Biochem Clinical Cases And Rate Limiting Steps

Front 1

Glycolysis Rate Limit

Back 1

PFK-1

Front 2

Gluconeogenesis Rate Limit

Back 2

Fructose-1,6-Bisphosphatase

Front 3

TCA Cycle Rate Limit

Back 3

Isocitrate DH

Front 4

GLycogen Synth Rate Limit

Back 4

Glycogen SYnthase

Front 5

Glycogenolysis Rate Limit

Back 5

Glycogen Phosphorylase

Front 6

HMP Shunt Rate Limit

Back 6

G6PD

Front 7

Pyrimidine Synth Rate Limit

Back 7

Carbomyl Phosphate Synthetase II

Front 8

Purine Synthesis Rate Limit

Back 8

GLutamine-PRPP Amidotransferase

Front 9

Urea Cycle Rate Limie

Back 9

Carbomoyl Phosphate Synthetase I

Front 10

Fatty Acid Synth Rate Limit

Back 10

Acetyl-CoA Carboxylase

Front 11

Fatty Acid Oxidation Rate Limit

Back 11

Carnitine Acyltransferase I

Front 12

Ketogenesis Rate Limit

Back 12

HMG CoA Synthase

Front 13

Cholesterol Synth Rate Limit

Back 13

HMG CoA Reductase

Front 14

Pyr Kin Def

Back 14

no PEP --> Pyruvate

- Decrease ATP --> inhibit NaKATPase --> cell swelling and lysing
- Hemolytic Anemia --> Bilirubin

Front 15

Pyr DH Complex Deficiency

Back 15

-No Pyruvate to Acetyl-CoA
- Acquired: Cofactor Deficiency (TLC For No one)
Thiamine / B1 / TPP (Alcoholics)
Lipoic Acid (Arsenic Poisoning)
CoA / B5 / Pentothenate
FAD / B2 / Riboflavin
NAD / B3 / Niacin
- Congenital: X linked gene for E1-a PDC subunit
- Symptoms: Lactic Acidosis from pyruvate and Alanine back up, Neuro defects
- Tx: Lysine and Leucine - ketogenic amino acids

Front 16

Sx: Neurologic defects, Lactic Acidosis with Pyruvate backup

What's the cause? What's the treatment?

Back 16

Cause: Pyruvate DH Complex Def (Congenital X linked or Acquired Thiamine def)
Tx: Lysine and Leucine ketogenic Amino Acids, High fat content diet

Front 17

Sx: Poor feeding, Vomiting, Hypotonia, Seizures, Lethargy, Anion Gap acidosis, Propionyl CoA in urine

What's the cause? What's the treatment?

Back 17

Propionic Aciduria:
- Aut Recessive
- Can't convert Propionyl CoA to Methylmalonyl CoA (which then is converted to Succinyl CoA for TCA cycle)
- Tx: Decrease precursors of Propionyl CoA - Branch Chain Amino Acids Valine and Isoleucine, Theonine, Methionine, Odd Chain FAs

Front 18

Sx: Catalase positive organism infections S. Aureus and Aspergillus

What's the cause?

Back 18

Chronic Granulomatous Disease:
- NADPH Oxidase Deficiency - can't form reactive oxygen intermediates to destroy bacteria in the phagolysosome

Front 19

Sx: Hemolytic anemia in African American male after starting a new med, Heinz bodies, Bite cells

What's the cause?

Back 19

G6PD Deficiency:
- X linked
- Can't regenerate NADPH to reduce Glutathione to protect RBCs from free radical damage
- Triggers: Fava beans, Sulfonamides, Primaquine, TB drugs

Front 20

Sx: Healthy person with fructose in blood and urine

What's the cause?

Back 20

Essential Dructosuria:
- Fructokinase deficiency (KINDase - benign disease is kind to you)
- Able to use hexokinase to metabolize fructose for glycolysis instead of Fructokinase, an alternative metabolism not used in people without the deficiency

Front 21

Sx: Fasting Hypoglycemia, Jaundice, Cirrhosis, Vomiting. Problem with fructose metabolism.

What's the cause? What's the treatment?

Back 21

Fructose Intolerance:
- Aldolase B deficiency (B for Bad)
- Fructose-1-P accumulates, which uses up all the phosphate so there isn't any for Glycogenolysis or Gluconeogenesis, causing fasting hypoglycemia.
- Treatment; Decrease Fructose and Sucrose

Front 22

Sx: Galactose in Blood and Urine, Cataracts, otherwise asymptomatic.

What's the cause?

Back 22

- Galactokinase deficiency (KINDase - benign)
- Galactose --Aldose Reductase --> Galactitol --> cataracts

Front 23

Sx: Failure to Thrive, Jaundice, Hepatomegaly, Infantile Cataracts, Mental retardation.

What's the cause? What's the treatment?

Back 23

Classic Galactosemia:
- Glactose-1-Phosphate Uridyltransferase Deficiency (UDP-Gal
- Aut Recessive
- Galactose --> Galactitol via Aldose Reductase forms cataracts
- Treatment: Exclude Galactose and Lactose form diet

Front 24

Sx: Diabetes Type 2, Cataracts, Retinopathy, Peripheral Neuropathy

What's the cause?

Back 24

Sorbitol
- Glucose -- Aldose Reductase --> Sorbitol --> osmole that draws in water causing osmotic damage
- Schwann cells, Retina, and Kidneys do not have Sorbitol DH and can't convert Sorbitol to Fructose, so Sorbitol builds up with high glucose

Front 25

Sx: Hyperammonemia, Tremor, Slurred speech, somnolence, Vomit, Cerebral edema, Blurred vision, Orotic Acid in blood and urine, Decreased BUN

What causes it? What's the treatment?

Back 25

Cause:
- Acquired: Liver disease (impaired urea cycle)
- X Linked: Ornithine Transcarbamoylase deficiency
- Pathophysiology: Excess NH4+ --> Deplete a-KG --> Inhibit TCA
Treatment:
- Lactulose: Gut bacteria eat up the sugar --> Acidify GI tract --> Trap NH4+ --> Excrete it in stool
- Phenylbutyrate / Benzoate: Bind amino acid for excretion?
- Decrease Protein in Diet!

Front 26

Phenylalanine --> ?

Back 26

Tyrosine --> Thyroxine
Dopa --> Melanin
Dopamine
NE
Epi

Front 27

Tryptophan --> ?

Back 27

Niacin/ B3 / NAD/NADP (w B6)
Serotonin --> Melatonin

Front 28

Histidine --> ?

Back 28

Histamine (w B6)

Front 29

Glycine --> ?

Back 29

(w B6) Porphyrin --> Heme

Front 30

Arginine --> ?

Back 30

Creatine
Urea
Nitric Oxide

Front 31

Glutamate -->

Back 31

GABA (w B6)
Glutathione

Front 32

Sx: Mental retardation, Growth retardation, Seizures, Fair skin, Eczema, Musty Body Odor, Phenylketones in urine

What's the cause? What's the treatment?

Back 32

PKU:
- Deficiency in Phenylalanine Hydroxylase or BH4 Cofactor (tetrahydrobiopterin)
- Treatment: TYROSINE is an essential for Dop, NE, and Epi synth. Decrease Phenylalanine.

Front 33

Sx: Dark connective tissue, Brown pigmented sclera, Urine turns black on prolonged exposure to air, relatively benign disease, +/- arthralgias

What's the cause?

Back 33

Alkaptonuria / Ochronosis:
- Homogentistic Acid Oxidase deficiency
- Homogentisic Acid builds up in Tyrosine's degredative pathway to Fumarate
- Aut Recessive

Front 34

Sx: PKU treated with Tyrosine, but there is still low Dopamine levels

What's the cause?

Back 34

Dihydropteridine Reductase Deficiency
- Used to convert Phenylalanine to Tyrosine AND Tyrosine to Dopa
- Still not able to convert Tyrosine to Dopa!

Front 35

Albinism

What are the cuases?

Back 35

- Deficiency of either Tyrosinase
- Defective Tyrosine Transporters
- Lack of migration of neural crest cells --> Absent melanocytes

Front 36

Sx: marfanoid body, Homocysteine in urine, mental retardation, osteoporosis, kyphosis, lens subluxation down and in, atherosclerosis

What are the causes? What becomes an essential amino acid?

Back 36

Homocysteinuria:

CYSTEINE is essential

1) Cystathionine Synthase Deficiency: Can't convert Homocysteine to Cystathionine. Requires B6.
Treat: Increase Cysteine, B12, and Folate in diet, Decrease Methionine

2) Cystathionine Synthase lose affinity for B6: Can't convert Homocystein to Cystathionine.
Treat: Increase B6 in diet

3) Homocystein Methyltransferase Deficiency: Can't convert Methionine to Homocysteine.

Front 37

Sx: Systeinuria, Staghorn calculi

What's the cause? What's the treatment?

Back 37

- Defect in kidney PCT amino acid transporter for COLA: Cysteine, Ornithine, Lysine, and Arginine
- Treatment: Hydration, Alkalinization of urine with Acetyl Solamide

Front 38

Sx: Urine smells like maple syrup, CNS defects, mental retardation

What's the cause?

Back 38

- a-Ketoacid Dehydrogenase deficiency (note: this enzyme also requires TLC For No one)
- Can't degrade branched amino acids Ile, Leu, and Val
- a-Ketoacids build up in blood

Front 39

Sx: Dermatitis, Diarrhea, Dementia due to an absorption problem.

What's the cause?

Back 39

Hartnup disease:
- Defective amino acid transporter in renal and intestinal cells decreases tryptophan absorption
- Decrease Niacin/B3 synthesis, causing Pellagra

Front 40

Sx: Severe Fasting Hypoglycemia, Glycogen build up in liver, Lactic Acidosis, Hepatomegaly

What's the cause?

Back 40

Von Gierke's - Type 1 Glycogen Storage Disease
- Gluc-6-Phosphate Deficiency
- This is the last step in gluconeogenesis AND the last step in glygogenolysis from G-6-P to Glucose, so both are impaired, leading to its seriousness

Front 41

Sx: Cardiomegaly in infants or Diaphragm weakness and respiratory failure in adults.

What's the cause?

Back 41

Pompe's - Type 2 Glycogen Storage Disease
- a-1,4-Glucosidase / Acid Maltase / acid a-glucosidase Deficiency (it's called different things in FA, World, NBME practice test)
- Impaired lysosomal degradation of glycogen to glucose. Glycogen accumulation in lysosomes.

Front 42

Sx: Hypoglycemia, Hepatosplenomegaly, dextrin like material built up in hepatocyte cytosol, NO lactate build up

What's the cause?

Back 42

Cori's - Type 3 Glycogen Storage Disease
-a-1,6-Glucosidase / Debranching Enzyme deficiency
- Problem with glucogenolysis, but gluconeogenesis works just fine, which is why the fasting hypoglycemia is just mild

Front 43

Sx: Glycogen build up in muscle, painful muscle cramps, myoglobinuria with exercise

What's the cause?

Back 43

McArdles's - Type 5 Glycogen Storage DIsease
- Glycogen Phosphorylase deficiency in skeletal muscle (can't break a 1,4)
- cells swell with glycogen and pull in water and lyse, raleasing myoglobin

Front 44

Sx: Peripheral Neuropathy of hands and feet, Angiokeratomas, CV and Renal disease

What's the name, deficiency, inheritance, and accumulated substrate?

Back 44

- Fabry's
- a-Galactosidase A
- Ceramid Substrate
- Xlinked

Front 45

Sx: HSM, aseptic necrosis of bones, crumpled tissue paper macrophages.

What's the name, deficiency, inheritance, and accumulated substrate?

Back 45

- Goucher's
- Glucocerebrosidase
- Glucocerebroside
- Aut Rec

Front 46

Sx: Neurodegeneration, HSM, CHerry red spot on macula, Foam cells

What's the name, deficiency, inheritance, and accumulated substrate?

Back 46

- Niemann Pick
- Sphingomyelinase
- Sphingomyelin
- Aut Rec

Front 47

Sx: Neurodegeneration, Dev delay, Cherry red spot on macula, onion skin lysosomes, NO HSM

What's the name, deficiency, inheritance, and accumulated substrate?

Back 47

- Tay Sachs
- Hexosaminidase A
- GM2 Ganglioside
- Aut Rec

Front 48

Sx: Peripheral neuropathy, dev delay, Optic atrophy, Globoid cells

What's the name, deficiency, inheritance, and accumulated substrate?

Back 48

- Krabbe's
- Galactocerebrosidase
- Galactocerebroside
- Aut Rec

Front 49

Sx: Demyelination, Ataxia, Dementia

What's the name, deficiency, inheritance, and accumulated substrate?

Back 49

- Metachromatic Leukodystrophy
- Arylsulfatase A
- Cerebroside Sulfate

Front 50

Sx: Dev delay, Corneal clouding, HSM, gargoylism, airway obstruction, NO aggressive behavior

What's the name, deficiency, inheritance, and accumulated substrate?

Back 50

- Hurler's
- a-L-iduronidase
- Heparan Sulfate and Dermatan Sulfate
- Aut Rec

Front 51

Sx: Mild dev delay and HSM and gargoylism, Aggressive behavior, No corneal clouding.

What's the name, deficiency, inheritance, and accumulated substrate?

Back 51

- Hunter's
- Iduronate Sulfatase
- Heparan sulfate and Dermatan sulfate
- X linked

Front 52

Sx: Weakness, Hypotonia, Hypoketotic hypoglycemia, toxic FA and TG accumulation in muscles, Myoglobinemia

What's the cause?

Back 52

Carnitine deficiency:
- unable to shuttle FA into the mitochondrial matrix for B-oxidation

Front 53

Sx: Increased Chylomicrons, TG, and Cholesterol in blood. Pancreatitis, Abdom pain, HSM, Xanthomas. No Atherosclerosis.

What's the cause?

Back 53

Type 1 Familial Dyslipidemia: Hyper-Chylomicronemia
- Aut Rec
- LPL deficiency or altered ApoCII

Front 54

Sx: Increased LDL and Cholesterol in blood. Accelerated Atherosclerosis, Xanthomas on achilles or eyelid, Corneal Arcus.

What's the cause?

Back 54

Type IIa Familial Dyslipidemia: Hyper-Cholesterolemia
- Aut Dom
- LDL Receptor deficiency
- Peripheral tissues can't take up the LDL out of circulation

Front 55

Sx: Pancreatitis, Abdom pain. High VLDL and TG in blood.

What's the cause?

Back 55

Type IV Familial Dyslipidemia: Hyper-Triglyceridemia
- Aut Dom
- Hepatic overproduction of VLDL

Front 56

Sx: Xanthomas, early peripheral vasc disease. Increased Cholesterol and TG levels in blood.

What's the cause?

Back 56

Type III Familial Dyslipidemia: Dys-Beta-Lipoproteinemia
(Not in First Aid but had a UWorld question)
- ApopE deficiency, Liver cells can't uptake chylomicron remnants from circulation

Front 57

Sx: Failure to thrive, Steatorrhea, Acanthocytosis (spikey RBCs), Ataxia, Night Blindness

What's the cause?

Back 57

Abetalipoproteinemia:
- Aut Rec
- Mutation in MTP gene (microsomal TG transfer protein)
- Decrease ApoB48: can't remove the chylomicroms from the intestinal enterocytes. Lipid accumulation in enterocytes.
- Decrease ApoB100: Peripheral tissues can't bind to LDL Receptor
- DEcrease chylomicron and VLDL synthesis and secretion
- Tx w Vit E to restore Lipoproteins

Front 58

Sx: Painful abdomen, Port wine urine, Polyneuropathy, Psych disturbances, Precipitated by drugs

What's the cause? What's the treatment?

Back 58

Acute Intermittent Porphyria:
- Porphobilinogen Deaminase deficiency
- Porphobilinogen, d-ALA, and Urporphyrin all build up
- Treat with Glucose and Heme --> Inhibit ALA SYnthase --> Decrease toxic build up

Front 59

Sx: Blistering cutaneaous photosensitivity, Tea colored urine, Hypertrichosis

What's the cause?

Back 59

Porphyria Cutanea Tarda:
- Urophorphyrinogen Decarboxylase deficiency
- Uroporphytin builds up

Front 60

Sx: Hypoketootic Hypoglycemia after fasting

Back 60

Acyl-CoA Dehydrogenase Deficiency:
- Can shuttle the FA into the mitochondrial matrix, but can't undergo B-oxidation to ketone bodies and TCA cycle.
- Differentiate from Carnitine deficiency (also hypoketonic hypoglycemia but also with weakness, hypotonia, myoglobinemia)

Front 61

Sx: Orotic acid in urine, Megaloblastic anemia. NO hyperammonemia.

Back 61

Orotic Aciduria
- UMP Synthase deficiency
- Inability to convert Orotic Acid to UMP in de novo pyrimidine synthesis
- Vit B12 and Folic Acid don't help the anemia
- Tx: Oral Uridine administration

- Differentiate from Ornithine Transcarbamoylase deficiency which also has hyperammonemia and is treated differently

Front 62

Sx: Self mutilating child (lip biting), aggression, retardation, hyperuricemia

Back 62

Lesch Nyan:
- Decrease HGPRT
- increase PRPP
- Tx: ALlopurinol to decrease uric acid

Front 63

Sx: Anion gap acidosis, ketosis, hypoglycemia, methylmalonic acid high in plasma and urine, lethargy, comitting tachypnea

Back 63

Methylmalonic Acidemia/Aciduria
- Defect in isomerization transforming methylmalonyl CoA to succinyl coA, preventing TCA cycle