Vol. I - Biochem Flashcards
name the pyrimidines
Cytosine, uracil, thymine
Vitamin E deficiency
hemolytic anemia, acanthocytosis, weakness, posterior column demyelination (like B12)
B12 deficiency labs
high homocysteine AND high MMA levels
p53 –> Rb hypophosphorylation (activation) blocks
G1 to S transition
Deficiency in homologous recombination is found in:
BRCA1 mutation and Fanconi anemia
PKA is activated by
glucagon –> cAMP (in a fasting state)
Vitamin A (retinoic acid et al) deficiency
Night blindness, dryness, corneal degeneration, immunosupression
Lysosomal acid alpha 1,4 glucosidase (aka acid maltase) deficiency
Pompe disease
Homocystinuria presentation
HOMOCYstiene: high Homocysteine, Osteoporosis, Marfanoid habitus, Occular changes (down and in), Cardiovascular effects, kYphosis
Angelman syndrome mechanism
Paternal genes are silenced, disease occurs when maternal allele is lost
Rate limiting enzyme of de novo pyrimidine synthesis
Carbamoyl phosphate synthetase II
Function of 1,25 D3
increased intestinal absorption of Ca and PO4
increased bone mineralization (low levels)
increased bone resorption (high levels)
Most common lysosomal storage disease
Gaucher disease
Metachromatic leukodystrophy presentation
Central and peripheral demyelination –> ataxia and dementia
glycine is a precursor for
porphyrin –> heme
Rate limiting enzyme of fatty acid synthesis
Acetyl-CoA carboxylase
vitamin K dependent clotting factors
II, VII, IX, X, protein C and S
Is euchromatin expressed?
Yes - E is for expressed
citrate shuttle is required for
Fatty acid synthesis
VLDL apolipoproteins
Apo-E, C II, and B 100
Cause of Lesch-Nyhan syndrome
lack of HGPRT
Rate limiting enzyme of cholesterol synthesis
HMG-CoA reductase
Pyruvate dehydrogenase complex deficiency
x linked
pyruvate is shunted to lactate, high serum alanine
treat with ketogenic diet
Pathophysiology of Glucose-6-phosphate dehydrogenase deficiency
Reduced NADPH production –> not enough NADPH to reduce glutathione in RBCs –> vulnerable to oxidative damage (fava beans, sulfa drugs, nitrogen drugs) –> hemolytic anemia
Vitamin D deficiency
rickets in children, osteomalacia in adults
Purely glucogenic amino acids
Methionine, histidine, valine
Classic galactosemia is caused by
deficiency of galactose-1-phosphate uridyltransferase
Presentation of Lesch Nyhan syndrome
HGPRT: Hyperuricemia, Gout, Pissed off, Red/orange crystals in urine, Tense muscles
Fasting hypoglycemia, increased glycogen in liver, increased lactate, triglyceride, uric acid, hepatomegally
Von Gierke disease
Drugs that block pyrimidine synthesis:
Leflunomide and 5-FU/Capecitabine
Refsum disease defect
AR disorder of alpha-oxidation –> buildup of phytanic acid
Apo-C II function
lipoprotein lipase cofactor
hexokinase is found in
most tissues, not liver or beta cells
adrenoleukodistrophy defect
beta-oxidation (mutation in ABCD1)
Drugs the block all nucleotide synthesis:
Hydroxyurea, methotrexate, trimethoprim, pyrimethamine
Actinomycin D mechanism of action
inhibits RNA pol
Cause of beriberi
B1 deficiency
Pathogenesis of I-cell disease
defective enzyme in golgi –> can’t phosphorylate mannose –> low mannose-6-P –> enzymes are secreted instead of trafficked to lysosome –> build up of debris in lysosomes
Rate limiting enzyme of TCA cycle
isocitrate dehydrogenase
Vitamin B9
folate
RNA pol III makes
tRNA
Antimycin A target
ETC complex III
Digoxin mechanism
blocking Na-K-ATPase –> decreased Na/Ca exchange –> increased intracellular Ca –> increased contractility
Lack of tyrosinase causes
albinism
Gowers sign
Use of upper extremities to help stand up (common in muscular dystrophies)
Rate limiting enzyme of urea cycle
Carbamoyl phosphate synthetase I
Rett syndrome
MECP2 mutations, only seen in females, “regression”
Menkes disease pathophysiology
Impaired copper absorption due to defective ATP7A –> defective collagen cross-linking –> brittle hair, dev delay, increased risk of aneurysms
Mutation in Li-Fraumeni syndrome
p53
Rate limiting enzyme of glycolysis
PFK-1
Krabbe disease presentation
peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy, globoid cells
Collagen hydroxylation requires
Vitamin C
Urea cycle
Ordinarily Careless Crappers Are Also Frivolous About Urination
Ornithine + Carbamoyl Phosphate –> Citruline + Aspartate –> Arginosuccinate –> Funarate and Arginine –> Urea and Ornithine
Tryptophan is a precursor for
serotonin and niacin
RNA pol II makes
mRNA
Symptoms of Pellagra
3Ds: diarrhea, dementia, and dermatitis
Tay-Sachs presentation
Cherry red spot on macula, NO hepatosplenomegally, progressive neurodegeneration
Becker’s muscular dystrophy
less severe than Duchenne, cause by a non-frameshift deletion –> partially functional
skeletal muscle glycogen phosphorylase deficiency
McArdle disease
Cori Cycle
Glucose from liver to muscle
Lactate from muscle to liver
Tay-Sachs disease
Hexoamidase A loss –> GM2 ganglioside accumulation
Zellweger syndrome presentation
hypotonia, seizures, hepatomegaly, early death
Rate limiting enzyme of ketogensis
HMG-CoA synthase
Signal recognition particle
traffics proteins to rough ER
LDL apolipoproteins
Apo-B 100
Presentation of I-cell disease
coarse facial features, gingival hyperplasia, corneal clouding, restricted hand movements, claw hand, kyphoscoliosis
often fatal in childhood
Vitamin B7
biotine
Duchenne Muscular Dystrophy presentation
progressive weakness beginning in pelvic girdle, calf pseudohypertrophy, waddling gait
Drugs that target ETC complex IV
Azide, cyanide, CO
Debranching enzyme deficency
Cori disease
Is heterochromatin expressed?
No - HC is for highly condensed
Test for lactase deficiency
low pH in stool and H+ on breath
Edward syndrome cause
trisomy 18
Effects of PTH
increased 1,25 D3 production
increased Ca reabsorption in kidney
decreased PO4 reabsorption in kidney
Vitamin B5
Pantothenic acid –> CoA
Folate deficiency labs
high homocysteine, normal MMA levels
Defined Lyonization
Spontaneous X inactivation by methylation
Cri-du chat syndrome cause
chromosome 5 short arm deletion
PKU findings
intellectual disability, microcephaly, seizures, hypopigmented skin, eczema, musty body odor
Down syndrome findings
Intellectual disability, flat facies, single palmar crease, duodenal atresia, Hirschsprung disease, congenital heart disease, early onset alzheimers
Glycogen storage diseases in order I-V:
Vice Presidents Can’t Accept Money: Von Gierke, Pompe, Cori, Andersen, McArdle
Cystinuria pathophysiology
PCT and intestinal deffect preventing reabsorption of COLA: cystine, ornithine, lysine, and arginine
phenylalanine and tyrosine are precursors for
catecholamines
Niemann-Pick disease presentation
progressive neurodegeneration, hepatosplenomegally, cherry red spot on macular, foam cells
Rate limiting enzyme of de novo purine synthesis
glutamine-PRPP amidotransferase
Refsum disease treatment
diet
sorbitol can accumulate in
Lens, Retina, Kidney, Schwann cells ( all lack sorbitol dehydrogenase)
deficient enzyme in Bloom Syndrome
DNA helicase (BLM gene)
F-1,6-BP regulation
activates PFK 1
produced in fed state by PFK 2
converted back to F6P by FBPase2 in fasting state
fragile X presentation (>200 repeats)
macroorchidism, long face, large jaw and ears, autism, mitral valve prolapse, hypermobile joints
Fragile X-syndrome cause
trinucleotide CGC repeat expansion in FMR1 –> decreased expression
tRNA structure
ACC attachment site at 3’
T arm Tethers to ribosome
Anticodon loop
D arm binds synthetase for charging
Niemann-Pick disease
sphingomyelinase loss
Relationship b/w Vitamin C and Fe
C reduces iron to 2+ state –> aids absorption and is ancillary treatment for methemoglobinemia
Prader-Willi presentation
Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia
Apo-A I function
activates LCAT, is found only on HDL
Friedreich ataxia cause
AR trinucleotide expansion of GAA
Hunters see clearly and aim for the X
Hunters syndrome has no corneal clouding and is X linked
RNA pol I makes
rRNA
Excess vitamin A (chronic)
alopecia, dry skin, liver toxicity, increased ICP
alpha1-antitrypsin deficiency pathophysiology
decreased alpha1-AT –> unopposed elastase activity –> breakdown of elastic structures –> COPD
Pyruvate dehydrogenase complex is activated by
High NAD/NADH, high ADP, high Ca
Vitamin B6
pyridoxine
Purely ketogenic amino acids
Leucine, lysine
Prader-Willi syndrome mechanism
Maternal genes are silenced, disease when paternal copy is lost
Cahill Cycle
Alanine from muscle to liver
Glucose from liver to muscle
Glucose-6-phosphate deficiency
Von Gierke disease
Defective in Alport syndrome
Collagen type IV –> BM
Branching enzyme deficiency
Andersen disease
B12 deficiency causes
megaloblastic anemia and subacute combined degeneration (all 3 spinal tracts)
Chylomicron apolipoproteins
Apo-E, C II, and B 48
Essential amino acids
PVT TIM HaLL: phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, leucine, lysine
Patau syndrome cause
trisomy 13
Osteogenesis Imperfecta presentation
BITE: Bones, I(eye - blue sclera), teeth, ear
Hurler and Hunter syndrome
Mucopolysaccharidoses
Kartegener syndrome findings
situs inversus, hearing loss, recurrent infections, infertility
decreased nasal NO is used to screen
Edward syndrome finidngs
PRINCE: Prominent occiput, rocker-bottom feet, Intellectual disability, non-disjunction, ears are low set
death by age 1
Muscular dystrophy inheritance
X-linked
most common urea cycle disorder
Ornithine transcarbamylase deficiency
Cause of Wernicke-Korsakoff syndrome
B1 deficiency –> glucose infusion –> damage to medial dorsal nucleus of thalamus and mamillary bodies
Oligomycin target
ETC complex V
B2 (riboflavin) deficiency
Chielosis, “magenta” tongue, corneal vascularization
Treatment of acute promyelocytic leukemia
all-trans retinoic acid
Williams syndrome cause
microdeletion on chromosome 7 –> “elfin” facies
Fabry disease presentation
triad of episodic peripheral neuropathy, angiokeratomas, and hypohidrosis
Name the purines
Adenine and guanine
Myotonic dystrophy pathophysiology
CTG repeat expansion in DMPK gene –> onset 20-30 years –> CTG: cataracts, toupees, gonadal atrophy
Rate limiting enzyme of glycogenolysis
glycogen phosphorylase
Vitamin B1 (thiamine) deficiency
impaired glucose breakdown –> glucose infusion worsens ATP depletion
Cardiomyopathy, hypotonia, exercise intolerance
Pompe disease - Pompe trashes the pump
Vitamin B3
niacin –> NAD+
Colchicine use
karyotyping - arrests cells in metaphase
glucokinase is found in
liver, beta cells
Kinesin transport direction
anterograde
Gaucher disease
Glucocerebrosidase loss
Hartnup Disease
AR deficiency of neutral AA transport –> decreased niacin production –> Pellagra like symptoms
Apo-E function
mediates remnant uptake
Fabry disease
alpha-galactosidase loss –> ceramide trihexoside accumulation
Location of glucose-6-phosphotase
smooth ER
Apo-B 100
originates in liver, binds LDL receptor
Kartegener syndrome defect
AR dynein arm defect –> immotile cilia
Nissl bodies
rough ER in neurons
Defective in Xeroderma Pigmentostum
Nucleotide Excision Repair
Deficiency in Ataxia-Telangiectasia
Non-homologous end joining
Vitamin B2
Riboflavin –> FAD
Which amino acids are necessary for purine synthesis?
GAG - glycine, aspartate, and glutamine
Dynein transport direction
retrograde
Glugenic and ketogenic amino acids
Isoleucine, phenylalanine, tryptophan, threonine
Ehlers-Danlos syndrome mechanism
faulty collagen synthesis
Vitamin B12
cobalamin
Apo-B 48
originates in intestines, mediates chylomicron secretion
Cardiac glycoside (digoxin) target
Na-K-ATPase
Marasmus
Malnutrition not causing edema
Osteogenesis Imperfecta defect
Collagen glycosylation (usually AD)
G6PD deficiency clinical features
x linked, bite cells and heinz bodies
HDL apoliproteins
Apo-E, A I, C II
Drugs that block purine synthesis:
G-MP, mycophenylate, and ribavirin
B6 (pyroxidine) deficiency
convulsions, hyper-irritability, peripheral neuropathy, sideroblastic anemia
When does nucleotide excision repair occur
G1
Aspiring overdose
disrupts mithocondrial membrane –> no electron transport
Hyperammonemia presentation
flapping tremor, slurring speech, vomiting, cerebral edema, blurred vision
substances that metabolize to propionyl-CoA
VOMIT: valine, odd chain fatty acids, methionine, isoleucine, threonine
Cause of Maple Syrup Urine disease
blocked degradation of Isoleucine, leucine, and valine (B1 loss) –> increased alpha-keto acids in blood.
Vitamin B1
thiamine
Ornithine transcarbamylase deficiency presentation
increased orotic acid, symtpoms of hyperammonemia
Rate limiting enzyme of gluconeogenesis
F-1,6-BP1
Andersen disease presentation
hepatosplenomegaly and failure to thrive
Rate limiting enzyme of HMP shunt
G6PD
Gaucher disease presentation
hepatosplenomegally, pancytopenia, osteoporosis, avascular necrosis of femur head, Gaucher cells
Krabbe disease
Glacatocerebrosidase loss
Angelman syndrome presenation
SAIL: seizures, ataxia, Intellectual disability, (inappropriate) laughter
Zellweger syndrome defect
AR disorder of peroxisomes
Fragile X presentation (<200 repeats)
tremor, ataxia, primary ovarian insufficency
Hyperammonemia treatment
- Lactulose to acidify GI and trap NH4
- Abx if bacterial cause
- Benzoate, phenylacetate or phenylbutyrate to increase glycine and glutamine excretion
Increased glycogen in muscle that can’t be broken down causing painful cramps and myoglobinuria (red urine)
McArdle disease
Excess vitamin A (acute)
nausea, vomiting, increased ICP
Metachromatic leukodystrophy
Arylsulfatase A loss –> cerebroside sulfate accumulation
Rate limiting enzyme of glycogenesis
glycogen synthase
three ketone bodies
acetone, acetoacetate, beta-hydroxybutyrate
Rate limiting enzyme of fatty acid oxidation
Carnitine acyl transferase
Ragged red muscle fibers
mitochondrial myopathy
Kwashiorkor presentation
MEALS: malnutrition, edema, anemia, liver is fatty, skin lesions
Weird cause of B7 (biotin) deficiency
excessive consumption of egg white
Cori disease presentation
like Von Gierke, but mild and normal blood lactate. Gluconeogenesis is intact.
PKU is caused by
lack of phenylalanine hydroxylase
McCune-Albright syndrome defect
G_s-protein activating mutation, lethal unless mosaic
Marfan defect
Fibrillin 1
Down syndrome cause
trisomy 21
alkaptonuria is caused by
lack of homogentisate oxidase
Na-K-ATPase function
2 K in, 3 Na out
Alkaptonuria findings
pigment forming homogentisic acid builds up in tissues –> blue-black CT, ears, sclera; urine oxidizes black
McCune-Albright syndrome presentation
unilateral cafe-au-lait spots with ragged edges, bone is replaced by collagen and fibroblasts, endocrinopathy
Hereditary fructose intolerance is caused by
deficiency of Aldolase B
Drugs that inhibit ETC complex I
Rotenone, metformin
Defective in Lynch Syndrome (HNPCC)
Mismatch repair
Hardy-Weinberg equation
p^2 + 2pq + q^2 = 1
