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310 Cards in this Set
- Front
- Back
|
What is the rate controlling enzyme of the cholesterol metabolic pathway?
|
HMG-CoA Reductase
|
|
|
What is the target of the statin drugs?
|
HMG-CoA Reductase
|
|
|
What reaction is catalyzed by HMG-CoA Reductase?
|
HMG-CoA -> mevalonate/mevalonic acid
|
|
|
How do statins work?
|
They lower serum cholesterol by reducing de novo synthesis of cholesterol.
|
|
|
When is HMG-CoA active?
|
When blood glucose is high (insulin increases, glucagon decreases levels)
|
|
|
What is the rate controlling enzyme of the pentose phosphate pathway?
|
Glucose 6-P DH
|
|
|
What reaction is catalyzed by Glucose 6-P DH?
|
Glucose 6-P DH + NADP -> 6-Phosphogluconae + NADPH
|
|
|
What is the MCC of hemolytic anemia?
|
G6PD deficiency (RBCs contain Heinz bodies)
|
|
|
What is the genetic mechanism of G6PD deficiency?
|
X-linked Recessive
|
|
|
What can trigger a G6PD crisis and/or Steven Johnson syndrome?
|
Anything that induces oxidative stress (i.e. anti-malarial or sulfa drugs, fava beans, infection)
|
|
|
What is the purpose of the pentose phosphate pathway?
|
To produce NADPH and ribulose-5-phosphate, which is used for nucleotide synthesis.
|
|
|
What is NADPH used for?
|
Biosynthesis, maintenance of reduced glutathione (protection vs ROS) and bactericidal activity by PMNs.
|
|
|
What activates G6PD?
|
Insulin & NADP
|
|
|
What enzyme allows for conversion of extraneous 3-C product of beta oxid of odd-chain FAs to products which can be used in the TCA cycle?
|
Methylmalonate CoA Mutase
|
|
|
What reaction is catalyzed by Methylmalonate CoA Mutase?
|
Methylmalonyl CoA --> Succinyl CoA
|
|
|
What cofactor is required by methylmalonate CoA mutase?
|
B12!!!
|
|
|
If not corrected, what can B12 deficiency lead to?
|
Megaloblastic anemia & peripheral neuropathy (b/c abberant FA's are incorporated into myelin sheaths)
|
|
|
Excretion of what acid indicates B12 deficiency over folate deficiency?
|
Methylmalonic Acid
|
|
|
What is the role of UDP-Glucuronyltransferase?
|
Glucuronidation rxn (phase II – conjugation of non-soluble substances/drugs/bilirubin to prepare for excretion)
|
|
|
What reaction is catalyzed by UDP-Glucuronyltransferase?
|
Transfer of glucuronosyl group from uridine 5’-diphospho-glucuronic acid (UDPGA) to substrate molecules.
|
|
|
What enzyme deficiency leads to physiology jaundice?
|
At birth there are low levels of UDP-Glucuronyltransferase, which leads to phsyiologic jaundice (and kernicterus) if left unchecked.
|
|
|
What is the genetic mechanism of Crigler-Najjar syndrome?
|
Autosomal Recessive
|
|
|
What enzyme is deficienct in Crigler-Najjar syndrome?
|
UDP-Glucuronyltransferase
|
|
|
What is the result of an absence of UDP-Glucuronyltransferase?
|
Crigler-Najjar syndrome -> Extreme jaundice in newborns
|
|
|
How do you treat Crigler-Najjar syndrome?
|
Phototherapy, exchange transfusions, heme oxygenase inhibitors, and liver transplant
|
|
|
What is Gilbert syndrome?
|
Reduced UDP-Glucuronyltransferase activity leading to mild elevation of unconjugated bilirubin during times of stress
|
|
|
What is the genetic mechanism of Gilbert syndrome?
|
Autosomal Recessive
|
|
|
What enzyme allows for conversion of homocysteine to S-adenosylmethionine (SAM)?
|
Homocysteine Methyltransferase
|
|
|
Why is 5-adenosylmethionine (SAM) important?
|
It is an important molecule that donates methyl groups (required for purine, thymidine, epinephrine and mRNA sythesis)
|
|
|
What reaction is catalyzed by Homocysteine Methyltransferase?
|
Homocysteine -> Methionine
|
|
|
What cofactors are required by Homocysteine Methyltransferase?
|
B12 & Folic Acid
|
|
|
What does homocysteine methyltransferase deficiency cause?
|
Homocysteinuria (rare) -> ↑ oxidation of LDL particles -> dislocated lenses, DVT, stroke, atherosclerosis (in kids), mental retardation, MI <20yo
|
|
|
What is the MCC of homocysteinuria?
|
Vitamin Deficiency (B12, B6, Folic Acid)
|
|
|
What is the most important enzyme in de novo pyrimidine synthesis?
|
Dihydrofolate Reductase
|
|
|
What reaction is catalyzed by dihydrofolate reductase?
|
Dihydrofolate -> Tetrafolate
|
|
|
What drugs target dihydrofolate reductase?
|
Methotrexate (antineoplastic, eukaryotic S phase), Trimethoprim (antibiotic, prokaryotic), & Pryimethamine (antiprotozoal)
|
|
|
What is the rate controlling enzyme of the cholesterol metabolic pathway?
|
HMG-CoA Reductase
|
|
|
What is the target of the statin drugs?
|
HMG-CoA Reductase
|
|
|
What reaction is catalyzed by HMG-CoA Reductase?
|
HMG-CoA -> mevalonate/mevalonic acid
|
|
|
How do statins work?
|
They lower serum cholesterol by reducing de novo synthesis of cholesterol.
|
|
|
When is HMG-CoA active?
|
When blood glucose is high (insulin increases, glucagon decreases levels)
|
|
|
What is the rate controlling enzyme of the pentose phosphate pathway?
|
Glucose 6-P DH
|
|
|
What reaction is catalyzed by Glucose 6-P DH?
|
Glucose 6-P DH + NADP -> 6-Phosphogluconae + NADPH
|
|
|
What is the MCC of hemolytic anemia?
|
G6PD deficiency (RBCs contain Heinz bodies)
|
|
|
What is the genetic mechanism of G6PD deficiency?
|
X-linked Recessive
|
|
|
What can trigger a G6PD crisis and/or Steven Johnson syndrome?
|
Anything that induces oxidative stress (i.e. anti-malarial or sulfa drugs, fava beans, infection)
|
|
|
What is the purpose of the pentose phosphate pathway?
|
To produce NADPH and ribulose-5-phosphate, which is used for nucleotide synthesis.
|
|
|
What is NADPH used for?
|
Biosynthesis, maintenance of reduced glutathione (protection vs ROS) and bactericidal activity by PMNs.
|
|
|
What activates G6PD?
|
Insulin & NADP
|
|
|
What enzyme allows for conversion of extraneous 3-C product of beta oxid of odd-chain FAs to products which can be used in the TCA cycle?
|
Methylmalonate CoA Mutase
|
|
|
What reaction is catalyzed by Methylmalonate CoA Mutase?
|
Methylmalonyl CoA --> Succinyl CoA
|
|
|
What cofactor is required by methylmalonate CoA mutase?
|
B12!!!
|
|
|
If not corrected, what can B12 deficiency lead to?
|
Megaloblastic anemia & peripheral neuropathy (b/c abberant FA's are incorporated into myelin sheaths)
|
|
|
Excretion of what acid indicates B12 deficiency over folate deficiency?
|
Methylmalonic Acid
|
|
|
What is the role of UDP-Glucuronyltransferase?
|
Glucuronidation rxn (phase II – conjugation of non-soluble substances/drugs/bilirubin to prepare for excretion)
|
|
|
What reaction is catalyzed by UDP-Glucuronyltransferase?
|
Transfer of glucuronosyl group from uridine 5’-diphospho-glucuronic acid (UDPGA) to substrate molecules.
|
|
|
What enzyme deficiency leads to physiology jaundice?
|
At birth there are low levels of UDP-Glucuronyltransferase, which leads to phsyiologic jaundice (and kernicterus) if left unchecked.
|
|
|
What is the genetic mechanism of Crigler-Najjar syndrome?
|
Autosomal Recessive
|
|
|
What enzyme is deficienct in Crigler-Najjar syndrome?
|
UDP-Glucuronyltransferase
|
|
|
What is the result of an absence of UDP-Glucuronyltransferase?
|
Crigler-Najjar syndrome -> Extreme jaundice in newborns
|
|
|
How do you treat Crigler-Najjar syndrome?
|
Phototherapy, exchange transfusions, heme oxygenase inhibitors, and liver transplant
|
|
|
What is Gilbert syndrome?
|
Reduced UDP-Glucuronyltransferase activity leading to mild elevation of unconjugated bilirubin during times of stress
|
|
|
What is the genetic mechanism of Gilbert syndrome?
|
Autosomal Recessive
|
|
|
What enzyme allows for conversion of homocysteine to S-adenosylmethionine (SAM)?
|
Homocysteine Methyltransferase
|
|
|
Why is 5-adenosylmethionine (SAM) important?
|
It is an important molecule that donates methyl groups (required for purine, thymidine, epinephrine and mRNA sythesis)
|
|
|
What reaction is catalyzed by Homocysteine Methyltransferase?
|
Homocysteine -> Methionine
|
|
|
What cofactors are required by Homocysteine Methyltransferase?
|
B12 & Folic Acid
|
|
|
What does homocysteine methyltransferase deficiency cause?
|
Homocysteinuria (rare) -> ↑ oxidation of LDL particles -> dislocated lenses, DVT, stroke, atherosclerosis (in kids), mental retardation, MI <20yo
|
|
|
What is the MCC of homocysteinuria?
|
Vitamin Deficiency (B12, B6, Folic Acid)
|
|
|
What is the most important enzyme in de novo pyrimidine synthesis?
|
Dihydrofolate Reductase
|
|
|
What reaction is catalyzed by dihydrofolate reductase?
|
Dihydrofolate -> Tetrafolate
|
|
|
What drugs target dihydrofolate reductase?
|
Methotrexate (antineoplastic, eukaryotic S phase), Trimethoprim (antibiotic, prokaryotic), & Pryimethamine (antiprotozoal)
|
|
|
What enzyme salvages purines from degraded DNA to renewed purine synthesis?
|
HGPRT
|
|
|
What reacion is catalyzed by HGPRT?
|
Guanine + PRPP -> GMP
|
|
|
What drug is converted to its active form by HGPRT?
|
Allopurinol
|
|
|
What enzyme deficiency leads to Lesch-Nyhan syndrome?
|
HGPRT
|
|
|
What is the genetic mechanism of Lesch-Nyhan syndrome?
|
X-linked Recessive
|
|
|
What are the consequences of HGPRT deficiency?
|
Lesch-Nyhan syndrome -> hyperuricemia & hyperuricosuria -> mental retardation, spastic cerebral palsy w/ compulsive biting of hands & lips, death
|
|
|
What is a secondary consequence of HGPRT deficiency?
|
Poorly utilized B12 -> megaloblastic anemia
|
|
|
True/False - Both behavior and gout Sx of Lesch-Nyhan syndrome respond well to allopurinol.
|
False - Only the gout Sx of Lesch-Nyhan syndrome respond to allopurinol.
|
|
|
What enzyme allows for the degradation of the branched chain amino acids?
|
Branched Chain Ketoacid DH
|
|
|
What are the branched chain amino acids?
|
Val, Ile, Leu
|
|
|
What reaction is catalyzed by Branched Chain Ketoacid DH?
|
Val, Ile, Leu -> acetyl CoA or Propionyl CoA
|
|
|
What cofactors are required by Branched Chain Ketoacid DH?
|
Thiamine diphosphate, FAD, NAD, Lipoate, CoA
|
|
|
What enzyme deficiency leads to Maple Syrup Urine Disease?
|
Branched Chain Ketoacid DH (I Love Vermont)
|
|
|
What is the typical course of Maple Syrup Urine Disease?
|
Infants: 1-3 days = normal; 3+ days = progressive lethargy, wt loss, alternating hypertonia & hypotonia, characteristic maple syrup urine
|
|
|
What is the treatment for Maple Syrup Urine Disease?
|
Restriction of dietary Ile, Leu, Val
|
|
|
If not corrected, what can Maple Syrup Urine Disease lead to?
|
Ketosis, Coma, Death
|
|
|
What are the essential amino acids?
|
Ile, Leu, Lys, Met, Phe, Thr, Trp, Val, His* (PVT TIM HALL -> His is only essential in infants)
|
|
|
What are the nonessential amino acids?
|
Ala, Asp, Asn, Cys, Glu, Gln, Gly, Pro, Ser, Tyr, Arg)
|
|
|
What are the positively charged (acidic) amino acids?
|
Arg, His, Lys
|
|
|
What are the negatively charged (basic) amino acids?
|
Asp, Glu
|
|
|
What are the nonpolar amino acids?
|
Ala, Cys, Gly, Ile, Leu, Met, Phe, Pro, Trp, Val
|
|
|
What are the polar amino acids?
|
Arg, Asn, Asp, Glu, Gln, His, Lys, Ser, Thr, Tyr
|
|
|
What are the aromatic amino acids?
|
Phe, His, Tyr, Trp
|
|
|
What are the sulfur-containing amino acids?
|
Cys, Met
|
|
|
What enzyme aids Vit K in the formation of Ca2+ binding site on Ca2+-dependent proteins?
|
Vitamin K Decarboxylase (gamma-Glutanylcarboxylase)
|
|
|
What are the Ca-dependent proteins aided by Vitamin K Decarboylase?
|
II, VII, IX, X, protein C, protein S
|
|
|
What cofactor is required by gamma-Glutanylcarboxylase?
|
Vitamin K
|
|
|
What are the Sx of Vitamin K deficiency?
|
Prolonged bleeding, easy bruising, potentially fatal hemorrhagic disease
|
|
|
What conditions predispose to Vitamin K deficiency?
|
Fat malabsorption (Vit K is lipid-soluble), bile duct occlusion, prolonged Tx w/ broad spectrum antibiotics, breast-fed newborns (esp in home birth w/ no postnatal Vit K injection), mothers Tx w/ certain anticonvulsants (phenylhydantoins)
|
|
|
What drug indirectly inhibits the action of gamma-Glutanylcarboxylase (AKA Vitamin K Decarboxylase)?
|
Warfarin (through inhibition of Vitamin K recycling)
|
|
|
What enzyme catabolizes purines for excretion as urin acid?
|
Xanthine Oxidase
|
|
|
What reactions are catalyzed by Xanthine Oxidase?
|
Hypozanthine + H2O -> xanthine + H2O2 & Xanthine + H2O -> uric acid + H2O2
|
|
|
What drug inhibits the actions of Xanthine Oxidase?
|
Allopurinol
|
|
|
What is allopurinol used to treat?
|
Chronic Gout
|
|
|
What are the major characteristics of gout?
|
Hyperuricemia & needle-shaped crystals with negative bifringence upon microscopic evaluation of aspirated synovial fluid
|
|
|
What enzyme is involved in the hydrolysis of hexose-containing molecules (i.e. lipids & gangliosides)?
|
Hexosaminidase A
|
|
|
What is the result of an absence of Hexosaminidase A?
|
An inability to hydrolyze certain sphingolipids, causing accumulation of lipids within lysosomes
|
|
|
Tay-Sachs Disease is associated with a deficiency of what enzyme?
|
Hexosaminidase A
|
|
|
What is the genetic mechanism of Tay-Sachs disease?
|
Autosomal Recessive
|
|
|
What molecule is accumulated within lysosomes of patients with Tay-Sachs disease?
|
GM2 Gangliosides
|
|
|
What are gangliosides?
|
A glycosphginolipid + one or more sialic acids, commonly found in nervous tissue of the brain
|
|
|
What are the Sx of Tay-Sachs disease?
|
Cherry red spots in macula (normal macular surrounded by abnormal fatty tissue), blindness, psychomotor retardation, death <2yrs
|
|
|
Tay-Sachs Disease is associated with what population?
|
Ashkenazi Jews
|
|
|
Why is Tay-Sachs disease considered one of the most important medical breakthroughs?
|
The inexpensive enzyme assay discovered to test for Tay-Sachs was one of the first mass-screening tools developed for the field of medical genetics
|
|
|
What is Sandhoff disease?
|
Clinically undistinguishable from Tay-Sachs, Sandhoff disease is a defiency in hexosaminidase A & B leading to an accumulation of GM2 gangliosides within lysosomes
|
|
|
What is the genetic mechanism of Sandhoff disease?
|
Autosomal Recessive
|
|
|
What enzyme catalyzes the conversion of galactose into glucose?
|
Galactose-1-P-Uridyltransferase (GALT)
|
|
|
Deficiency of GALT leads to what clinical situation?
|
Galactosemia
|
|
|
What is Galactosemia?
|
Ingestion of milk by infants results in vomiting, lethargy, jaundice, hepatopathy, renal failure
|
|
|
What is the treatment for Galactosemia?
|
Lactose-free, galactose-reduced diet
|
|
|
If left untreated, what are the consequences of galactosemia?
|
Severe damage of kidneys, liver, lenses, mental retardation
|
|
|
What enzyme links the glycolysis metabolic pathway to the TCA cycle or FA biosynthesis?
|
Pyruvate DH
|
|
|
True/False - Pyruvate DH is an irreversible reaction.
|
TRUE
|
|
|
What cofactors are required by pyruvate DH?
|
Thiamine pyrophosphate (from thiamine), Lipoic acid, CoA, FADH2 (from riboflavin), NADH (from niacin) “Tender Loving Care For Nancy”
|
|
|
Deficiency of pyruvate DH leads to what clinical situation?
|
Lactic Acidosis
|
|
|
What types of patients are especially prone to deficiency of pyruvate DH?
|
Alcoholics - Due to chronic thiamine deficiency
|
|
|
How should you treat an alcoholic patient presenting to the ER with lactic acidosis?
|
Give thiamine first, then glucose replacement (prevents complete conversion to lactic acid & worsening of the overall condition)
|
|
|
What enzyme provides malonyl CoA substrate for the biosynthesis of FAs?
|
Acetyl CoA Carboxylase
|
|
|
What cofactors are required by Acetyl CoA Carboxylase?
|
Biotin, ATP, CO2
|
|
|
What is the rate-limiting step of FA biosynthesis?
|
Acetyl CoA Carboxylase
|
|
|
What activates Acetyl CoA Carboxylase?
|
Insulin & Citrate
|
|
|
What enzyme hydrolyzes triglycerides to FAs and glycerol?
|
Hormone Sensitive Lipase
|
|
|
When is Hormone Sensitive Lipase active?
|
Fasting States - decreased insulin, increased glucagon, increased Epi, increased Cortisol
|
|
|
Deficiency of Carbamoyl Phosphate Synthetase I leades to what clinical Sxs?
|
↑ [NH4], hyperammonemia, ↑glutamine, ↑BUN, NO increase in uracil or orotic acid, lethargy, convulsions, coma, death
|
|
|
Deficiency of Ornithine Transcarbamoylase leades to what clinical Sxs?
|
↑ [NH4], hyperammonemia, ↑glutamine, ↑BUN, YES increase in uracil or orotic acid, lethargy, convulsions, coma, death
|
|
|
How do you treat deficiencies of either Carbamoyl Phosphate Synthetase I or Ornithine Transcabamoylase?
|
Low protein diet, administration of sodium benzoate or phenylpyruvate to capture excess nitrogen
|
|
|
What is marasmus?
|
Deficiency of all types of vitamins & nutrients (AKA starving to death)
|
|
|
What is kwashiorkor?
|
Deficiency of protein, leading to ascites & fatty liver
|
|
|
What is the MCC of B6/PLP deficiency?
|
Isonazid (INH) Therapy
|
|
|
What is scurvy?
|
Poor wound healing, easy bruising, bleeding gums, anemia
|
|
|
What is the MCC of scurvy?
|
Vitamin C Deficiency (lack of citrus fruits & green veggies)
|
|
|
What are the antioxidant vitamins?
|
Vitamins A, C, E
|
|
|
Where is Vitamin A especially utilized?
|
The retina (important for rods & cones) & epithelium
|
|
|
What are the Sx of Niacin (B3) deficiency?
|
Pellagra (diarrhea, dementia, dermatitis, death)
|
|
|
What type of diet leads to Niacin (B3) deficiency?
|
Diets made up primarily of maize (corn product)
|
|
|
What amino acid can be utilized to produce Niacin (B3)?
|
Tryptophan
|
|
|
What enzyme deficiency produces SCID?
|
Adenosine Deaminase (via feedback inhibition of ribonucleotide reductase, thereby preventing DNA synthesis & decreased lymphocyte counts)
|
|
|
What is the MC lysosomal storage disease?
|
Gaucher's Disease
|
|
|
What is the mechanism of Gaucher's disease?
|
Beta-glucocerebrosidase deficiency -> accumulation of glucocerebrosidase
|
|
|
What is the molecule accumulated in Gaucher's disease?
|
Glucoberebrosidase
|
|
|
What are the Sx of Gaucher's disease?
|
HSM, aseptic necrosis of femur, bone crises, macrophages that look like crumpled tissue paper
|
|
|
What is the genetic mechanism of Gaucher's disease?
|
Autosomal Recessive
|
|
|
What enzyme is deficienct in Fabry's disease?
|
Alpha-galactosidase A
|
|
|
What is the molecule accumulated in Fabry's disease?
|
Ceramide Trihexoside
|
|
|
What is the genetic mechanism of Fabry's disease?
|
X-linked Recessive
|
|
|
What lysosomal storage disease results in peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular & renal disease?
|
Fabry's Disease
|
|
|
What enzyme is deficienct in Krabbe's disease?
|
Galactocerebrosidase
|
|
|
What is the molecule accumulated in Krabbe's disease?
|
Galactocerebroside
|
|
|
What is the genetic mechanism of Fabry's disease?
|
Autosomal Recessive
|
|
|
What lysosomal storage disease results in peripheral neuropathy, developmental delay, optic atrophy, and globoid cells?
|
Krabbe's Disease
|
|
|
What lysosomal storage disease results in developmental delay, gargoylism, airway obstruction, HSM, and corneal clouding?
|
Hurler's Syndrome (Hurlers don't need to see)
|
|
|
What lysosomal storage disease results in mild developmental delay, mild gargoylism, mild HSM, and aggressive behavior?
|
Hunter's Syndrome (Hunters are aggressive & need to see)
|
|
|
What is the genetic mechanism of Hurler's Syndrome?
|
Autosomal Recessive
|
|
|
What is the genetic mechanism of Hunter's Syndrome?
|
X-linked Recessive
|
|
|
What is the rate controlling enzyme of the cholesterol metabolic pathway?
|
HMG-CoA Reductase
|
|
|
What is the target of the statin drugs?
|
HMG-CoA Reductase
|
|
|
What reaction is catalyzed by HMG-CoA Reductase?
|
HMG-CoA -> mevalonate/mevalonic acid
|
|
|
How do statins work?
|
They lower serum cholesterol by reducing de novo synthesis of cholesterol.
|
|
|
When is HMG-CoA active?
|
When blood glucose is high (insulin increases, glucagon decreases levels)
|
|
|
What is the rate controlling enzyme of the pentose phosphate pathway?
|
Glucose 6-P DH
|
|
|
What reaction is catalyzed by Glucose 6-P DH?
|
Glucose 6-P DH + NADP -> 6-Phosphogluconae + NADPH
|
|
|
What is the MCC of hemolytic anemia?
|
G6PD deficiency (RBCs contain Heinz bodies)
|
|
|
What is the genetic mechanism of G6PD deficiency?
|
X-linked Recessive
|
|
|
What can trigger a G6PD crisis and/or Steven Johnson syndrome?
|
Anything that induces oxidative stress (i.e. anti-malarial or sulfa drugs, fava beans, infection)
|
|
|
What is the purpose of the pentose phosphate pathway?
|
To produce NADPH and ribulose-5-phosphate, which is used for nucleotide synthesis.
|
|
|
What is NADPH used for?
|
Biosynthesis, maintenance of reduced glutathione (protection vs ROS) and bactericidal activity by PMNs.
|
|
|
What activates G6PD?
|
Insulin & NADP
|
|
|
What enzyme allows for conversion of extraneous 3-C product of beta oxid of odd-chain FAs to products which can be used in the TCA cycle?
|
Methylmalonate CoA Mutase
|
|
|
What reaction is catalyzed by Methylmalonate CoA Mutase?
|
Methylmalonyl CoA --> Succinyl CoA
|
|
|
What cofactor is required by methylmalonate CoA mutase?
|
B12!!!
|
|
|
If not corrected, what can B12 deficiency lead to?
|
Megaloblastic anemia & peripheral neuropathy (b/c abberant FA's are incorporated into myelin sheaths)
|
|
|
Excretion of what acid indicates B12 deficiency over folate deficiency?
|
Methylmalonic Acid
|
|
|
What is the role of UDP-Glucuronyltransferase?
|
Glucuronidation rxn (phase II – conjugation of non-soluble substances/drugs/bilirubin to prepare for excretion)
|
|
|
What reaction is catalyzed by UDP-Glucuronyltransferase?
|
Transfer of glucuronosyl group from uridine 5’-diphospho-glucuronic acid (UDPGA) to substrate molecules.
|
|
|
What enzyme deficiency leads to physiology jaundice?
|
At birth there are low levels of UDP-Glucuronyltransferase, which leads to phsyiologic jaundice (and kernicterus) if left unchecked.
|
|
|
What is the genetic mechanism of Crigler-Najjar syndrome?
|
Autosomal Recessive
|
|
|
What enzyme is deficienct in Crigler-Najjar syndrome?
|
UDP-Glucuronyltransferase
|
|
|
What is the result of an absence of UDP-Glucuronyltransferase?
|
Crigler-Najjar syndrome -> Extreme jaundice in newborns
|
|
|
How do you treat Crigler-Najjar syndrome?
|
Phototherapy, exchange transfusions, heme oxygenase inhibitors, and liver transplant
|
|
|
What is Gilbert syndrome?
|
Reduced UDP-Glucuronyltransferase activity leading to mild elevation of unconjugated bilirubin during times of stress
|
|
|
What is the genetic mechanism of Gilbert syndrome?
|
Autosomal Recessive
|
|
|
What enzyme allows for conversion of homocysteine to S-adenosylmethionine (SAM)?
|
Homocysteine Methyltransferase
|
|
|
Why is 5-adenosylmethionine (SAM) important?
|
It is an important molecule that donates methyl groups (required for purine, thymidine, epinephrine and mRNA sythesis)
|
|
|
What reaction is catalyzed by Homocysteine Methyltransferase?
|
Homocysteine -> Methionine
|
|
|
What cofactors are required by Homocysteine Methyltransferase?
|
B12 & Folic Acid
|
|
|
What does homocysteine methyltransferase deficiency cause?
|
Homocysteinuria (rare) -> ↑ oxidation of LDL particles -> dislocated lenses, DVT, stroke, atherosclerosis (in kids), mental retardation, MI <20yo
|
|
|
What is the MCC of homocysteinuria?
|
Vitamin Deficiency (B12, B6, Folic Acid)
|
|
|
What is the most important enzyme in de novo pyrimidine synthesis?
|
Dihydrofolate Reductase
|
|
|
What reaction is catalyzed by dihydrofolate reductase?
|
Dihydrofolate -> Tetrafolate
|
|
|
What drugs target dihydrofolate reductase?
|
Methotrexate (antineoplastic, eukaryotic S phase), Trimethoprim (antibiotic, prokaryotic), & Pryimethamine (antiprotozoal)
|
|
|
What enzyme salvages purines from degraded DNA to renewed purine synthesis?
|
HGPRT
|
|
|
What reacion is catalyzed by HGPRT?
|
Guanine + PRPP -> GMP
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|
|
What drug is converted to its active form by HGPRT?
|
Allopurinol
|
|
|
What enzyme deficiency leads to Lesch-Nyhan syndrome?
|
HGPRT
|
|
|
What is the genetic mechanism of Lesch-Nyhan syndrome?
|
X-linked Recessive
|
|
|
What are the consequences of HGPRT deficiency?
|
Lesch-Nyhan syndrome -> hyperuricemia & hyperuricosuria -> mental retardation, spastic cerebral palsy w/ compulsive biting of hands & lips, death
|
|
|
What is a secondary consequence of HGPRT deficiency?
|
Poorly utilized B12 -> megaloblastic anemia
|
|
|
True/False - Both behavior and gout Sx of Lesch-Nyhan syndrome respond well to allopurinol.
|
False - Only the gout Sx of Lesch-Nyhan syndrome respond to allopurinol.
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|
|
What enzyme allows for the degradation of the branched chain amino acids?
|
Branched Chain Ketoacid DH
|
|
|
What are the branched chain amino acids?
|
Val, Ile, Leu
|
|
|
What reaction is catalyzed by Branched Chain Ketoacid DH?
|
Val, Ile, Leu -> acetyl CoA or Propionyl CoA
|
|
|
What cofactors are required by Branched Chain Ketoacid DH?
|
Thiamine diphosphate, FAD, NAD, Lipoate, CoA
|
|
|
What enzyme deficiency leads to Maple Syrup Urine Disease?
|
Branched Chain Ketoacid DH (I Love Vermont)
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|
|
What is the typical course of Maple Syrup Urine Disease?
|
Infants: 1-3 days = normal; 3+ days = progressive lethargy, wt loss, alternating hypertonia & hypotonia, characteristic maple syrup urine
|
|
|
What is the treatment for Maple Syrup Urine Disease?
|
Restriction of dietary Ile, Leu, Val
|
|
|
If not corrected, what can Maple Syrup Urine Disease lead to?
|
Ketosis, Coma, Death
|
|
|
What are the essential amino acids?
|
Ile, Leu, Lys, Met, Phe, Thr, Trp, Val, His* (PVT TIM HALL -> His is only essential in infants)
|
|
|
What are the nonessential amino acids?
|
Ala, Asp, Asn, Cys, Glu, Gln, Gly, Pro, Ser, Tyr, Arg)
|
|
|
What are the positively charged (acidic) amino acids?
|
Arg, His, Lys
|
|
|
What are the negatively charged (basic) amino acids?
|
Asp, Glu
|
|
|
What are the nonpolar amino acids?
|
Ala, Cys, Gly, Ile, Leu, Met, Phe, Pro, Trp, Val
|
|
|
What are the polar amino acids?
|
Arg, Asn, Asp, Glu, Gln, His, Lys, Ser, Thr, Tyr
|
|
|
What are the aromatic amino acids?
|
Phe, His, Tyr, Trp
|
|
|
What are the sulfur-containing amino acids?
|
Cys, Met
|
|
|
What enzyme aids Vit K in the formation of Ca2+ binding site on Ca2+-dependent proteins?
|
Vitamin K Decarboxylase (gamma-Glutanylcarboxylase)
|
|
|
What are the Ca-dependent proteins aided by Vitamin K Decarboylase?
|
II, VII, IX, X, protein C, protein S
|
|
|
What cofactor is required by gamma-Glutanylcarboxylase?
|
Vitamin K
|
|
|
What are the Sx of Vitamin K deficiency?
|
Prolonged bleeding, easy bruising, potentially fatal hemorrhagic disease
|
|
|
What conditions predispose to Vitamin K deficiency?
|
Fat malabsorption (Vit K is lipid-soluble), bile duct occlusion, prolonged Tx w/ broad spectrum antibiotics, breast-fed newborns (esp in home birth w/ no postnatal Vit K injection), mothers Tx w/ certain anticonvulsants (phenylhydantoins)
|
|
|
What drug indirectly inhibits the action of gamma-Glutanylcarboxylase (AKA Vitamin K Decarboxylase)?
|
Warfarin (through inhibition of Vitamin K recycling)
|
|
|
What enzyme catabolizes purines for excretion as urin acid?
|
Xanthine Oxidase
|
|
|
What reactions are catalyzed by Xanthine Oxidase?
|
Hypozanthine + H2O -> xanthine + H2O2 & Xanthine + H2O -> uric acid + H2O2
|
|
|
What drug inhibits the actions of Xanthine Oxidase?
|
Allopurinol
|
|
|
What is allopurinol used to treat?
|
Chronic Gout
|
|
|
What are the major characteristics of gout?
|
Hyperuricemia & needle-shaped crystals with negative bifringence upon microscopic evaluation of aspirated synovial fluid
|
|
|
What enzyme is involved in the hydrolysis of hexose-containing molecules (i.e. lipids & gangliosides)?
|
Hexosaminidase A
|
|
|
What is the result of an absence of Hexosaminidase A?
|
An inability to hydrolyze certain sphingolipids, causing accumulation of lipids within lysosomes
|
|
|
Tay-Sachs Disease is associated with a deficiency of what enzyme?
|
Hexosaminidase A
|
|
|
What is the genetic mechanism of Tay-Sachs disease?
|
Autosomal Recessive
|
|
|
What molecule is accumulated within lysosomes of patients with Tay-Sachs disease?
|
GM2 Gangliosides
|
|
|
What are gangliosides?
|
A glycosphginolipid + one or more sialic acids, commonly found in nervous tissue of the brain
|
|
|
What are the Sx of Tay-Sachs disease?
|
Cherry red spots in macula (normal macular surrounded by abnormal fatty tissue), blindness, psychomotor retardation, death <2yrs
|
|
|
Tay-Sachs Disease is associated with what population?
|
Ashkenazi Jews
|
|
|
Why is Tay-Sachs disease considered one of the most important medical breakthroughs?
|
The inexpensive enzyme assay discovered to test for Tay-Sachs was one of the first mass-screening tools developed for the field of medical genetics
|
|
|
What is Sandhoff disease?
|
Clinically undistinguishable from Tay-Sachs, Sandhoff disease is a defiency in hexosaminidase A & B leading to an accumulation of GM2 gangliosides within lysosomes
|
|
|
What is the genetic mechanism of Sandhoff disease?
|
Autosomal Recessive
|
|
|
What enzyme catalyzes the conversion of galactose into glucose?
|
Galactose-1-P-Uridyltransferase (GALT)
|
|
|
Deficiency of GALT leads to what clinical situation?
|
Galactosemia
|
|
|
What is Galactosemia?
|
Ingestion of milk by infants results in vomiting, lethargy, jaundice, hepatopathy, renal failure
|
|
|
What is the treatment for Galactosemia?
|
Lactose-free, galactose-reduced diet
|
|
|
If left untreated, what are the consequences of galactosemia?
|
Severe damage of kidneys, liver, lenses, mental retardation
|
|
|
What enzyme links the glycolysis metabolic pathway to the TCA cycle or FA biosynthesis?
|
Pyruvate DH
|
|
|
True/False - Pyruvate DH is an irreversible reaction.
|
TRUE
|
|
|
What cofactors are required by pyruvate DH?
|
Thiamine pyrophosphate (from thiamine), Lipoic acid, CoA, FADH2 (from riboflavin), NADH (from niacin) “Tender Loving Care For Nancy”
|
|
|
Deficiency of pyruvate DH leads to what clinical situation?
|
Lactic Acidosis
|
|
|
What types of patients are especially prone to deficiency of pyruvate DH?
|
Alcoholics - Due to chronic thiamine deficiency
|
|
|
How should you treat an alcoholic patient presenting to the ER with lactic acidosis?
|
Give thiamine first, then glucose replacement (prevents complete conversion to lactic acid & worsening of the overall condition)
|
|
|
What enzyme provides malonyl CoA substrate for the biosynthesis of FAs?
|
Acetyl CoA Carboxylase
|
|
|
What cofactors are required by Acetyl CoA Carboxylase?
|
Biotin, ATP, CO2
|
|
|
What is the rate-limiting step of FA biosynthesis?
|
Acetyl CoA Carboxylase
|
|
|
What activates Acetyl CoA Carboxylase?
|
Insulin & Citrate
|
|
|
What enzyme hydrolyzes triglycerides to FAs and glycerol?
|
Hormone Sensitive Lipase
|
|
|
When is Hormone Sensitive Lipase active?
|
Fasting States - decreased insulin, increased glucagon, increased Epi, increased Cortisol
|
|
|
Deficiency of Carbamoyl Phosphate Synthetase I leades to what clinical Sxs?
|
↑ [NH4], hyperammonemia, ↑glutamine, ↑BUN, NO increase in uracil or orotic acid, lethargy, convulsions, coma, death
|
|
|
Deficiency of Ornithine Transcarbamoylase leades to what clinical Sxs?
|
↑ [NH4], hyperammonemia, ↑glutamine, ↑BUN, YES increase in uracil or orotic acid, lethargy, convulsions, coma, death
|
|
|
How do you treat deficiencies of either Carbamoyl Phosphate Synthetase I or Ornithine Transcabamoylase?
|
Low protein diet, administration of sodium benzoate or phenylpyruvate to capture excess nitrogen
|
|
|
What is marasmus?
|
Deficiency of all types of vitamins & nutrients (AKA starving to death)
|
|
|
What is kwashiorkor?
|
Deficiency of protein, leading to ascites & fatty liver
|
|
|
What is the MCC of B6/PLP deficiency?
|
Isonazid (INH) Therapy
|
|
|
What is scurvy?
|
Poor wound healing, easy bruising, bleeding gums, anemia
|
|
|
What is the MCC of scurvy?
|
Vitamin C Deficiency (lack of citrus fruits & green veggies)
|
|
|
What are the antioxidant vitamins?
|
Vitamins A, C, E
|
|
|
Where is Vitamin A especially utilized?
|
The retina (important for rods & cones) & epithelium
|
|
|
What are the Sx of Niacin (B3) deficiency?
|
Pellagra (diarrhea, dementia, dermatitis, death)
|
|
|
What type of diet leads to Niacin (B3) deficiency?
|
Diets made up primarily of maize (corn product)
|
|
|
What amino acid can be utilized to produce Niacin (B3)?
|
Tryptophan
|
|
|
What enzyme deficiency produces SCID?
|
Adenosine Deaminase (via feedback inhibition of ribonucleotide reductase, thereby preventing DNA synthesis & decreased lymphocyte counts)
|
|
|
What is the MC lysosomal storage disease?
|
Gaucher's Disease
|
|
|
What is the mechanism of Gaucher's disease?
|
Beta-glucocerebrosidase deficiency -> accumulation of glucocerebrosidase
|
|
|
What is the molecule accumulated in Gaucher's disease?
|
Glucoberebrosidase
|
|
|
What are the Sx of Gaucher's disease?
|
HSM, aseptic necrosis of femur, bone crises, macrophages that look like crumpled tissue paper
|
|
|
What is the genetic mechanism of Gaucher's disease?
|
Autosomal Recessive
|
|
|
What enzyme is deficienct in Fabry's disease?
|
Alpha-galactosidase A
|
|
|
What is the molecule accumulated in Fabry's disease?
|
Ceramide Trihexoside
|
|
|
What is the genetic mechanism of Fabry's disease?
|
X-linked Recessive
|
|
|
What lysosomal storage disease results in peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular & renal disease?
|
Fabry's Disease
|
|
|
What enzyme is deficienct in Krabbe's disease?
|
Galactocerebrosidase
|
|
|
What is the molecule accumulated in Krabbe's disease?
|
Galactocerebroside
|
|
|
What is the genetic mechanism of Fabry's disease?
|
Autosomal Recessive
|
|
|
What lysosomal storage disease results in peripheral neuropathy, developmental delay, optic atrophy, and globoid cells?
|
Krabbe's Disease
|
|
|
What lysosomal storage disease results in developmental delay, gargoylism, airway obstruction, HSM, and corneal clouding?
|
Hurler's Syndrome (Hurlers don't need to see)
|
|
|
What lysosomal storage disease results in mild developmental delay, mild gargoylism, mild HSM, and aggressive behavior?
|
Hunter's Syndrome (Hunters are aggressive & need to see)
|
|
|
What is the genetic mechanism of Hurler's Syndrome?
|
Autosomal Recessive
|
|
|
What is the genetic mechanism of Hunter's Syndrome?
|
X-linked Recessive
|
|
|
What enzyme is defective in von Gierke disease?
|
Glucose-6-Phosphatase (AKA Type I Glycogenosis)
|
|
|
What molecule is accumulated within hepatocytes & renal cells of patients with von Gierke disease?
|
Glycogen
|
|
|
What enzyme is defective in Pompe disease?
|
alpha-1,4-glucosidase (AKA Type II Glycogenosis)
|
|
|
What molecule is accumulated within hepatocytes & myocytes of patients with Pompe disease?
|
Glycogen
|
|
|
What enzyme is defective in Cori disease?
|
Amylo-1,6-glucosidase (AKA Type III Glycogenosis)
|
|
|
What molecule is accumulated within hepatocytes of patients with Cori disease?
|
Glycogen
|
|
|
What enzyme is defective in McArdle disease?
|
Muscle Phosphorylase
|
|
|
What molecule is accumulated within myocytes of patients with McArdle disease?
|
Glycogen
|
|
|
What enzyme is defective in Phenylketonuria?
|
Phenylalanine hydroxylase
|
|
|
What molecule is accumulated by patients with Phenylketonuria?
|
Phenylalanine & its degradation products
|
|
|
What enzyme is defective in Alkaptonuria?
|
Homogentisic Oxidase
|
|
|
What molecule is accumulated by patients with Alkaptonuria?
|
Homogentisic Acid
|
|
|
What is a cardinal sign of McArdle disease?
|
Muscle cramping & weakness following exercise
|
|
|
What is a cardinal sign of Alkaptonuria?
|
Urine turns dark upon standing & oncrhonosis (dark-stained tissues)
|
