Diseases Flashcards
Myasthenia Gravis
Antibodies block Ach (breakdown in communication between nerves and muscles)
Symptoms: muscle weakness, double vision, fatigue
Treatment: acetylcholinesterase inhibitors (physostigmine)
Lead poisoning
Pb (Lead) inhibits delta-aminolevulinic acid dehydratase (ALAD)
Symptoms: abdominal pain, sideroblastic anemia, headache, irritability
Treatment: Ca-EDTA w/ dimercaprol (Pb has a higher affinity for EDTA than Ca 2+, Pb binds to EDTA and is then excreted in urine). Children can use succimer
Fanconi-Bickel syndrom (jekyll-Hyde)
GLUT2 deficiency in liver, pancreatic B cells, proximal renal tubules. Autosomal recessive
Affects: Hepatomegaly (enlargement of liver), stunted growth, failure to thrive
Symptoms: hyperglycemia postprandial (post meal), hypoglycemia between meals, serum insulin normal (B cells fail to sense increase in glucose)
Treatment: Small frequent meals, electrolytes, Vit D/phosphate supplements
Drug-induced lupus erythematosus
Mutations in enzymes that carry out acetylation (how body metabolizes drugs)
Affects: slow rate of drug acetylation. Drugs concerted to toxic by-products and this triggers antibodies
Symptoms: Muscle and bone pain, rashes, inflammation of lungs and heart, fever, fatigue
Treatment: NSAIDs, wait for effects to wear off
Niemann-Pick disease
Think liPid…Pick…
Harmful quantities of lipids accumulate in the spleen, liver, lungs, bone marrow, and the brain.
Affects: deficiency in sphingomyelinase (sphingomyelin accumulates in lysosomes)
Symptoms may include lack of muscle coordination, neurologic damage (mental retardation, seizures, ataxia (loss of body control) spasticity (muscle tightness), enlarged liver and spleen, cherry red spot in eye
Treatment: none
Spur cell anemia
Elevated cholesterol in erythrocyte membrane
Symptoms: rigid RBC’s break!
Treatments: associated w/ beta lipoproteinemia and advanced stages of alcoholic cirrhosis (chronic liver damage leading to scarring and failure)
Cystinuria
Defect in transporters for cystine (not Cysteine-2 cysteine=cystine), ornithine, lysine, and arginina (COLA). Autosomal recessive
Affects: forms cystine crystals in kidneys (kidney stones)
Symptoms: Renal colic (waves of abdominal pain), identified by + nitroprusside test
Hartnup disease
(“Trypping” infants)
Defect in transporters for nonpolar/neutral AA (tryptophan). Autosomal recessive
Affects: infancy
Symptoms: failure to thrive, nystagmus (involuntary eye movement), intermittent ataxia, tremor, photosensitivity
Cystic Fibrosis
Defective Cl- transport, autosomal recessive. Defective CFTR causes buildup of Cl- (and salt) in airway followed by water. Mucus secretions are usually thin become thick
Symptoms: bacterial infections, cough
Treatment: antibiotics
Peroxisome biogenesis disorders (Zellweger spectrum)
Defect in 1 of 12 genes responsible for peroxisome assembly. Zellweger Syndrome is the worst disorder on the spectrum
Affects: affects synthesis of peroxisomes, peroxisomes are thus not present. They are present at birth and fatal within the first year
Symptoms: hypotonia (weak muscle tone), hearing loss, vision loss, feeding problems, seizures, problems caused by breakdown of myelin (insulates nerve fibers in brain)
Lysosomal storage disorders
Lysosomes lack a necessary enzyme and can’t break down material in cell, it builds up and kills cell.
Familial hypercholesterolemia (type 2a/2b)
LDL receptor is completely (2a) or partially (2b) defective
Cholesterol, LDL=increased. Triacylglycerol normal (2a), increased (2b), VLDL increased (2b)
Symptoms: Atherosclerosis. Early MI (as young as 20)
Maple Syrup Urine Disease
(hungry lumberjacks)
Branched chain α-ketoacid dehydrogenase (BCKD). Same coenzymes as PDC. Autosomal recessive
Toxic levels accumulate in blood. Damage brain, mental retardation
Symptoms: Smell of burnt maple sugar in urine
Treatment: synthetic diet w/ limited BCAA’s. W/ mild forms: supplement cofactors (esp. thiamine–>TPP)
Homocystinuria/hyperhomocysteinemia
1) Homocysteine methyltransferase: deficiency B6, B12, folic acid
2) Cystathionine B-synthase: genetic defect
Affects: 1) Homocysteine–>affects metabolism of Met (using THF)
2) Homocysteine–>cystathionine
Symptoms: Atherosclerotic heart disease and stroke
Eye lens dislocation, osteoporosis, mental retardation
Treatment: Vitamin supplementation might help
Tyr–>dopa–>dopamine–>norepinephrine–>epinephrine
Tyrosinase deficiency prevents–> melanin (albinism)
MAO and COMT degrade catecholamines into HVA and VMA (can be diagnostic of pheochromocytoma-tumor of adrenal medulla)
Thyroglobulin (made by follicular cells of thyroid gland), contains about 120 Tyr residues
Tyr–>thyroglobulin
Thyroglobulin helps make T3, T4
Acetaminophen detox/Glutathione
GSH (glutathione) helps protect RBC’s
Acetaminophen overdose decreases GSH. Leads to increased GGT, marker for atherosclerotic cardiovascular disease (CVD)
Carbamoyl phosphate synthetase II (cytosolic)
First step de novo pyrimidines.
Stimulated by PRPP
Inhibited by UTP
Cytosolic carbamoyl phosphate–>orotic acid–>UMP
Defect in UMP synthase can lead to orotic aciduria
Sulfa drugs
Inhibits bacterial enzyme from converting PABA–>Folate, which disrupts DNA replication
Doesn’t affect humans b/c we don’t get folate in diet
Methotrexate
Dihydrofolate reductase (converts dietary folate to active tetrahydrofolate in liver)
Methotrexate inhibits DHF reductase
Inhibits DNA (target: cancer)
Severe combined immunodeficiency (SCID)
“bubble boy”
Adenosine deaminase (ADA) deficiency. Excess ADA–>hemolytic anemia-destroying RBC’s (so it’s a “goldilocks” amount)
High levels adenosine–>AMP/ADP–>dATP–>inhibits ribonucleotide reductase
Symptoms: B and T cells crippled
Gout
Build-up of uric acid in blood.
Primary hyperuricemia-overproduction of uric acid
Secondary hyperuricemia-underexcretion of uric acid
Painful joints and kidney damage due to sodium urate deposits
Treatment: allopurinol: blocks xanthine oxidase
Colchicine: blocks inflammatory response from “attacking” sodium urate crystals in joints
Avoid high purine diet (meat, seafood, alcohol)
Lesch-Nyhan syndrom
No HGPRT
Effects: Hypoxanthine–> IMP
Guanosine–>GMP
Not possible
Symptoms: x-linked PRPP increase. Severe gout: self-mutilation, mental retardation
Acyclovir
Anti-viral drug
Thymidine kinase phosphorylates Acyclovir
Effects: Undergoes phosphorylation by viral thymidine kinase to acyclo GMP–>acyclo GTP. It lacks 3’ OH, leads to termination of DNA replication
Promotes the healing of sores produced by chickenpox, shingles, genital herpes
Diabetes mellitus (diabetes)
Type 1: decreased insulin output by pancreas
Type 2: decreased insulin sensitivity by target tissues (strongly associated w/ obesity)
Effects: Fasting glucose level >120 mg/gL is indicative of diabetes
Symptoms: polyuria, polydipsia, heart disease, stroke, blindness, kidney dysfunction, etc
Treatment: Insulin injections
PPP G6P deficiency
G6PD reduces NADP+ to NADPH which then is used to reduce glutathione. Glutathione helps to maintain RBC membrane integrity by getting rid of ROS. W/o glutathione, RBC membranes break
Symptoms: hemolytic anemia
Von Gierke disease and GSD 1B
- Von Gierke disease (GSD 1A)-autosomal recessive
- Glucose 6 phosphatase deficiency (inside SER lumen)
- GSD 1B: defective transport protein that moves G6P into SER lumen
Effects: Both-free glucose not released into blood
Symptoms: Both-hypoglycemia while fasting, lactic acidosis, hepatomegaly, hyperlipidemia
Treatment: liver transplant or surgical transposition of hepatic portal vein
Eating uncooked cornstarch before bed
Pyruvate dehydrogenase deficiency
X linked, generally related to E1 subunit of PDC
Effects: Male infants
Symptoms: increased serum pyruvate and lactate levels, neonatal lactic acidosis
Treatment: B1, lipoid acid, biotin supplements (biotin serves as cofactor for pyruvate carboxylase)
- Dichloroacetate-PDK inhibitor
- Ketogenic diet to minimize pyruvate formation (ketogenic AA’s Lys and Leu can be used to form acetyl-CoA thus bypassing PDC)
Beriberi (dry)
Thiamine (B1) deficiency
Affects cardiovascular function (blood test for thiamine levels). OFten seen in alcoholics b/c alcohol inhibits thiamine absorption–>Wernicke-Korsakoff
Symptoms: Weight loss, shortness of breath, difficulty walking, mental confusion, lack of coordination
Thiamine supplementation, other water-soluble vitamins
Wernicke-Korsakoff Syndrome (wet)
Thiamine pyrophosphate (cofactor for alpha-ketoglutarate dehydrogenase)
Thiamine deficiency caused by ethanol inhibiting its absorption
Increased blood levels of pyruvate and alpha-ketoglutarate b/c of impaired PDC and alpha-ketoglutarate dehydrogenase which requires thiamine pyrophosphate as cofactor
Treatment: Thiamine supplementation, other water-soluble vitamins
Pyruvate decarboxylase deficiency
More pyruvate–>lactic acid (rather than oxaloacetate)
Autosomal recessive
Effects: Lactic acid high in blood
Symptoms: In infancy, seizures, hypotonia, ataxia
Acid-Base balance and the kidneys
Kidneys regulate blood pH. They can remove H+ in form of NH4+ (ammonium) and reabsorb bicarbonate (HCO3-).
Biological oxidation
Biological oxidation provides most the energy for aerobic metabolism.
Diabetic ketoacidosis
Marked by hyperglycemia and low blood pH, leads to uncontrolled diabetes. Lack of insulin prevents glucose being taken up by cells to make energy. The body starts degrading FA’s for energy and this generates ketone bodies (which lower blood pH). Symptoms: dehydration, vomiting, confusion, coma.
Treatment: insulin and fluids
Catalytic triad in serine proteases, includes which AA’s?
His, Asp, Ser (HAS)
Enteropeptidase activates trypsin from trypsinogen.
.
Inhibition of metalloenzymes
Metalloenzymes (enzymes that require metal cofactors, i.e. Mg 2+ and Zn 2+) are inhibited by chelating agents that bind and remove these metals. An example=ethylenediaminetetraacetic acid (EDTA) inhibits metalloenzymes
Troponin in myocardial infarction
Calcium binds to troponin and changes its conformation. This is transmitted to tropomyosin and then allows myosin to bind to actin filaments and then allows muscle contraction.
Enzymes useful for medical diagnoses
Bone disease: alkaline phosphatase
Obstructive liver disease: sorbitol dehydrogenase or lactate dehydrogenase (LDH-5)
Prostatic cancer: acid phosphatase
Acute pancreatitis: amylase
Muscular dystrophy: AST
Liver disorder: ALT
Irreversible steps in glycolysis:
Glucose–>G6P (hexokinase)
F6P–>F1,6bP (phosphofructokinase)
Phosphoenolpyruvate–>pyruvate (pyruvate kinase)
Gluconeogenesis- bypass step enzymes
PEP carboxykinase pyruvate carboxylase
Fructose 1,6-bisphosphatase
Glucose 6-phosphatase
Pentose phosphate pathway
Causes hemolytic anemia b/c of deficient levels of NADPH in red cells
Depriving cells of GMP and dGTP
The oxidation step when converting IMP to XMP allows for therapeutic intervention. Enzyme is IMP dehydrogenase is targeted by drugs such as the immunosuppressant Mycophenolic acid and this disrupts DNA replication in B and T cells by by depriving cells of needed dGTP. Helps prevent graft rejection
Nitrogen balance
+ balance when growing
- balance=malnutrition
BUN test (blood, urea, nitrogen)
Aminotransferases in clinical setting
AST=liver disease. Elevated in later stages of disease
AST=muscle
Tetrahydrobiopterin (THB)/dihydrobiopterin
THB is cofactor in hydroxylations of aromatic amino acids and in making NO.
THB is made from GTP and regenerated by NADPH. Not having enough THB leads to PKU (also less dopamine, norepinephrine and serotonin).
Patients w/ hyperthyroidism disorders (Graves disease) are treated w/:
carbimazole and propylthiouracil
Creatine
Presence of cardioselective isoform of creatine kinase (CK-MB) in serum is diagnostic of myocardial infarction (MI) (peaks 10-24 hrs after MI)
Carbamoyl phosphate synthetase
Used in de novo synthesis of pyrimidines. Orotic acid is intermediate in pathway for making UMP. A defect in UMP synthase leads to orotic acid–>orotic aciduria. (not accompanied by hyperammonemia or a reduction in BUN levels)
Cardiotonic drugs
Ouabain and digoxin are contraction inducing/cardiotonic drugs
Inhibit Na+/K+ ATPase on cardiac myocytes. Lead to increase in intracellular Na+ and increase in Ca 2+ b/c of slowing of NCX (Na-Ca exchanger)
More Ca results in stronger contraction
