9/6/17 Flashcards

Question

Accumulation of cholesterol

Answer 1

Intracellular accumulation of cholesterol is common in macrophages in patients with xanthomas, atherosclerosis, and inflammation Xanthomas: fatty deposits under joints, hypercholesterolemia (hyperlipidemia) creates yellowish nodules under tendons of the heel/knee Tissue macrophages actively take up LDL cholesterol and store it, foamy macrophages

Answer 2

Genetic mutation that alters the function of a lysosomal enzyme in a catabolic pathway Accumulation of the substrate or accumulation of degradation intermediaries, which may be toxic to cells Decreased production of the pathway's product

Answer 3

Sphingolipid storage disorder resulting from glucocerebrosidase deficiency Deposition of glucocerbrosides in macrophages in the liver, spleen, lymph nodes, or bone marrow Lipid-laden macrophages look like wrinkled-tissue paper, not foamy appearance

Answer 4

Excess protein reabsorption in renal tubular cells: disorder with heavy protein leakage across glomerulus, tubular cells have increased protein reabsorption Excess Protein Synthesis: excess synthesis of antibodies by plasma (Mott) cells can outpace secretion, creates dilated endosomes called Russell bodies Defective transport and secretion from gene mutation: alpha 1 - antitrypsin deficiency is recessive, misfolded proteins build up in liver ER and not secreted, causes emphysema in lungs Aggregates of cytoskeleton proteins: keratin filaments in alcoholic liver disease, Mallory bodies, also in Alzheimer's Intracellular accumulation of pigments: endogenous and exogenous

Answer 5

Normal blood sugar levels Severe cardiomegaly Glycogen accumulation in lysosomes Normal glycogen structure Recessive, deficiency of alpha-glucosidase in lysosome, converts glycogen to glucose

Answer 6

Lipofuscin: collection of lipids and proteins that can't be metabolized, multiple small golden brown pigment granules in myocytes like in the heart and skeletal muscle, normal wear and tear from cells that are post mitotic or don't divide frequently, due to oxidation and can also impair other degradation pathways Hemosiderin: aggregate of ferritin micelles, yellow brown pigments Accumulates due to higher iron absorption, lower iron use, hemolytic anemia, and transfusions Can be in the liver, use Prussian blue stain

Answer 7

Anthracosis: accumulation of exogenous carbon by alveolar macrophages Common in smokers and urban people, no apparent cell injury Transferred from lungs to lymph nodes Appear as black spots Also tattoos

Answer 8

Null Hypothesis: data are normally distributed P<0.05 means data are NOT normally distributed

Answer 9

Glutathione peroxide reduces hydrogen peroxide, regenerate reduced glutathione via NADPH in glutathione reductase Deficiency of glucose-6-P dehydrogenase (first enzyme in PPP) reduces NADH, reduced glutathione, and integrity of red blood cells RBCs carry oxygen so need antioxidant

Answer 10

Cytoplasm of tissues that need NADPH for FA and steroid synthesis or detoxification Also in RBCs since need glutathione to protect from oxidative damage Adrenal gland, liver, tested, adipose tissue, ovaries, mammary glands, and RBCs

Answer 11

``` 1. Oxidative Phase- Substrate: glucose 6-P and NADP+ Products: NADPH and ribulose 5-P Controlling Enzyme: glucose 6-P dehydrogenase Regulation: inhibition by NADPH ``` ``` 2. Non-Oxidative Phase- Substrate: glyceraldehyde 3-P and Fructose 6-P Products: Ribose 5-P Controlling Enzyme: none Regulation: levels of ribose 5-P ```

Answer 12

1. Glu 6-P oxidized to 6-phosphogluconolactone and makes NADPH Glucose 6-P dehydrogenase (rate limiting), inhibited by NADPH and fatty acyl-CoA 2. Lactone hydrolyzed to 6-phosphogluconate by lactonase 3. 6-phosphogluconate decarboxylated to ribulose 5-P and makes NADPH by 6-phosphogluconate dehydrogenase

Answer 13

Isomerization phase: Ribulose 5-P can isomerize to xyulose 5-P by Ribulose 5-P epimerase or to ribose 5-P by ribulose 5-P isomerase Rearrangement phase: transketolases and transaldolase form 3-7 C sugars, form Fru 6-P and glyceraldehyde 3-P for glycolysis, also form erythrose 4-P for aromatic AAs Transketolases translocates 2 C and transaldolases move 3 C

Answer 14

1. Form 5-phosphoribosyl-pyrophosphate (PRPP) from ribose 5-P via PRPP synthetase using a pyrophosphate from ATP and Mg Activated by inorganic P and inhibited by purine ribonucleotides that are mono or di Used by Salvage and synthesis pathways 2. Synthesis of 5'-phosphoribosylamine from PRPP by removing the PP for an amine, amino from Gln and it turns into Glu, first committed step in purine synthesis since PRPP can become pyrimidine 3. Remaining Steps: add Gly, add carbon from THF, an amine from another Gln, closing first ring, adding carboxyl from CO2, adding Asp, loss of fumarate, another carbon from THF, and closing the second ring to form IMP Overall: 5 ATP, 2 Gln, 1 Gly, 1 CO2, 1 Asp, and 2 formate

Answer 15

AMP: add GTP and Asp for amine then remove fumarate GMP: oxidation to XMP then add amine from Gln (requires PP and gives off Glu) ATP and GTP from monophosphate: use base specific kinase like Adenylate kinase to make 2 ADP from ATP and AMP, next use a nucleoside diphosphate kinase that works for any nucleoside di and triphosphates

Answer 16

When one nucleotide is high it inhibits its formation and stimulates the other to form, ATP stimulates IMP to form GTP and inhibits ATP formation AMP pathway needs GTP and GMP pathway needs ATP so balance purine levels PRPP synthetase inhibited by AMP, ADP, GMP, GDP, and IMP while it's activated by PP Second enzyme in purine synthesis (glutamine PRPP aminotransferase) is inhibited by AMP, GMP, and IMP From IMP ATP and GTP stimulate production of the other monophosphate

Answer 17

AMP- 1. Amino removed to form IMP then hydrolyzed to inosine 2. AMP hydrolyzed to adenosine then deaminated to inosine Inosine converted to hypoxanthine by removing ribose, oxidized by xanthine oxidase to xanthine, xanthine oxidized to uric acid while involving hydrogen peroxide Uric acid is insoluble and causes gout GMP- Hydrolyzed to guanosine then form guanine from hydrolysis, deaminated to xanthine

Answer 18

Convert base to nucleoside monophosphate, important for cells that can't do de novo synthesis Take base and use phosphoribosyltransferase to add PRPP, one for adenosine and another for hypoxanthine/guanine to share

Answer 19

Caused by Adenosine Deaminase deficiency, which converts adenosine to inosine Get high levels of dATP which inhibits ribonucleotide reductase to prevent formation of dNDP (and later dNTP) from NDP Need dNTP for DNA synthesis like in actively proliferating cells like T and B lymphocytes Defective T and B cells lead to severe combined immunodeficiency

Answer 20

Xanthine oxidase converts hypoxanthine to xanthine to uric acid Formation of uric acid crystals in extremities instead of urine Caused by partial HGPRT deficiency or overreactive PRPP synthetase Allopurinol structurally similar to hypoxanthine and is a suicide inhibitor of xanthine oxidase

Answer 21

Defect in production or activity of HGTPT to cause increased hypoxanthine and guanine, results in increased uric acid Also increased PRPP stimulates production of purines to create vicious cycle Gout-like symptoms but also neurological abnormalities like aggression and self-mutilation

Answer 22

Start with simple materials then add PRPP 1. Form Carbamoyl Phosphate: ATP, Gln, and CO2 form Carbamoyl Phosphate via Carbamoyl phosphate synthetase II (committed step, similar to first enzyme but in cytosol not mitochondria) 2-3. Form Dihydroorate: carbamoyl phosphate condenses with Asp to form carbamoyl aspartate, then lose water to get dihydroorate 4-6. Form UTP: dihydroorate oxidized to orotic acid, combined with PRPP to form oritidine monophosphate, decarboxylated to UMP Use UMP kinase and then nucleoside disphosphate kinase to get UTP 7. Form CTP: UTP combined with Gln and ATP to form CTP, can't form other cytosine phosphate from other uridine phosphates directly

Answer 23

Occurs in liver, open rings to form soluble end products Cytidine forms beta-alanine Thymine forms beta-aminoisobutyrate, NH3, and CO2

Answer 24

Can't do efficiently so use kinases Uridine-cytidine kinase forms UMP or CMP and ADP from nucleoside and ATP Deoxycytidine kinase Thymidine kinase

Answer 25

Need to make NDP first, Ribonucleotide Reductase catalyze conversion to dNDP with help of NADPH RNR works for ADP, CDP, GDP, and UDP dUTP goes to dUMP then dTMP and eventually to dTTP

Answer 26

dUMP converted to dTMP by thymidylate synthase Methyl group donated by methylene THF, becomes dihydrofolate (DHF) Need to regenerate THF from DHF via dihydrofolate reductase (DHFR), ideal target for chemotherapeutic agents

Answer 27

Hydroxyurea: Targets ribonucleotide reductase Methotrexate: Targets dihydrofolate reductase Fluourouracil: Targets thymidylate synthase

9/6/17 Flashcards

(51 cards)