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27 Cards in this Set
- Front
- Back
Phenylketonuria
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- phenylalanine hydroxylase deficiency
- phenylalanine hydroxylase conversts phenylalanine to tyrosine - tyrosine becomes essential AA and phenylalanine builds up - symptoms: mental retardation, growth retardation, musty body odor - treatment: decrease phenylalanine and increase tyrosine in diet |
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Alkaptonuria
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- homogentisic acid oxidase deficiency
- homogentisic acid oxidase degrades tyrosine - results in black urin, dark connective tissue and joint pain |
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Albinism
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- deficiency in tyrosinase (makes melanin from tyrosine) or deficiency in tyrosine transporters (decreased amount of tyrosine and thus melanin)
- increased risk of skin cancer |
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Homocystinuria
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- caused by either cystathione synthase deficiency, decreased affinity of cystathione synthase for pyridoxal phosphate, or homocystein methyltransferase deficiency
- results in excess homocysteine and cysteine becomes essential - causes mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation and atherosclerosis |
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Cystinuria
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- common inherited defect of renal tubular amino acid transporter for cystein, ornithine, lysine and arginine in the PCT of the kidneys
- excess cystine in urine can lied to precipitation as cystine kidney stones (cystine is made of 2 cysteines connected by a disulfide bond) |
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Maple syrup urine disease
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- blocked degradation of branched AAs (Ile, Val, Leu) due to decreased alpha-ketoacid dehydrogenase
- causes increased alpha-ketoacids in the blood, especially Leu - causes severe CNS defects, mental retardation and death - urine smells like maple syrup - I Love Vermont maple syrup |
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Purine salvage deficiencies
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- adenosine deaminase deficiency
- can cause SCID - excess ATP and dATP imbalances nucleotide pool via feeback inhibition of ribonucleotide reductase (preventing DNA synthesis and thusly decreased lymphocyte count) - Lesh-Nyhan syndrome - HGPRT deficiency (converts hypoxanthine to IMP and guanine to GMP) causing excess uric acid production (because purines cannot be salvaged) - symptoms: retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis - HGPRT: He's Got Purine Recovery Trouble |
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Fasting and starvation
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- Days 1-3
1. hepatic glycogenolyis and glucose release 2. adipose release of FFA 3. muscle and liver shifting fuel use from glucose to FFAs 4. hepatic gluconeogenesis - After Day 3 muscle protein loss is maintained by hepatic formation of ketone bodies, supplying the brain and heart - After several weeks ketone bodies become main source of energy for brain, so less muscle protein is degraded than during days 1-3. after fat stores are depleted, vital protein degradation accelerates, leading to organ failure and death |
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Insulin
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- made in beta cells of pancreas in response to ATP from glucose metabolism acting on K+ channels and depolarizing cells (required for adipose and skeletal muscle uptake of glucose)
- GLUT2 receptors are found in beta cells and GLUT4 in muscle/fat (GLUT1 in brain/RBCs) - insulin inhibits glucagon release by alpha cells of pancreas - serum C-peptide is not present with exogenous insulin intake (proinsulin --> insulin + C-peptide) |
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Glycogen
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- branches have alpha-1,6 and linkages have alpha-1,4 bonds
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Glycogen storage diseases
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- Von Gierke's disease: glucose-6-phosphatase deficiency resulting in fasting hypoglycemia, increased glycogen in liver, increased blood lactate and hypatomegaly
- Pompe's disease: lysosomal alpha-1,4-glucosidase dificiency causing cardiomegaly and systemic findings leading to early death - Cori's disease: debranching enzyme alpha-1,6-glucosidase deficiency causing a milder form of type 1 (VGD)with normal blood lactate levels - McArdle's disease: skeletal muscle glycogen phosphorylase deficiency causing increased glycogen in muscle, but cannot break it down, leading to muscle cramps, myoglobinuria with strenous excersize - Very Poor Carbohydrate Metabolism |
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Gaucher's disease
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- lysosomal storage disease: beta-glucocerebrosidase deficiency (glucocerebroside builds up)
- symptoms: hepatosplenomegaly, aseptic necrosis of femur, bone crisis, Gaucher's cells (macrophages that look like crumpled tissue paper) |
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Tay-Sachs disease
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- lysosomal storage disease: hexosaminidase A deficiency (GM2 ganglioside builds up)
- symptoms: progressive neurodegeneration, developmental delay, cherry red spot (on retina), lysosomes with onion skin |
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Fatty acid metabolism cites
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- citrate shuttle: transports acetyl-CoA from the mitochondrial matrix to the cytoplasm for fatty acid synthesis
- carnitine shuttle: transports acyl-CoA (fatty acid + CoA) into mitochondrial matrix for breakdown (carnitine deficiency leads to an inability to utilize LCFAs and toxic accumulation) |
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Cholesterol synthesis
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- HMG-CoA reductase: rate limiting enzyme, inhibitory target of statins
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Essential fatty acids
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- linoleic and linolenic acids (arachidonic acid, if linoleic acid is absent)
- eicosanoids are dependent of essential fatty acids |
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Lipoproteins (enzymes)
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- Pancreatic lipase––degradation of dietary TG in small intestine.
- Lipoprotein lipase (LPL)––degradation of TG circulating in chylomicrons and VLDLs. - Hepatic TG lipase (HL)––degradation of TG remaining in IDL. - Hormone-sensitive lipase––degradation of TG stored in adipocytes. - Lecithin-cholesterol acyltransferase (LCAT)––catalyzes esterification of cholesterol. - Cholesterol ester transfer protein (CETP)––mediates transfer of cholesterol esters to other lipoprotein particles. |
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Major apolipoproteins
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- A-I: activates LCAT
- B-100: Binds to LDL receptor, mediates VLDL secretion - C-II: cofactor for lipoprotein lipase - B-48: mediates chylomicron secretion - E: mediates extra (remnant) uptake |
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LDL vs HDL
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- LDL transports cholesterol from liver to tissue
- HDL transports cholesterol from periphery to liver - HDL is Healthy, LDL is Lousy |
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Chylomicrons
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- secreted by intestinal epithelial cells
- deliver dietary triglycerids to peripheral tissues - deliver cholesterol to liver in form of chylomicron remnants |
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Lipoproteins
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- VLDL: delivers hepatic triglycerides to peripheral tissues
- IDL: delivers triglycerides and cholesterol to liver, where they are degraded to LDL (IDL is formed in the degeneration of VLDL) - LDL: delivers hepatic cholesterol to peripheral tissues - HDL: mediates centripetal transport of cholesterol (from periphery to liver) |
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Familial dyslipidemias
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- Type I-hyperchylomicronemia: lipoprotein lipase deficiency or altered apolipoprotein C-II causes increased blood levels of chylomicrons (and thusly TG, cholesterol)
- Type IIa-hypercholesterolemia: ↓ LDL receptors cause increased LDL (and thusly cholesterol) in blood - Type IV-hypertriglyceridemia: hepatic overproduction of VLDL causes increased circulating VLDL (and thusly TGs) |
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Porphyrias
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- lead poisoning, acute intermittent porphyria, porphyria cutanea tarda
- symptoms: the 5 P's - Painful abdomen, Pink urine, Polyneuropathy, Psychological distrubances, Precipitated by drugs |
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Heme catabolism
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- Heme → biliverdin → bilirubin
- bilirubin is removed from blood by liver, conjugated with glucuronate and excreted in bile |
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Hemoglobin
(composition, regulation, types) |
- composed of 4 polypeptide subunits (2 α and 2 β)
- T (taut) form has low affinity for O2 - R (relaxed) form has high affinity for O2 - regulation: ↑ Cl−, H+, CO2, 2,3-BPG, and temperature favor T form over R form (shifts dissociation curve to your right, leading to ↑ O2 unloading). - fetal hemoglobin (2α and 2γ) has lower affinity for 2,3-BPG than adult hemaglobin and thus has higher affinity for O2 (allowing it to "steal" O2 from maternal circulation) |
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CO2 transport in blood
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- transported as bicarbonate
- transported by hemoglobin; binds to hemoglobin (not at O2 site) |
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Hemoglobin modifications
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- Methemoglobin: oxidized form of hemoglobin (Fe3+ instead of Fe2+), treated with methylene blue
- carboxyhemoglobin: form of hemoglobin bound to CO in place of O2 (CO has 200x greater affinity than O2 for hemoglobin) |