,4 glucosidase deficiency

Back 32

Pompe's disease (II)

Hint 32

Very Poor CHO Metabolism

Front 33

Cardiomegaly (in a glycogen storage disorder)

Back 33

Pompe's (II) - infantile variant (early death)

Hint 33

Pompe's trashes the Pump (heart, liver, muscle)

Very Poor CHO Metabolism

Front 34

Diaphragm weakness leading to respiratory failure (in a glycogen storage disease)

Back 34

Pompe's (II) - Adult variant

Hint 34

Pompe's trashes the pump (heart, liver, muscle)

Very Poor CHO Metabolism

Front 35

Increased glycogen in liver, severe fasting hypoglycemia (glycogen storage disease)

Back 35

Von Gierke's (I)

Front 36

Hepatomegaly, hypoglycemia, hyperlipidemia (normal kidneys, lactic, and uric acid)

Back 36

Cori's disease (III)

Front 37

Painful muscle cramps, myoglobinuria with strenuous exercise

Back 37

McArdle's (V)

Front 38

Severe HSM, enlarged kidneys

Back 38

Von Gierke's disease (I)

Front 39

Co-factors required for PDH (pyruvate DH) complex:

Back 39

1. Thiamine (B1) --> TPP
2. Lipoic acid
3. CoA (B5, panthothenate)
4. FAD (B2, riboflavin)
5. NAD (B3, Niacin)

Hint 39

Tender Loving Care For No one

Front 40

Fates of pyruvate:

Back 40

1. Oxaloacetate via Pyruvate carboxylase (to TCA cycle or gluconeogenesis)

2. Acetyl co-A via PDH (pyruvate DH) from glycolysis to TCA cycle

3. Lactate via Lactic acid DH to anaerobic glycolysis Cori cycle (RBC, leukocytes, kidney medulla, lens, testes, cornea)

4. Alanine via Alanine aminotransferase (B6) to carry amino groups to liver.

Hint 40

APPL

Front 41

Which enzyme does Arsenic interfere with? What are the sx of exposure?

Back 41

Arsenic inhibits lipoic acid, which interferes with the functioning of Pyruvate DH complex.

Sx: vomiting, rice-water stools, and garlic breath. Looks like gastroenteritis with garlic breath.

Front 42

Key enzymes in TCA cycle:

Back 42

1. Citrate synthase
2. Isocitrate DH
3. alpha-KG DH

Produces 3NADH, 1FADH2, 2CO2, 1GTP per acetyl-coA = 10ATP/acetyl coA = 20ATP/glucose.

Hint 42

Occurs in mitochondria.

Front 43

Cofactors required for alpha-KG DH complex:

Back 43

Same cofactors as for pyruvate DH complex of last committing step of glycolysis:

Thiamine (B1) --> TPP
Lipoic acid
CoA (B5, pantothenate)
FAD (B2, riboflavin)
NAD (B3, niacin)

Hint 43

Tender Loving Care For No one

Arsenic inhibits lipoic acid.

Front 44

Pyruvate DH deficiency:

Back 44

causes backup of substrate (pyruvate and alanine) --> lactic acidosis.

Causes:
1. X linked mut of E1-alpha subunit of PDHC
2. Acquired (arsenic exposure, Vit B1, B2, B3, B5 deficiency).

Findings: Neurologic deficits, usually starting in infancy.

Rx: increase intake of ketogenic nutrients (high fat content OR high lysine/leucine)

Hint 44

Lysine and Leucine are the onLy pureLy ketogenic amino acids.

Front 45

Describe the 5 complexes of the ETC?

Back 45

Complex 1 - accepts electrons from NADH, moves H+.

Complex 2 (succinate DH) - accepts electrons from FADH2, moves H+. Passes electrons to CoQ.

Complex 3 - receives electrons from Complexes 1 and 2. Passes them via cytochrome c to Complex 4.

Complex 4 - passes electrons to final electron acceptor, O2 --> H2O. Moves H+.

Complex V - ATPase --> makes ATP using the energy from H+ gradient.

Front 46

Name the electron transport inhibitors:

Back 46

Complex 1 - inhibited by Rotenone, Amytal (barbituate) and MTP (from MPTP, which is what you make by accident if you're trying to home brew demerol or riperidine). [electron transport inhibitor]

Complex 2 - Nothing.

Complex 3 - Antimycin A [electron transport inhibitor]

Complex 4 - CN, CO, N3- (sodium azide), and H2S (hydrogen sulfide). [electron transport inhibitors]

Directly inhibit electron transport, causing decreased proton gradient and blocked ATP synthesis.

Hint 46

RAM A CONCH, OH!

Front 47

Name the ATP synthase inhibitor:

Back 47

Complex 5 - Oligomycin (ATP synthase inhibitor).

Directly inhibit ATPase, causing increased H+ gradient. No ATP produced because electron transport stops.

Hint 47

RAM A CONCH, OH!

Front 48

Name the uncoupling agents:

Back 48

2,4-DNP, ASA, thermogenin.

increase permeability of membrane, causing decreased proton gradient and increased O2 consumption. ATP synthesis stops, but electron transport continues.

Hint 48

DaT ASS is full of (brown) fat!

Front 49

Name the irreversible ENZ in gluconeogenesis:

Back 49

1. Pyruvate carboxylase (pyruvate--> OAA)
---requires biotin, ATP.
---activated by acetyl coA

2. PEP carboxykinase (OAA --> PEP)
---requires GTP

3. F16BPase (F16BP-->F6P)

G6Pase (G6P --> glucose)

Hint 49

Pathway Produces Fresh Glucose

Front 50

What is the deficiency in essential fructosuria?

Back 50

Fructokinase

Benign, as fructose isn't trapped in cells.

Sx: fructose appears in blood and urine.

Hint 50

Fructose appears in urine/blood.

Front 51

What is the deficiency in Fructose intolerance?

Back 51

Aldolase B

F1P accumulates, causing a decrease in available phosphate. Inhibits gluconeogenesis and glycogenolysis.

Sx: hypoglycemia, jaundice, cirrhosis, vomiting, hemorrhage.

rx: decrease intake of both fructose and sucrose (glucose+fructose).

Hint 51

F1P accumulates in cells.

FAB GUT.

Front 52

What results from a deficiency of galactokinase?

Back 52

Galactokinase deficiency.

Galactitol accumulates if galactose is present in diet. Mild.

Sx: galactose in urine/blood, infantile cataracts. May initially present as failure to track objects or failure to develop a social smile.

Hint 52

Accumulates in lenses.

Front 53

What results from a deficiency of galactose-1P uridyl transferase?

Back 53

Classic galactosemia.

Auto recessive.

Accumulation of toxic substances (like galactitol), which accumulates in lens of eye.

Sx: failure to thrive, jaundice, hepatomegaly, infantile cataracts, MR (builds up in neural tissues).

Hint 53

FAB GUT

Fructose is to Aldolase B as Galactose is to UridylTransferase

Front 54

Which are the important enzymes in the oxidative burst pathway?

Back 54

1. NADPH oxidase
(O2-->O2-.)

2. Superoxide dismutase
(O2-. --> H2O2)

3. Myeloperoxidase
(H2O2 +Cl --> HOCl.)

Front 55

What is the defiency in CGD?

Back 55

Chronic granulomatous disease:

NADPH deficiency (can't convert O2-->O2-.)

Phagolysosomes can't make caustic substances to digest bact.

Macrophages can make H2O2 from Env and use that to digest bacteria.

Bacteria with catalse can digest that H2O2, so phagocytes can't use it to digest bacteria.

Front 56

Draw the Lipid transport system:

Back 56

Note the deficiencies.

Front 57

Name the essential amino acids:

Back 57

Phenylalanine
Valine
Threonine

Tryptophan
Isoleucine
Methionine

Histidine
Leucine
Lysine

Hint 57

PVT TIM HaLL

Front 58

Name the acidic amino acidS:

Back 58

Aspartate and Glutamate (aspartic acid and glutamic acid)

Hint 58

GA! acid!

Front 59

Name the basic Amino Acids:

Back 59

Arginine, Lysine, Histidine

Arginine is most basic
Histidine has no charge at body pH

Hint 59

HAL is so basic.

Front 60

Which two amino acids are required during times of growth?

Back 60

Arg and His

Hint 60

Growing up, hahaha

Front 61

Which two amino acids are in high concentrations in histones?

Back 61

Arg and Lys

Hint 61

DNA's song - lalalalala

Front 62

AA derivatives of Phenylalanine?

Back 62

--> tyrosine (+BH4) via phenylalanine hydroxylase (missing in PKU)

--> DA (+BH4) via DA hydroxylase - inhibited by carbidopa

--> Dopamine (+Vit B6) via DA decarboxylase
- breakdown product: HVA

--> NE (+Vit C)
- Breakdown product: VMA

--> Epi (+SAM) - ramped up by cortisol
- Breakdown product: Metanephrine

Hint 62

Pheeny's That Damn Dope who Needs Everything.

Front 63

AA derivatives of Tryptophan?

Back 63

Niacin (+B6) --> NAD+/NADH

Serotonin (+BH4) --> Melatonin (pineal gland)

Hint 63

Tripping NiSe....energy and then sleep

Front 64

AA derivatives of Histidine?

Back 64

Histamine (+B6)

Hint 64

HH Gregg.

Front 65

AA derivatives of Glycine?

Back 65

-->porphyrin (+B6)

--> Heme (RLS aminolevulinic synthase)

Hint 65

Glycines pH

Front 66

AA derivatives of Glutamate?

Back 66

--> GABA (B6) - inhibitory NT

--> Glutathione - reducing agent

Hint 66

Glutes - All Gab, no gluttony.

Front 67

AA derivatives of Arginine?

Back 67

--> Creatitine (high E Phosphate carrier to supply ADP)

--> Urea

--> NO (vasodilator/smooth muscle relaxer)

Hint 67

Arghhh, ye mateys!! Create ur NOses now!

Front 68

Which is the most common type of urea cycle enzyme deficiency?

Back 68

Ornithine transcarbamoylase

Sx. of hyperammonemia:
- slurring speech
somnolence
vomiting
cerebral edema
blurred vision
(aka hepatoencephalopathy)

XLR

xs carbamoyl phosphate --> orotic acid

Findings: increased orotic acid in urine, DECREASED BUN (can't release nitrogen), and sx of hyperammonemia.

Front 69

What is the RLS of the urea cycle?

Back 69

CPS1 - converts NH4+ CO2 --> carbamoyl phosphate, using 2ATP

Front 70

Sx of hepatoencepalopathy, and how it arises?

Back 70

SX:
Slurred speech, somnolence, vomiting, cerebral edema, blurred vision

Arises:
acquired (liver dz)
hereditary (urea cycle ENZ deficiencies, e.g. ornithine transcarbamoylase def)

Hint 70

If you've got too much ammonia, you're slurring your vomit while sleepy, with blurry vision and a h/a.

Front 71

Rx for hepatoencephalopathy?

Back 71

Bind AA so it can be excreted:
Phenylbutyrate
Benzoate

Acidify GI tract/trap NH4+ for excretion:
Lactulose

Hint 71

Trap PB, Acid milk.

Front 72

Deficiency in PKU?

Back 72

Decreased phenylalanine hydroxylase OR BH4 (Phe --> tyr), so tyrosine becomes essential. Increased [phenylalanine] --> phenylketones in urine.

Phenylketones: phenylacetate, phenyllactate, phenylpyruvate.

Findings: MR, growth retardation, seizures, fair skin, eczema, musty body odor.

Rx: decrease Phe, supplement Tyrosine or BH4 within 2-3 wks of birth.

AR, 1/10,000. Screen 2-3 days after birth b/c maternal tyrosine has worn off and phenylketones are now detectable.

Hint 72

Disorder of Aromatic AA metabolism --> Musty BO

Front 73

Deficiency in Alkaptonuria?

Back 73

Homogentisic acid oxidase (degradative pathway of tyrosine to fumarate.

AR, benign.

Findings: dark CT, brown pigmented sclera, urine tyrnes black on prolonged exposure to air. May have debilitating arthralgias.

Presents in adulthood.

Front 74

Deficiency in Albinism?

Back 74

1. Tyrosinase (inability to synth melanin from tyrosine)

2. Defective tyrosine transporters (decr amt of tyrosine, thus decr melanin)

3. lack of migration of neural crest (melanocytes).

increased risk of skin cancer, variable inheritance.

Front 75

Deficiency in homocystinuria?

Back 75

1. cystathionine enthuse (rx by decreasing methionine and cystine, and increasing B12 and folate in diet)

2. decreased affinity of cystathione synthase for pyridoxal phosphate (rx increase amt B6 in diet)

3. homocysteine methyltransferase (requires B12) def

all result in xs homocysteine, and cysteine becomes essential.

Findings: increased homocystein in urine, MR, osteoporosis, tall stature, kyphosis, lens subluxation, and atherosclerosis.

Front 76

Deficiency in cystinuria?

Back 76

Defect in COLA transporter
- Cysteine
- Ornithine
- Lysine
- Arginine
PCT of the nephron.

Xs cystine --> precipitation of hexagonal crystals and renal staghorn calculi

AR, common (1,7000)

Rx: hydration and urinary alkalinization (Acetazolamide) - carbonic anhydrase inhibitor, alkalinizes urine to prevent stones.

Hint 76

cystine COLA

Front 77

Deficiency in maple syrup urine disease?

Back 77

Blocked degradation of BRANCHED AA (Ile, Leu, Val) d/t decreased branched alpha ketoacid DH (B1) complexes. Causes increased alpha keto acids in urine, esp Leucine.

Pres: severe CNS defects, MR, death.

Urine smells like maple syrup.

Hint 77

I Love Vermont MAPLE SYRUP from BRANCHED maple trees.

Front 78

Deficiency in Hartnup disease??

Back 78

AR
defective neutral AA transporter (tyrosine) on renal and intestinal epithelial cells.

CDauses tryp excretion in urne and decreased absorption in gut. Leads to PELLAGRA, cerebellar ataxia, aminoaciduria.

Blue diaper syndrome

3 Ds - Dermatitis, Diarrhea, Dementia.

Front 79

What are the sx of Pellagra?

Back 79

3Ds -
Diarrhea
Dementia
Dermatitis
(Death)

Front 80

Which substrates are required to synthesize purines?

Back 80

Glycine, Aspartate, Glutamine, THF, and CO2

Hint 80

GAG + COTH

Front 81

Which substrates are required for pyramidine synthesis?

Back 81

Glutamine, Aspartate, THF, CO2

Hint 81

GA + Coth

Front 82

Which is the RLS of purine synthesis?

Back 82

Glutamine PRPP amidotransferase (between PRPP and IMP).

Inhibited by 6-Mercaptopurine.

Front 83

Which step of de novo purine or pyramidine synthesis is inhibited by hydroxyurea?

Back 83

De novo pyramidine synthesis:

Inhibits ribonucleotide eductase, which converts UDP to dUDP.

Front 84

Which step of de novo purine or pyramidine synthesis does 5-FU inhibit?

Back 84

De novo pyramidine synthesis.

Inhibits Thymidylate synthase (converts dUMP --> dTMP)

Requires THF, which cycles using Dihydrofolate reductase to be regenerated.

Front 85

Which step of de novo purine or pyramidine synthesis does MTX inhibit? For whom?

Back 85

De novo pyramidine synthesis.

DHFR (converts DHF --> THF to be reused as a cofactor for thymidylate synthase (converts dUMP --> dTMP).

For eukaryotes. Used as anti-cancer or immunosuppressant in rheumatic disease.

Front 86

Which step of de novo purine or pyramidine synthesis does 6-MP inhibit?

Back 86

Purine synthesis.

Inhibits RLS - glutamien PRPP amidotransferase.

prevents de novo purine synthesis.

Front 87

What happens in an Ornithine Transcarbamoylase deficiency?

Back 87

Key enzyme in the urea cycle.


Leads to accumulation of carbamoyl phosphate, which is then converted to orotic acid. With a urea cycle enz deficiency, you have hyperammonemia AND orotic aciduria.

Front 88

What happens in orotic aciduria?

Back 88

Defect in UMP synthase of de novo pyramidine synthesis pathway. Cannot convert orotic acid to UMP.

Get increased orotic acid in urine, NO hyperammonemia (vs. OTC deficiency), megaloblastic anemia that DN improve with B12 or folate administration (because problem isn't with THF), failure to thrive.

Rx: oral uridine administration.

Front 89

What is the MOA of etoposide and fluoroquinolones?

Back 89

Inhibit eukaryotic and prokaryotic topoisomerase, respectively.

Front 90

What is Anti-scl70 targeting, what dz is it associated with?

Back 90

Targets topoisomerase.

A/w diffuse scleroderma.

Front 91

What is defective in xeroderma pigmentosum? What are the clinical manifestations?

Back 91

Defective nucleotide excision repair.

Prevents repair of thymidine dimers d/t UV light exposure.

Dry skin, melanoma, hypersensitivity to UV light, moreso than albinism. 1,000 fold increased risk of skin cancer.

Front 92

What is defective in HNPCC (hereditary nonpolyposis colorectal cancer)? What are the clinical manifestations?

Back 92

Mutated mismatch repair. increased risk of colon cancer.

Front 93

What is defective in Ataxia telangiectasia?

Back 93

Mutated non-homologous end joining in DNA synthesis/repair.

Sensitivity to ionizing radiation.
Cerebellar ataxia, onset 1-2y/o.
Telangiectasia, onset 5y/o.
Poor smooth pursuit.
immunodeficiency associated.
Increased alpha-FP in kids >8months old.

Front 94

What is defective in Bloom syndrome? What are the clinical manifestations?

Back 94

DNA helicase defect.

Hypersensitivity to light, leukemias, lymphomas, cancer onset at age 25, average.

AR, askenazi jews. Biutterfly scaly rash (nose/cheeks), telangiectasias, cafe au lait spots, immunodeficiency.

Front 95

What is deficient in BRCA1/BRCA2 mutation? What are the clinical manifestations?

Back 95

Defective repair of DS DNA breaks.

Increased risk of breast/ovarian cancer, specifically.