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311 Cards in this Set

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What is the location, pathway, and nitrogen source of the carbamoyl phosphate synthetases?
CPS 1 - the "IA's"
Location = mitochondr-IA
Pathway = ur-EA
N-Source = ammon-IA

CPS II - the "Y's":
Location = cYtosol
Pathway = pYrimidine sYnthesis
N-Source = glYtamine
What is the rate limiting step of purine synthesis?
Glycine-PRPP Aminotransferase

(shortly after PRPP is formed)
What is the rate limiting step of pyrimidine synthesis?
CPS II = Carbamoyl phosphate synthetase II

Converts glutamine, CO2 & ATP into Carbomoyl phosphate
What are the sources of carbon in the formation of purines?
3 sources in Purines:
- THF
- CO2
- Glycine
What are the sources of carbon in the formation of pyrimidines?
2 sources in Pyrimidines:
- Carbomoyl phosphate / CO2
- Aspartate
What accounts for the positive charge of histones? The negative charge of DNA?
Histones d/t + Amino Acids:
- Lysine
- Arginine

DNA d/t Phosphate groups
How many adenine residues are found in a molecule of DNA if one strand has:
- A = 2000
- G = 500
- C = 1500
- T = 1000
= 3000

2000 A on one strand
1000 A on other (d/t 1000 T on original strand)
What strand of DNA nucleotides opposes:
5'-ATTGCGTA-3'?
5'-TACGCAAT-3'
(always written 5'→3'!!)
Which medication inhibits ribonucleotide reductase?
HU = Hydroxyurea
Which medication inhibits DHFR (Dihydrofolate reductase)?
MTX = Methotrexate (eukaryotes)
TMP = Trimethoprim (prokaryotes)

Prevent regeneration of THF
Which medication inhibits thymidylate synthase?
5-FU = 5-Flurouracil
Which medication inhibits inosine monophosphate dehydrogenase?
Mycophenylate
Which medication inhibits PRPP synthase?
6-MP = 6-Mercaptopurine
What are the characteristic features of orotic aciduria?
- ↑ orotic acid in urine
- NO hyperammonia
- megaloblastic anemia (doesn't correct w/ folate / B12)
- FTT (failure to thrive)
How does UV light damage DNA?
Forms Thymidine dimers on same strand of DNA (TT --> T^T)

Can be read as a single T --> frameshift mutation
What eukaryotic DNA polymerase replicates the lagging strand and synthesizes RNA primer?
DNA Polymerase α
What eukaryotic DNA polymerase repairs DNA?
DNA Polymerase ß and ε
What eukaryotic DNA polymerase replicates mitochondrial DNA?
DNA Polymerase Γ
What eukaryotic DNA polymerase replicates the leading strand DNA?
DNA Polymerase δ
Which antibiotic inhibits 50S peptidyltransferase?
Chloramphenicol
Streptogrammins
Which antibiotic binds 50S, blocking translocation?
Linezolid
Macrolides
Which antibiotic binds 30S, preventing attachment of tRNA?
Tetracyclines
Which antibiotic inhibitis prokaryotic RNA polymerase?
Rifampin
Which antibiotic inhibits prokaryotic topoisomerase?
Fluoroquinolones
Which antibiotic inhibits prokaryotic dihydrofolate reductase?
TMP = Trimethoprim
What are the 3 different mechanisms that cells employ to break down proteins?
1) Ubiquitinization
2) Lysosomal degradation
3) Ca-dependent enzymes
What enzyme catalyzes peptide bond formation during protein synthesis?
Peptidyltransferase
(ribozyme)
What enzyme matches amino acids to tRNA?
Aminoacyl-tRNA Synthetase
What are the mRNA STOP codons?
UGA
UAA
UAG

Remember: NO UGGs
What are the different RNA polymerases in eukaryotes?
RNA Polymerase I = rRNA
RNA Polymerase II = mRNA
RNA Polymerase III = tRNA
What amino acid frequently has more coding sequences in the mRNA than are represented in the peptide that is created from that mRNA?
Methionine

AUG = start = methionine
usually cleaved off
How is hnRNA processed before it leaves the nucleus?
1) Capped (5')
2) Tail (3' Poly-A)
3) Splicing out of introns
What is the characteristic sequence of the promoter region? What does a mutation in the sequence cause?
Upstream "Boxes":
- CAAT (-75)
- TATA (-25)

Mutation will result in decrease in the amount of gene product transcribed.
What enzyme is deficient in Lesch-Nyhan syndrome? What is the Tx?
HGPRT = Hypoxanthine-Guanine Phospho-Ribosyl-Transferase.

Tx = Allopurinol (only help w/ hyperuricemia)
What structural motifs allow for proteins to bind to DNA?
1) Helix-LOOP-helix
2) Helix-TURN-helix
3) Zinc finger
4) Leucine Zipper
What autosomal dominant disease is a/w a floppy mitral valve, dissecting aortic aneurysms & berry aneurysms?
Marfan's syndrome
What autosomal dominant disease is a/w mitral valve prolapse, liver disease, and berry aneurysms?
ADPKD = autosomal dominant polycystic kidney disease
What autosomal dominant disease is a/w neural tumors and pigmented iris hamartomas?
Neurofibromatosis Type 1
Chromosome 17

NF1 → neurofibromin
(important to regulate RAS in schwann cells & other neural crest derivatives)
What autosomal dominant disease is a/w colon cancer (VERY strong)
FAP = Familial adenomatous polyposis

APC gene = A-fter P-uberty → C-ancer
(Chromosome 5)

APC also a/w Gardner's syndrome
What autosomal dominant disease is a/w an MI before age 20?
Familial hypercholesteremia

Lack/Defect of LDL-R
- Aa → 300+
- AA → 700+

a/w tendon xanthomas (achilles tendon)

Other MI b/4 20 y/o = hypertrophic cardiomyopathy
What autosomal dominant disease is a/w hemangioblastomas of retina, cerebellum, and medulla?
vHL = von Hippel-Lindau

VHL is a tumor suppressor that moderates HIF → angiogenesis

Also a/w:
- renal cell carcinoma (bilateral, multiple)
- pheochromocytoma
What autosomal dominant disease is a/w increased MCHC and hemolytic anemia?
Hereditary spherocytosis

Defective:
- spectrin
- ankyrin
lead to round RBC's

Dx = osmotic fragility test
Tx = splenectomy
What autosomal dominant disease is a/w bilateral acoustic neuromas?
Neurofibromatosis Type 2
Chromosome 22

NF2 → merlin

Schwannomas
What autosomal dominant disease is a/w caudate atrophy and dementia?
Huntington disease
- CAG repeats; anticipation; 40 y/o

the C's (#3) and D's (#4) of HD:
- 3 nucleotides = CAG:
- C - ↓ CNS amounts of:
- A - ACh
- G - GABA
4 = associated symptoms:
- C - Chorea
- C - Caudate atrophy
- D - Dementia
- D - Depression
What autosomal dominant disease is a/w facial lesions, seizure disorder, and increased cancer risk?
Tuberous sclerosis

Systemic:
- Skin = adenoma sebaceum & "ash leaf spots"
- CNS = hamartomas (retina, cortex) → seizures, MR
- Cardiac = rhabdomyomas
- Renal = cysts & angiomyolipomas
What autosomal dominant disease is a/w cystic medial necrosis of the aorta?
Marfan's syndrome

Leads to:
- aortic incompetence
- dissecting aortic aneurysms
What autosomal dominant disease is a/w dwarfism that has short limbs but normal head & trunk?
Achondroplasia

FGF-R 3

a/w advanced PATERNAL age
Which lysosomal storage disease is a/w renal failure?
Fabry's disease

Tx = dialysis
What are the only 2 XLR lysosomal storage diseases? What is the method of inheritance of the others?
Fabry's disease
Hunter's syndrome

Rest are AR
What is the most common lysosomal storage disease?
Gaucher's disease
Which lysosomal storage diseases are a/w an early death (by age 3)?
1) Tay-Sachs
2) Niemann-Pick
3) Krabbe's
Which lysosomal storage disease is a demyelinating disease?
Metachromatic Leukodystrophy
How might:
- corneal clouding
- mental retardation
help distinguish between the mucopolysaccharidoses?
CC = Corneal clouding
MR = Mental retardation
Hurler's - CC + MR
Hunter's - MR only
Scheie's - CC only
I-cell - CC & may/may not MR
Which lysosomal storage disease is characterized by a deficiency in α-L-iduronidase?
Hurler's
(& Scheie's)
Which lysosomal storage disease is characterized by a deficiency in Iduronate sulfatase?
Hunter's
(XLR)

~ milder hurler's w/o corneal clouding
Which lysosomal storage disease is characterized by a deficiency in Arylsulfatase A?
Metachromatic leukodystrophy

- CNS/PNS demyelination
Which lysosomal storage disease is characterized by a deficiency in α-galactosidase?
Fabry's disease
(XLR)
Which lysosomal storage disease is characterized by a deficiency in ß-alactocerebrosidase?
Krabbe's

-Globoid cells
Which lysosomal storage disease is characterized by a deficiency in ß-glucocerebrosidase?
Gaucher's
(Most common)

Gaucher's cells = crumpled tissue paper
Which lysosomal storage disease is characterized by a deficiency in Hexosaminidase?
Tay-Sach's disease

(Sax = Hex)
- Onion skin lysosomes
- NO HSM (vs Niemann-Pick)
Which lysosomal storage disease is characterized by a deficiency in Sphingomyelinase?
Niemann-Pick

- Foam cells

Nie Man Pick's his nose with his SPHINGer
Which lysosomal storage disease is characterized by an accumulation of GM2 ganglioside?
Tay-Sach's
Which lysosomal storage disease is characterized by an accumulation of heparan/dermatin sulfate?
Hurler's, Hunter's & Scheie's
(basically all the mucopolysaccharidases)
What lysosomal storage diseases are common among Ashkenazi Jews?
1) Tay-Sach's (Cherry)
2) Niemann-Pick (Cherry, HSM)
3) Gaucher's (some forms)
Which lysosomal storage disease is characterized by cells w/ "crinkled paper cytoplasm"?
Gaucher's disease
(most common)

Gaucher's cells = Macrophages
What is the DDx for Cherry-Red Spot on the retina?
1) Lysosomal Storage Disease
- Tay-Sach's
- Niemann-Pick (w/ HSM)
2) Vascular
- Central retinal artery occlusion
What is the mode of inheritance for glycogen storage disease?
AR
What is the mode of inheritance for fragile X?
XLR

FMR1 gene
FMRP protein
What is the mode of inheritance for polycystic kindey diseases (adult and infant)?
adult = AD → PKD1
infant = AR
What is the mode of inheritance for PKU?
AR

defective PAH = Phenylalanine hydroxylase
What is the mode of inheritance for hereditary spherocytosis?
AD

Defective:
- spectrin
- ankyrin
What is the mode of inheritance for duchenne's MD?
XLR

deletion of dystrophin
(frameshift mutation)
What is the mode of inheritance for familial adenomatous polyposis?
AD

APC gene (chromosome 5)
What is the mode of inheritance for Lesch-Nyhan?
XLR

HGPRT deficiency → hyperuricemia
What is the mode of inheritance for Bruton's agammaglobulinemia?
XLR

BTK gene → tyrosine kinase that allows pro-B cells → pre-B cells
What is the mode of inheritance for thalessemias?
AR
What is the mode of inheritance for sickle cell anemia?
AR
What is the mode of inheritance for Wiscott-Aldrich syndrome?
XLR (part of the "WBC's")

→ progressive deletion of B and T Cells
What is the mode of inheritance for von ecklinghausen's Dz?
aka Neurofibromatosis 1

AD

NF1 (17) → mutation of neurofibomin protein which regulates RAS
What is the mode of inheritance for von Hippel-Lindau Dz?
AD

VHL gene (3) → disabled tumor suppressor so constitutive expression of HIF → angiogenesis
What is the mode of inheritance for Hemophilia?
XLR

A = FVIII
B = FIX
What is the mode of inheritance for Mucopolysaccharidosis?
Hurler's = AR
(& Schiei's)
Hunter's = XLR
What is the mode of inheritance for familial hypercholesterolemia?
AD

LDL-R defective/absent

More severe in homozygotes
What is the mode of inheritance for sphingolipidosis?
Fabry's = XLR

AR:
- Gaucher's (most common)
- Niemann-Pick
- Tay-Sach's
- Krabbe's
- Metachromatic leukodystrophy
What is the mode of inheritance for Marfan's syndrome?
AD

Fibrillin gene mutation
What is the mode of inheritance for CF?
AR

CFTR gene (7; deletion of Phe 508)
What is the mode of inheritance for hemochromatosis?
AR

(1º form) → HFE gene?
abnormally high intestinal absorption of Fe
What is the mode of inheritance for G6PD Deficiency?
XLR
What is the probability that a female heterozygote for an XL disease will pass it on to her son?
50%
What is the probability that a female heterozygous for an XL disease that mates w/ a normal male will have a carrier daughter?
25%
What is the probablity that a female carrier of an XL disease will have a child w/ that disease assuming she mates a normal male?
25%
What genetic disease is associated with a floppy mitral valve, dissecting aortic aneurysms, and berry aneurysms?
Marfan's syndrome.
AD
Fibrillin gene mutation
What genetic disease is associated with mitral valve prolapse, liver disease, and berry aneurysms?
ADPKD
AD
PKD1 (16)
What genetic disease is associated with hemangioblastomas of the retina, cerebellum and medulla?
von Hippel-Lindau

VHL gene --> fails to suppress HIF --> angiogenesis
What genetic disease is associated with increased MCHC and hemolytic anemia?
Hereditary spherocytosis.
AD
Dysfx of:
- spectrin
- ankyrin
What genetic disease is associated with cafe-au lait spots and soft tissue growths?
Neurofibromatosis 1 (aka von Recklinghaus)
AD
NF1
What genetic disease is associated with macroochidism and autism?
Fragile X syndrome
XLR
FMR1 gene --> FMRP
What genetic disease is associated with endocardial cushion effects (being very common)?
Down Syndrome
Trisomy
What genetic disease is associated with recurrent pulmonary infections and steatorrhea?
Cystic fibrosis
AR
CFTR gene (7; Phe 508)
What genetic disease is associated with multiple fractures and is easily confused w/ child abuse?
Osteogenesis Imperfecta
AD
Type-1 Collagen problem
What genetic disease is associated with Alzheimer's disease after age 35?
Down syndrome
Trisomy 21
What genetic disease is associated with bilateral acoustic schwannomas?
Neurofibromatosis 2
AD
Merlin mutation
What genetic disease is associated with excessive fibro-fatty tissue deposits amongst muscle?
Duchenne's muscular dystrophy.
XLR
DMD gene → Dystrophin gene

Pseudohypertrophy common in calf muscles
What test is used to diagnose cystic fibrosis? Which gene is defective?
Dx: Chloride sweat test (excess Cl-) >60meq/L

CFTR gene is defective (codes for Cl- channel)
What is the difference b/w Southern, Northern, and Western blots?
South = DNA sample, DNA probe
North = RNA sample, DNA probe
West = Protein sample, Ab probe
Which lysosomal storage disease is a/w accumulation of GM2 ganglioside?
Tay-Sach's disease
Which lysosomal storage disease is a/w renal failure?
Fabry's disease
Which lysosomal storage disease is a/w accumulation of dermatin sulfate?
Both of the mucopolysaccharidoses:
- Hurler's
- Hunter's
- Scheie's
Which lysosomal storage disease is a/w deficiency in hexosaminidase?
Tay-Sach's disease

(Sax - Hex)
Two pt's have the same mutation on chromosome 15 but different phenotypic expresions; one received the mutation from the father while the other from the mother. What is this an example of?
Imprinting

This is chromosome 15:
- PW = deletion on paternal
- Angelman = deletion on maternal

also can be d/t uniparental disomy
What glycogen storage disease is a/w glycogen phosphorylase deficiency?
Type V = McArdle's disease

glycogen phosphorylase in skeletal muscle (breaks α1,4 bonds)
What glycogen storage disease is a/w glucose-6-phosphatase deficiency?
Type I = Von Gierke's

also can't complete gluconeogenesis
What glycogen storage disease is a/w lactic acidosis, hyperlipidemia, and hyperuricemia?
Type I = Von Gierke's

d/t severe hypoglycemia
What glycogen storage disease is a/w α-1,6-glucosidase deficiency?
Type III = Cori's

aka Debranching enzyme
What glycogen storage disease is a/w α-1,4-glucosidase deficiency?
Type II = Pompe's

(is the lysosomal enzyme that can break the 1,4 bonds)
What glycogen storage disease is a/w cardiomegaly?
Type II = Pompe's

Pompe's messes w/ the Pump
What glycogen storage disease is a/w diaphragm weakness that leads to respiratory failure?
Type II = Pompe's (the adult type)
What glycogen storage disease is a/w increased glycogen in liver and severe fasting hypoglycemia?
Type I = Von Gierke's
What glycogen storage disease is a/w hepatomegaly, hypoglycemia, hyperlipidemia, but with normally functioning kidneys, lactate and uric acid?
Type III = Cori's

Milder than Von Gierke's but still problematic (NOTE: normal lactate)
What glycogen storage disease is a/w painful muscle cramps & myoglobinuria with strenuous exercise?
Type V = McArdle's
What glycogen storage disease is a/w severe hepatosplenomegaly and enlarged kidneys?
Type I = Von Gierke's
Why are alanine and glutamine found in such high concentrations in the blood?
They are the 2 major carriers of nitrogen from tissues to the liver (to be used in the urea cycle).

Alanine is just a pyruvate that gets an NH3 from glutamate.

Glutamine is a glutamate with an additional NH3.
What is generally involved in transamination?
The trans-fer of an amino-group (NH3) to α-ketoglutarate → glutamate.
What enzyme catalyzes transamination?
Aminotransferases.

Named by the donor of the amino group:
- alanine aminotransferase takes NH3 from alanine leaving behind pyruvate.
What is required by all aminotransferases?
Pyridoxal phosphate, a derivative of Vitamin B6
What are the 2 most important aminotransferase enzymes and what reactions do they catalyze?
1) ALT = Alanine aminotransferase
- alanine + αKG → pyruvate + glutamate
2) AST = Aspartate aminotransferase
- alanine + α-KG → oxaloacetate + glutamate
What fuels are used/produced in the post-absorptive period?
Produced:
- Glucose (liver)
- FA's (adipose)

Used:
- glucose (muscle, brain, etc)
When does gluconeogenesis begin in the post-absorptive period? When does it become fully active?
Begins = 4-6 hours post-prandially

Fully active = 10-18 hours post-prandially (glycogen stores depleted)
How does the pattern of fuel production and usage change in early starvation? (24 hours)
Produced:
- glucose (gluconeogenesis & glycogenolysis)
- FA's (adipose)

Used:
- brain = glucose
- muscles = FA > glucose
In intermediate starvation (48 hours) how does the pattern of fuel production / consumption change?
Produced:
- glucose (gluconeogenesis only)
- ketosis (liver)
- FA's (adipose)

Used:
- Brain = glucose > ketones
- Muscles = FA's > ketones
What metabolic scenario favors the synthesis of ketone bodies?
Excess of Acetyl-CoA from FA Metabolism
What is the pattern of fuel utilization and production in prolonged starvation (5+ days)?
Produced:
- glucose (gluconeogenesis)
- ketones (liver)
- FA's (adipose)

Used:
- Brain = ketones
- muscles = FA's > ketones
Comparing an overnight fast and 3 day fast, what % energy comes from glucose? ketone bodies?
Overnight:
- 95% glucose / 5% ketones

3 Day Fast:
- 40% glucose / 60% ketones
What are the major regulatory enzymes of the citric acid cycle?
make citrate + the DH's:
1) citrate synthase
2) isocitrate dehydrogenase
3) αketoglutarate dehydrogenase
What is the rate-limiting enzyme for glycolysis?
PFK-1 = phosphofructokinase 1
What is the rate-limiting enzyme for gluconeogenesis?
FPB1 = fructose-1,6-bisphosphatase
What is the rate-limiting enzyme for TCA?
Isocitrate dehydrogenase
What is the rate-limiting enzyme for glycogenesis?
Glycogen synthase
What is the rate-limiting enzyme for glycogenolysis?
Glycogen phosphorylase (breaks α1,4)
What is the functional role of SAM?
S-adenosyl-methionine

1) methyl donor
2) generate phosphocreatine (as a backup for ATP)
What is the activated carrier for CO2?
Biotin
What is the activated carrier for glucose?
UPD-glucose
What is the activated carrier for electrons?
FADH2, NADH, NADPH
What is the activated carrier for one-carbon units?
THF (folate)
What is the activated carrier for acyl?
CoA & Lipoamide
How many ATP generated during aerobic metablism? Anaerobic?
Heart/Liver = 32
Muscles = 30

Anaerobic = 2 ATP + Lactate
What are the possible products of pyruvate?
1) Alanine
2) Oxaloacetate
3) Acetyl Co-A
4) Lactate
What irreversible enzymes are involved in gluconeogenesis?
4:
1) Pyruvate carboxylase (Pyr→OAA)
2) PEP carboxykinase (OAA→PEP)
3) F16BP*
(RLE)
4) G6Phosphatase (G6P→Glucose)
What is the primary energy source in a pt that has not eaten in two days?
FA's
Waht is the equation for Gibb's free energy?
dG = dH - (TxdS)
A stressed physician comes home, has 8 shots of tequila before dinner and becomes hypoglycemic; what happened?
EtOH induced hypoglycemia.

ADH's consume NAD+ → NADH.

This pushes:
- Pyruvate → Lactate
- OAA → Malate
therefore NO gluconeogenesis!!
A woman commonly develops intense muscle cramps and darkening in urine after exercise; what is her Dx?
McArdle's Disease (Type V glycogen storage disease)
- ↓ Glycogen phosphorylase in skeletal muscle
What is the name of the genetic syndrome a/w a 1000-fold increased risk of skin Ca?
Xeroderma pigmentosa
(DNA repair defect)
What is the name of the genetic syndrome a/w alcoholics leading to B1 deficiency & neurological defects?
Pyruvate dehydrogenase deficiency
What is the name of the genetic syndrome a/w abnormal collagen type I synthesis?
Osteogenesis imperfecta
What is the name of the genetic syndrome a/w absence of HGPRTase?
Lesch-Nyann Syndrome
What is the name of the genetic syndrome a/w deficiency of aldolase B?
Fructose intolerance

(FAB GUT)
What is the name of the genetic syndrome a/w defective excision repair & thymidine dimer formation?
Xeroderma pigmentosa
What is the name of the genetic syndrome a/w deficiency of cystathionine synthase?
Homocystinuria
What is the name of the genetic syndrome a/w Heinz bodies?
G6PD Deficiency
What is the name of the genetic syndrome a/w musty BO, albinism, MR, and eczema?
PKU = phenylketonuria
What is the name of the genetic syndrome a/w galactose-1-P uridyl transferase deficiency & causing MR, HSM and cataracts?
Galactosemia

(FAB GUT)
What is the name of the genetic syndrome a/w a Tx of NO Nutrasweet and ↑ dietary tyrosine?
PKU = Phenylketonuria
What is the name of the genetic syndrome a/w deficiency of tyrosinase?
Albinism
What is the name of the genetic syndrome a/w hyperextensible skin, loose joints, and bleeding tendency?
Ehlers-Danlos
What is the name of the genetic syndrome a/w decreased NADPH d/t lack of HMP enzyme?
G6PDH Deficiency
What is the name of the genetic syndrome a/w inherited defect in tubular amino acid transporter?
Cystinuria
(PCT for COLA AA's)
What is the name of the genetic syndrome a/w a Tx including ↓ Methionine and ↑ Cysteine & B6?
Homocystinuria
(Cystathione synthase deficiency)
What is the name of the genetic syndrome a/w deficiency in homogentisic acid oxidase?
Alkaptonuria (ochronosis)
(HGA oxidase)
What is the name of the genetic syndrome a/w hypoglycemia, jaundice, & cirrhosis?
Fructose intolerance
What is the name of the genetic syndrome a/w self-mutilation, gout, aggression, and choreathetosis?
Lesch-Nyann syndrome
What is the name of the genetic syndrome a/w blocked degradation of branched chain amino acids?
Maple syrup urine disease.

α-ketoacid dehydrogenase (Ile, Leu, Val)
What is the name of the genetic syndrome a/w bloating, cramps, and osmotic diarrhea?
Lactose intolerance
What is the name of the genetic syndrome a/w a Tx of acetazolamide to alkalinize the urine?
Cystinuria
What is the name of the genetic syndrome a/w a deficiency of BOTH B and T cells?
Adenosine deaminase deficiency
(SCID)
What is the name of the genetic syndrome a/w a Tx of ↓ fructose and sucrose intake?
Fructose intolerance
What is the name of the genetic syndrome a/w a Tx of increased ketogenic nutrient intake?
Pyruvate phosphatase deficiency
What is the name of the genetic syndrome a/w dark brown urine, organs, and connective tissue and is a benign disease?
Alkaptonuria.

(HGA oxidase deficiency)
What is the name of the genetic syndrome a/w multiple fractures and blue sclera?
Osteogenesis imperfecta
What is the name of the genetic syndrome a/w a Tx of exluding Galactose and Lactose from the diet?
Galactosemia
What are the essential amino acids?
PVT TIM HALL
Phe
Val
Thr
Trp
Ile
Met
His
Arg
Leu
Lys
What is the mechanism of action of lactulose?
Lactulose makes the gut lumen negative, trapping NH4+ (in cases of hyperammonemia)
What amino acid is a precursor of histamine?
Histidine

(B6 dependent)
What amino acid is a precursor of porphyrin (& heme)?
Glycine
What amino acid is a precursor of NO?
Arginine
What amino acid is a precursor of GABA?
Glutamate
What amino acid is a precursor of S-adenosyl-methionine (SAM)?
Methionine
What amino acid is a precursor of Creatine?
Arginine
Compare carbamoyl phosphate 1 to carbamoyl phophate 2?
CPS1 = mitochondria, urea cycle, NH3 from ammonia

CPS2 = cytoplasm, pyrimidine synthesis, NH3 from glutamine
What is the rate-limiting enzyme for the urea cycle?
CPS1 = carbamoyl phosphate synthase 1
What is the rate-limiting enzyme for the hexose monophosphate pathway?
G6PDH
What is the rate-limiting enzyme for fatty acid synthesis?
Acetyl-CoA Carboxylase
What is the rate-limiting enzyme for ketone body synthesis?
HMG-CoA Synthase
What is the rate-limiting enzyme for cholesterol synthesis?
HMG-CoA Reductase
What is the rate-limiting enzyme for bile acid synthesis?
7α-Hydroxylase
What is the rate-limiting enzyme for heme synthesis?
Aminolevulinate Synthase
What deficiency causes familial hypercholesterolemia?
↓LDL-R's

(hyperlipidemia type IIa)
A patient w/ PKU should have a diet low in phenylalanine. What other dietary modifications should this patient make?
1) Tyrosine supplementation
2) Replace THB cofactor (if deficient)
A full-term neonate becomes mentally retarded & hyperactive & has a musty odor. What is the diagnosis?
PKU

phenols = aromatic
What is the rate-limiting enzyme for ß-oxidation of FA's?
Carnitine acyltransferase
A 2 y/o girl has an increase in abdominal girth, failure to trhive, and skin & hair pigmentation. What is her diagnosis?
Kwashiorkor
A middle-aged man has dark spots on his sclera and has noted that his urine turns black when left sitting for a period of time. What is the Dx?
Alkaptonuria
A patient has a genetic disease in which the treatment includes protein restriction to prevent mental retardation, ketoacidosis, and death. What is the Dx?
Maple syrup urine disease
An 18 y/o female has moderate generalized abdominal pain, normal WBC and no fever. She has paresthesias in her lower extremities. What is her Dx?
Acute Intermittent Porphyria
A 45 y/o male alcoholic gets blistering lesions in sun-exposed areas especially the dorsum of the hands. He also has hypertrichosis of the face. What is the Dx?
Porphyria Cutanea Tarda
What is the treatment of homocystinuria?
1) ↓methionine
2) ↑cystine
3) ↑B6, B12, Folate
What protein is involved in transporting an endocytosed vesicle from the plasma membrane to the endosome?
Clathrin

(when numerous receptors are stimulated, their intracellular adaptin portions recruit clathrin. dynamin "pinches off" the phagosome.)
What molecule targets proteins in the ER for the lysosomes?
Mannose-6-phosphate

(absent in I-Cell disease)
What are the names of the B vitamins?
The Rich Never Pan Pyrite Filled Creeks

B1 = T - thiamine
B2 = R - riboflavin
B3 = N - niacin
B5 = P - pantothenic acid
B6 = P - pyridoxine
B9 = F - folic acid
B12 = C - cobalamin
What is the name of vitamin A?
Retinal, Retinol
What is the most common vitamin deficiency in the US?
Folic acid deficiency
What is the functionally active form of thiamine?
Vitamin B1 = Thiamine

TPP = Thiamine Pyrophosphate
In which reactions does the active form of Vitamin B1 have a role?
TPP is needed for:
1) Pyruvate dehydrogenase → Acetyl-CoA
2) αKG dehydrogenase (TCA)
3) Transketolase (HMP)
4) Branched-chain AA DH
How is thiamine deficiency diagnosed?
Increased RBC transketolase activity w/ addition of thiamine.
What 2 syndromes are associated w/ B1 deficiency? In what populations are they seen?
Ber1Ber1 & Wernicki-Korsakoff
1) BeriBeri = places w/ polished rice as major part of diet
2) W-K = Chronic Alcoholics
What characterizes Dry BeriBeri?
1) Nerves = Nonspecific PN w/ myelin degeneration
2) Drops = Toe, Wrist, Foot
3) Muscle = weakness
4) Reflexes = Low/absent
What characterizes Wet Beriberi?
1) Peripheral vasodilation
- cardiac failure (high-output)
- peripheral edema
2) Cardiomegaly
What are the clinical characteristics of Wernicke-Korsakoff syndrome?
Classic Triad (ACO - Kors-ACO-ff) = A-taxia, C-onfusino, O-phthalmoplegia

1) Gait Ataxia
2) Ophthalmoplegia = disturbances, nystagmus
3) Confusino - mental dysfx (apathy, listlessness, etc)
How is Niacin effective in treating Hyperlipidemia? What type specifically?
Niacine (B3) @ 100x the RDA:
used to tx Type IIb

Inhibits lypolysis in adipose leading to:
- less FFA's
- less FA's → liver
- less VLDL & therefore less LDL
What are some of the symptoms a/w riboflavin deficiency?
2C's of B2:
- C - Cheilosis (& angular stomatitis)
- C - Corneal vascularization

Also Glossitis
What are the biologically active forms of Riboflavin? What are they used for?
riboFlavin = B2

FMN
FAD
(generate 2 ATP = B2)

Used in RE-DOX rxn's
What are the biologically active forms of Niacin? What are they used for?
Niacin = B3

NAD+
NADP+
(generate 3 ATP = B3)

Used in RE-DOX rxn's
Which amino acid is required for generation of Niacin?
TryptophaN
What disease is caused by niacin deficiency? What are its symptoms?
Niacin = B3
Dz = Pellagra
Syx = 3D's of B3:
- Diarrhea
- Dermatitis
- Dementia
What population is prone to pellagra?
Populations that rely primarly on corn → B3 deficiency

Corn lacks tryptophan, so cannot synthesize.
What conditions may lead to pellagra?
Pellagra = Niacin (B3) deficiency d/t:
1) Hartnup Dz = ↓Trp absorption
2) Carcinoid Syn = ↑Trp metabolism
3) INH Rx = ↓B6 (to make Trp→B3)
What is the main SE of high dose Niacin treatment for hyperlipidemia? How is it prevented?
Flushing = peripheral dilation

Can reduce it by taking ASA
What is pantothenic acid and what is its role in metabolism?
Pantothenic acid = B5

Component of Co-A; Fx = transfer of acyl groups & FA synthesis
What is the biologically active form of pyridoxine?
Pyridoxine = B6

Active form = Pyridoxal Phophate
What is the metabolic function of pyridoxal phosphate?
Active form of B6

Coenzyme for numerous enzymes:
- AA metabolism (transaminations & deaminations)
- Glycogen phopsphorylates
- Decarboxylations
What drug can lead to deficiency of B6 and B3? What is it used to treat?
INH = Isoniazid

Tx for TB
What are the clinical findings of B6 deficiency?
Same as riboflavin:
- cheilosis
- stomatosis (angular)
- glossitis
+ nervous/neuro:
- convulsions
- hyperirritibility
- PN
In what metabolic reactions is folic acid involved? What is its biologically active form?
Synthesis of:
- T = Thymine
- A, G = Purines
(THF→TAG)

THF is active form
What deficiencies cause megaloblastic anemia?
B12 and B9 (Folate)
What is the result of excess folate?
B12 deficiency

Uses up B12 in converting excess Folate → THF
What is at the center of B12?
Cobalamin has a corrin ring @ the center which contains:

Cobalt
In what metabolic reactions is vitamin B12 involved?
2 rxn's for B12:

1) Homocysteine →methionine (using THF)
2) Methyl-malonyl CoA → Succinal-CoA
What are the steps of intake/absorption of B12?
1) Pepsin (gastric) releases B12
2) B12-Binding proteins (salivary; aka cobalophilins/R-binders)
3) Pancreatic proteases (R-B12 → B12 in duodenum)
4) IF binds (from parietal cells)
5) IF-B12 binds IF-R's (terminal ileum)
6) Transcobalamin II (serum) picks up
What is the Schilling test?
Radiolabeled B12; 4 stages:
1) B12 (IM normal; PO radio)
2) B12 + IF (Malabsorption)
3) B12 + Abx (SIBO)
4) B12 + Pancreatic enzymes
What is another name for B12 neuropathy?
Subacute combined degeneration

Also seen in:
- Vitamin E deficiency
- Friedreich's ataxia
What is usually the cause of B12 deficiency?
Autoimmune destruction of Parietal cells of the stomach (no IF)
What are 2 malabsorption problems that cause B12 deficiency?
Both in the terminal ileum:
1) Crohn's Dz
2) Celiac sprue
What is the metabolic role of biotin?
It's an Apoenzyme used in Carboxylation ("buy-a-tin of CO2")

PC
ACC
PPC
MCC
What can cause a deficiency in biotin?
1) Avidin glycoprotein (in egg whites)
2) Abx use (biotin synthesized by gut flora)
What is the main metabolic rxn of vitamin C? What are the others?
1) Collagen synthesis: Hydroxylation of:
- Proline
- Lysine
Also:
2) Catecholamines: DA → NE (dopamine ß-hydroxylase)
3) Fe Absorption: keeps in reduced Fe2+ state
What are the major signs of vitamin C deficiency?
Scurvy:
- Collagen:
- Sore, spongy gums
- Loose teeth
- Fragile BV's (hemorrhages, hemarthrosis)
- Impaired wound healing
- Fe absorption
- Anemia
What are the different forms of Vitamin A?
1) ß-carotene (from diet)
2) retinal (intestinal cleavage of ß-carotene → 2 retinal)
3) retinol
4) retinoic acid (byproduct of metabolism; helps w/ embryological patterning & the reason Vit A is teratogenic)
How is vitamin A stored in the body until it's needed? How is it transported?
Stored in Liver as Retinol esters.

Plasma Retinol-Binding Protein (RBP) transports
What are the broad metabolic functions of vitamin A?
1) Vision
2) Growth (embryologic)
3) Reproduction (spermatogenesis; prevent fetal absorption)
4) Epithelial cell maintenance (especially mucous secreting cells)
What disorders is vitamin A used to treat?
1) TOP Retinoic-Acid:
- acne
- psoriasis
2) PO Isotretinoin (Accutane)
- acne
3) Systemic:
- meAsles
- AmL (subtype M3)
What are the signs of Vitamin A deficiency?
B-lind K-ids N-eed X-ray vision:
B - Bitot's spots
K - Keratomalacia
N - Night blindness
X - Xerophthalmia
What are the signs of Vitamin A toxicity?
1) ↑ICP → H/A, N/V, stupor
2) Skin → dry, pruritic
3) Bone/Joint → pain
4) Liver → enlarged (cirrhotic?)
What populations are contraindicated for Vitamin A supplementation?
1) Pregnant women (teratogenic)
2) Smokers (↑ lung cancer risk)
What are the steps in Vitamin D metabolism?
1) Gut (D2) or Skin (D3)
2) BP (α1-globulin) binds → liver
3) 25-hydroxylase (liver)
4) 1αhydroxylase (kidney)
What is the precursor of Vitamin D in the skin?
7-dehydrocholesterol
What are the other names for types of vitamin D?
D2 = ERGOcalciferol
D3 = CHOLEcalciferol
1,25-(OH)2D3 = CalciTRIOL
What are the names for Vitamin D deficiency? What is the pathogenesis?
1) Rickets (kids)
2) Osteomalacia (adults)

↓VitD → ↓Ca → ↑PTH:
- Ca from bone
- Ca not excreted (renal)
- PO4 hyper-excreted (renal)

Hypophosphatemia → impairment of bone
What is the basic derangement found in rickets & osteomalacia?
Excessive UN-mineralized bone matrix
What are the common clinical manifestations of rickets?
R-ickets B-ends L-ittle P-eople:

R - Rachitic Rosary
B - Bow-legged
L - Lumbar Lordosis
P - Pectus carinatum

pp99
What disease is a/w vitamin D toxicity? Why?
Sarcoidosis

Epithelioid Macrophages also express 1α-hydroxylase
What is the principle role of Vitamin K?
Post-translational modification (gamma-carboxylation of glutamic acid) of clotting factors
What proteins rely on Vitamin K for their synthesis?
Clotting factors: 2, 7, 9, 10
Proteins C & S
What group is prone to Vitamin K deficiency and why?
Newborns.

Vitamin K synthesized by intestinal flora & not in breast milk.

Single 1mg IM dose @ birth.
What drugs cause Vitamin K deficiency w/ prolonged use?
1) Coumadin / Warfarin
2) Anticonvulsants
3) Abx's (lose gut bacteria)
What characterizes Vitamin K toxicity?
In an infant:
1) Hemolytic anemia
2) Jaundice
What is the other name for Vitamin E?
α-Tocopherol
What is associated w/ Vitamin E deficiency?
1) Subacute combined degeneration
- ataxia
- hyperreflexia
- impaired position/vibration (PN)
2) Proximal muscle weakness
3) Hemolytic anemia
What mutation results in Vitamin E deficiency?
AR - α-Tocopherol Transfer Gene Protein
A patient presents with convulsions and irritability. What vitamin deficiency is causing these symptoms?
Vitamin B6

Convulsions
Hyperirritability
PN
pp96
Which vitamin deficiency results in gum bleeding, bruising, anemia, and poor wound healing?
Vitamin C = Scurvy
Vitamin C is necessary for the hydroxylation of which amino acids of collagen synthesis?
Proline
Lysine
What vitamin, in excess, causes hypercalcemia?
Vitamin D
(also Vitamin A)
What vitamins have a function similar to reduced glutathione?
Vitamin A, C, E
An alcoholic develops a rash, diarrhea, and altered mental status. What is the vitamin deficiency?
B3 = Niacin

3 D's:
- Dementia
- Dermatitis
- Diarrhea
Which vitamin deficiency is a/w with increased RBC fragility?
Vitamin E
Which vitamin deficiency is a/w with dermatitis, cheilosis, glossitis?
Vitamin B2, B3, B9, B12 (and iron)
Which vitamin deficiency is a/w with PN, angular cheilosis, glossitis?
B12
Which vitamin deficiency is a/w with hemorrhagic disease?
Vitamin K
Which vitamin deficiency is a/w with neural tube defects?
B9 = Folate
Which vitamin deficiency is a/w with dermatitis, diarrhea, dementia?
B3 = Niacin
Which vitamin deficiency is a/w with megaloblastic anemia?
B9 (folate) and B12 (cobalamin)
Which vitamin deficiency is a/w with pernicious anemia?
B12
Which vitamin deficiency is a/w with Bitot's spots, keratomalacia, and xerophthalmia?
Vitamin A

B-lind K-ids N-eed X-ray vision
pp 95
Which vitamin deficiency is a/w with osteomalacia?
Vitamin D
Which vitamin deficiency is a/w with Rickets?
Vitamin D
Which vitamin can be used to Tx acne and psoriasis?
Vitamin A = TOP Retinoic Acid
Which vitamin is used in REDOX rxn's?
B2 (riboFlavin) and B3 (Niacin)
Which vitamin is used in carboxylation rxn's?
Biotin
Which vitamin is involved in the hydroxylation of prolyl residues?
Vitamin C

Proline
Lysine
Which vitamins are used by pyruvate dehydrogenase and α-ketoglutarate dehydrogenase?
T-ender L-oving C-are F-or N-oone

T - TPP [Thiamine] (B1)
L - Lipoic Acid
C - CoA (B5)
F - FAD (B2)
N - NAD (B3)
Which vitamin is given prophylactically to newborns?
Vitamin K
(1mg IM)
Which vitamin can be used to elevate HDL and lower LDL?
Niacin (B3)

Used to Tx Type IIb hyperlipidemia

SE = facial flushing
PPx = ASA
Which vitamin deficiency can be due to INH use?
B3 (Niacin) via B6 (pyridoxine)
What are the symptoms of zinc deficiency?
NO healing, sexing, shaving, smelling, tasting:

1) poor wound healing
2) hypogonadism
3) ↓ adult hair
4) anosmia
5) dysgeusia
What enzyme is inhibited by the drug fomepizole?
Alcohol Dehydrogenase

Tx for poisoning of:
- methanol
- ethylene glycol

it's Fo' - M & E - piz(oning)-ol (alcohol dehydrogenase) - e
What is the difference between kwashiorkor and marasmus?
Kwashiorkor = PROTEIN deficiency (mnemonic MEAL):
M - malnutrition
E - edema
A - anemia
L - liver (fatty)

Marasmus = ENERGY deficiency (M for Muscle wasting)
What vitamins should vegetarians supplement in their diet?
B12
What drugs act on microtubules?
P-rescribe M-icro-T-ubule G-rowth V-oiding C-hemicals:

P = Paclitaxel (-taxels)
M-T = Mebendazole, thiabendazole (-bendazoles)
G = Griseofulvin
V = Vincristine/vinblastine
C = Colchicine
What findings are a/w Ehlers-Danlos syndrome?
Ehlers-Danlos = type III collagen defect

a/w:
1) Hyperextensible skin
2) Bleeding/bruising (berry aneurysms)
3) Hypermobile joints
Which arachidonic acid product causes increased bronchial tone?
TXA2 = Thromboxane
LT = Leukotrienes
Which arachidonic acid product causes decreased bronchial tone?
PGE4, PGF4 = Prostaglandins
PGI4 = Prostacyclins
Which arachidonic acid product causes increased platelet aggregation?
TXA2 = Thromboxane
Which arachidonic acid product causes decreased platelet aggregation?
PGI4 = Prostacyclin
Which arachidonic acid product causes increased uterine tone?
PGE4, PGF4 = Prostaglandins
Which arachidonic acid product causes decreased uterine tone?
PGI4 = Prostacyclin
Which arachidonic acid product causes increased vascular tone?
TXA2 = Thromboxane
Which arachidonic acid product causes decreased vascular tone?
PGE4, PGF4 = Prostaglandins
PGI4 = Prostacyclin
What are the 2 most abundant substances in the plasma membrane?
Phospholipids
Cholesterol
What drugs act on the arachidonic acid pathway and where do they exert their function?
1) Steroids = PLA2
2) ZiLEUtin = LOX
3) NSAIDS/APAP/CeleCOXib = COX
4) ZafirLUkast/MonteLUkast = LT-Receptors
What provides the structural framework for DNA and the nuclear envelope?
Lamins A, B, and C
How are molecules transported to the nucleus?
Tagged w/ Nuclear Localization Signals rich in (+) AA's:
- Lysine
- Arginine