Biochemistry Flashcards
De Novo pyrimidine and purine synthesis
67FA
Lesh-Nyhan Syndrome
HGPRT enzyme (Hyperuricemia, Gout, Pissed off, Retardation, Dystonia). Rx - Allopurinol or febuxostat
Purine salvage
Adenosine deaminase deficiency
Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide redcutase which prevents DNA synthesis and thus decreases lymphocyte count. (SCIDs)
Single stranded binding proteins
prevents strands from reannealing
DNA polymerase III
Prokaryotic only - Elongates leading strand by adding deoxynucleotides to the 3’ end. Elongates lagging strand until it reaches primer of preceeding fragment. 3’->5’ exonuclease activty. 5’->3’ synthesis
DNA polymerase I
Prokaryotic only. Degrades RNA primer; replaces it with DNA. 5’->3’ exonuclease activity
mRNA stop codons
UGA, UAA, UAG
Drugs that act on microtubles
“Microtubles Get Constructed Very Poorly”
Mebendazole (anti-helminth), Griseofulvin (anti-fungal), Colchicine (anti-gout), Vincristine/Vinblastine (anti-cancer), Paclitaxel (anti-cancer)
Collagen types
I (bone, skin, tendon) - Osteogenesis imperfecta
II (cartilage, vitreous body, nucleus pulposus)
III (Reticulum - skin, blood vessels, uterus, fetal tissue) Vascular Ehlers Danlos
IV (Basement membrane) Alport syndrome, Goodpasture syndrome
Osteogenesis imperfecta
Collagen glycosylation problem
Ehlers-Danlos
Collagen cross-linking problem
Menkes disease
Copper (lysyl oxidase). Brittle “kinky” hair, growth retardation, and hypotonia
Elastin
Marfan (fibrillin), Empyhesema (alpha1 antitrypsin)
Blotting procedures
SNoW DroP
Southern - DNA; Northern - RNA; Western - Protein
Indirect ELISA
uses a test antigen to see if a specific antibody is present in the patient’s blood
Direct ELISA
Uses a test antibody to see if a specific antigen is present in the patient’s blood; a secondary antibody coupled to a color-generating enzyme is added to detect the antigen
Prader-Willi syndrom
Maternal imprinitng. Hyperphagia, obesity, intellecutal disability, hypogonadism, and hypotonia.
Angelman syndrom
Paternal imprinting. Results in inappropriate laughter, seizures, ataxia, and severe intellectual disability.
Myeloperoxidase
Blue-green based pigmented molecule contained within the azurophilic granules of neutrophiles that catalyzes the production of hypochlorus acid (HOCl) from chloride and hydrogen peroxide during the phagocytic respiratory burst. Neutrophil myeloperoxidase is responsible for the green color of pus and sputum in bacterial infections.
MAP kinase
Growth factor receptors (EGF, PDGF, FGF)
JAK/STAT
Receptors for cytokines, growth hormone, prolactin, IL-2
Autosomal Dominant diseases
ADPKD, FAP, Familial hypercholesterolemia, hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome), hereditary spherocytosis, Huntington disease, Marfan syndrome, Multiple endocrine neoplasias, NF1, NF2, Tuberous Sclerosis, von Hippel-Linadau disease (chromosome 3)
Autosomal Recessive
Albinism, ARPKD, cystic fibrosis, glycogen storage diseases, hemochromatosis, Kartagener syndrome, mucopolysaccharidoses (except hunter syndrome), PKU, sickle cell anemia, sphingolipidoses (except Fabry disease), thalassemias, Wilson disease
CFTR gene
chromosome 7
X-linked recessive disorders
“Be Wise, Fool’s GOLD Heeds Silly HOpe”
Bruton agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne (and Becker) muscular dystrophy, Hunter syndrome, Haemophilus A&B, Ornithine transcarbamylase deficiency
Tuberous sclerosis
Neurocutaneous disorder with multi-organ system involvement, characterized by numerous benign hamartomas. Incomplete penetrance, variable expression.
Trinucleotide repeat expansion diseases
Huntington disease (CAG); Fragile X syndrome (CGG); Freidereich ataxia (GAA), Myotonic dystrophy (CTG)
Trisomy screening results
See notes
Robertsonian translocation
13,14,15,21, and 22
Asymptomatic or Down Syndrome/Patau
22q11 deletion syndromes
“CATCH-22”
Cleft palate, Abnormal facies, Thymic aplasia ->T-cell defiency, Cardiac dfects, Hypocalcemia secondary to parathryoid aplasia, due to microdeletion at chromosome 22q11
DiGeorge syndrome - tymic, parathryoid, and cardiac defects
Velocardiofacial syndrome - palate, facial, and cardiac defects
Water soluble vitamins
B1 - Tiamine ; TPP
B2 - riboflavin; FAD, FMN
B3 - niacin ; NAD+
B5 - pantothenic acid ; CoA
B6 - pyridoxine ; PLP
B7 - biotine
B9 - folate
B12 - cobalamin
C - Ascorbic acid
Alcohol breakdown
Fomepizole inhibits alcohol dehydrogenase (cytosol)
Disulfiram inhibits acetaldehyde dehyrdrogenase (mito)
Rate determining enzymes of metabolic processes
FA 99
Essential Amino Acids
Glucogenic (methioniine, valine, histidine)
Glucogenic/ketogenic (isoleucine, phenylalanine, threonine, tryptophan)
Ketogenic (leucine, lysine)
Phenylalaine derivatives
Phenylalanin -> Tyrosine ->Dopa->Dopamine->NE->Epi
BH4, BH4, B6, Vit C, SAM
Also - Tyrosine -> Thyroxine; Dopa -> Melanin
Tryptophan derivatives
Tryptophan ->Niacin-> NADP/NAD
B6
Tryp->Serotonin->Melatonin
(BH4, B6)
Histadine derivatives
Histidine ->Histamine
B6
Glycine derivatives
Glycine->Porphyrin->Heme
B6
Glutamate derivatives
Glutamate ->GABA (B6)
Glutamate ->Glutathion
Arginine derivatives
Creatinine, Urea, NO
(BH4)
Essential fructosuria
Involves a defect in fructokinase. Autosomal recessive. A benign, asymptomatic condition, since fructose is not trapped in cells. Symptoms: frcutose appears in blood and urine. Disorders of fructose metabolism cause milder symptoms than analogous disorders of galactose metabolism.
Fructose intolerance
Hereditary deficiency of aldolase B. Autosomal recessive. Fructose-1-P accumulates, causing a decrease in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis. Symptoms present following consumption of fruit, juice, or honey. Urine dipstick will be negative (tests for glucose only); reducing sugar can be detected in the urine (nonspecific teswt for inborn errors of carbohydrate metabolism). Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting. Treatment: decrease intake of both fructose and sucrose (glucose + fructose).
FA 106
Galactokinase deficiency
Hereditary deficiency of glactokinase. Galacititol accumulates if galactose is present in diet. Relatively mild condition. Autosomal recessive. Symptoms: galactose appears in blood and urine, infantile cataracts. May initially present as failure to track objects or to develop a social smile.
Classic galactosemia
Absence of galactose-1-phosphate uridyltransferase. Autosomal recessive. Damage is caused by accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye). Symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability. Treatment: exclude galactose and lactose (galactose + glucose) from diet. Can lead to PO4 depletion and E. coli sepsis in neonates.
Galactose metabolism
Sorbitol pathway
FA 107
Urea cycle
FA 108
Ammonia intoxication
tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
Catecholamine synthesis
PKU
due to decrease phenylalanine hydroxylase or decrease tetrahydrobiopterin cofactor (malignant PKU). Tyrosine becomes essential. increase phenylalanine leads to excess phenylketones in urine. Findings: intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor. Treatment: decrease pheynylaline and increase tyrosine in diet.
Maternal PKU
lack of proper dietary therapy during pregnancy. Finding in infant: microcephaly, intellectual disability, growth retardation, congenital heart defects
Alkaptonuria (ochronosis)
Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate. Autosomal recessive. Benign disease. Findings: dark connective tissue, brown pigmented sclerae, urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage)
Homocystinuria
Types (all autosomal recessive): Cystathionine synthase deficiency (treatment: decrease methionine, inc cysteine, inc B12, and folate in diet); dec affinity of cystationine synthase for pyridoxal phosphate (treatment: inc inc B6 and inc cysteine in diet); Homocysteine methyltransferase (methionine synthase) deficiency (treatment: inc methionine in diet)
All forms result in excess homocysteine. Findings: increase homocysteine in urine, intellectual disability, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), thrombosis, and atherosclerosis (stroke and MI).
FA 111
Cystinuria
Hereditary defect of renal PCT and intestinal amino acid transporter for Cysteine, Ornithine, Lysine, and Arginine (COLA). Excess cystine in the urine can lead to precipiation of hexagonal cystine stones. Autosomal recessive (common). Urinary cyanide-nitroprusside test is diagnostic. Treatment: urinary alkalinization (e.g., potassium citrate, acetazolamide) and chelating agents inc solubility of cystine stones; good hydration. Cystine is made of 2 cysteins connected by a disulfide bond.
Maple syrup urine disease
Blocked degradation of branched amino acids (isoleucine, Leucine, Valine) due to dec alpha-ketoacid dehydrogenase. Causes inc alpha-ketoacids in the blood, especially those of leucine. Causes severe CNS dfects, intellectual disability, and death. Autosomal recessive. Urine smells like maple syrup/burnt sugar. Treatment: restriction of leucine, isoleucine, and valine in diet, and tiamine supplementation.
Glycogen storage diseases
FA 113
Lysosomal storage diseases
FA 114
Carnitine deficiency
inability to transport LCFAs into the mitochondria, resulting in toxic accumulation. Causes weakness, hypotonia, and hypoketotic hypoglycemia.
Nuclear localization signals
4-8 AA (lysine, arginine and proline
G1->S
Cyclin E/CDK2
Cyclin D/CDK4
G2->M
Cyclin A/CDK2 complex (mitotic prophase)
Cyclin B/CDK1 complex activated by cdc 25
Cell membrane phospholipids
draw diagram of cox pathway
IL-1
Macrophages. increase neutrophil and macrophage migration, inc acute phase reactants, fever and shock
IL-2
T-cells. inc T-cell activation and proliferation, inc NK cell and macrophage activity, inc B-cell growth
IL-3
T-cells. inc hematopoiesis
IL-4
TH2 cells. inc TH2 cell differentiation, inc B cell growth, inc isotype switching to IgA
IL-5
TH2 cells. Inc differentiation of eosinophils, inc isotype switching to IgA?
IL-6
Macrophages. Inc T and B cell growth, inc osteoclast activity, inc acute phase reactants and fever
IL-8
Macrophages, T-cells. Inc neutrophil activation and chemotaxis
IL-10
TH2 cells. dec TH1 cell differentation, dec cell mediated immunity and APC activity, inc B cell function
IFNg
TH1 cells, NK cells. Inc intracellular killing by macrophages, inc MHC class I and II expression, inc TH1 cell differentation
TGFb
Mast cell types. Dec immune cell function, inc matrix synthesis and angiogenesis
GM-CSF
T-cells, Macrophages. Inc growth and differentiation of myeloid progenitors
TNFa
Macrophages. Inc inflammation and cell-mediated immunity, inc acute phase reactants, fever and schock.
