ERNSEM4B 2015-høst. Friday, December 18 09:00 to 12:00

Size: px

Start display at page:

Download "ERNSEM4B 2015-høst. Friday, December 18 09:00 to 12:00"

Marvin Parsons
5 years ago
Views:

1 ERNSEM4B 2015-høst Friday, December 18 09:00 to 12:00 The exam is in the form of multiple statements, some of which are correct. Read the statements very carefully and then indicate which you think are correct by marking the corresponding boxes. Note: There may be more than one correct statement in each section. If the box for a correct statement is ticked, you will get a mark. If the box for an incorrect statement is not ticked, you will get a mark. (Marks will not be deducted for wrong responses.) If you make a mistake, or change your mind, write a clear note beside the box that the mark should be ignored. You must return the question sheet marked with your candidate number. 1

2 IRON Iron absorption from the gut is enhanced by: Low iron stores Increased requirements Vitamin D supplements Calcium supplements Vegetarian diet Iron absorption is down-regulated by: Hepcidin Hefestin Transferrin Myoglobin Iron is actively excreted from the body by: The kidneys The gut The lungs There is no active excretion of iron Iron deficiency anemia in women is often associated with: Low energy intake Increased zinc intake Increased copper intake Low bioavailability of iron from the diet Increased requirements due to physical activity Select three possible sources of iron in a vegetarian diet: Milk Whole grain Eggs Nuts Legumes (peas, beans etc.) Tomato 2

3 What dietary advice would you give to a typical Norwegian man with primary haemochromatosis? Decrease consumption of fish Increase consumption of fruit Decrease consumption of red meat Increase consumption of bread Increase use of dietary supplements What are the two most common symptoms of iron deficiency in adults? Tiredness Vomiting Anorexia Reduced capacity for work Paleness Which of these statements is/are correct? Haemoglobin level is a good indicator of iron deficiency Transferrin-receptor is up-regulated in iron deficiency 70 % of iron in the body is bound to transferrin Hemosiderin is the main storage form of iron in the liver Ferritin is the major transport molecule for iron 3

4 MINERALS AND TRACE ELEMENTS Iodine: Fruits and vegetables are a good source of iodine In Norway, dairy products are a good source of iodine, as feedstuffs for cattle are supplemented with iodine Over a quarter of the world s population are estimated to be at risk of iodine deficiency Cretinism is a consequence of goitre in adults Signs of iodine deficiency show within hours of a reduction in iodine intake, as there is no store of iodine in the body 25% of the population in Norway takes in less than the recommended level of iodine and is therefore likely to suffer from goitre Iodine deficiency during pregnancy and early infancy leads to irreversible changes in the brain Zinc: Zinc in the body is mostly intracellular, with very little present in the blood Zinc fingers are involved in the transport of other metals, especially copper Zinc is a co-factor for more than 200 enzymes Zinc fingers bind to DNA and regulate gene expression There is no zinc reserve store in the body Zinc is stored in the liver Zinc fingers intercalate between the base-pairs of the DNA molecule Selenium: Selenium is involved in thyroid hormone production Selenium deficiency is linked to depletion of selenium in the soil In genes for selenoproteins the termination codon UGA codes for a specific trna charged with serine which is subsequently replaced with selenocysteine Selenium is a component of the antioxidant molecule glutathione Selenium is a component of the antioxidant enzyme glutathione peroxidase In Norway, dairy products are a good source of selenium, as feedstuffs for cattle are supplemented with selenium 4

5 Magnesium: Vegetables are a good source of magnesium Magnesium is an essential trace element, with about 25 g in the human body Magnesium associates with nucleotides in many enzymic reactions Magnesium Is mostly present in the blood Magnesium has a structural role in the nucleus, stabilising the DNA double helix. Magnesium is absorbed mainly in the small intestine Experimentally induced magnesium deficiency can lead to personality changes Copper: Shellfish are a good source of copper Green leafy vegetables are a good source of copper Copper is absorbed through the intestinal mucosa by binding to ceruloplasmin. Copper is important as a co-factor for one family of superoxide dismutases A high level of zinc in the diet can inhibit absorption of copper Keshan disease is a cardiomyopathy caused by copper deficiency Ultra-trace elements: Boron is an essential element in bones Manganese superoxide dismutase is the main antioxidant enzyme in mitochondria Silicon is involved in cartilage calcification Fluorine protects teeth against demineralisation, but it is probably not an essential element Arsenic is less toxic than selenium General: Phytate is a hexose sugar, found in whole grain bread, that binds minerals and promotes their uptake in the gut Metallothioneins are rich in SH groups that bind metals such as Zn, Cu and Cd Many enzymes involved in protection against oxidative stress are dependent on trace elements 5

6 VITAMIN A Which statement(s) about the vision cycle are correct? The pigment epithelium of the retina isomerises all-trans-retinol to 11-cic-retinol 11-cis-retinol may be reduced to 11-cis-retinal and transported to the photoreceptor cells Absorption of light by rhodopsin results in configuration change of 9-cis-retinoic acid Absorption of light by rhodopsin results in oxidation of opsin Opsin binds to transducin, which leads to activation of phosphodiesterase Symptoms of vitamin A deficiency include: Birth defects Anemia Night blindness Rickets Scurvy Bitot`s spot Nuclear receptor activation: In the absence of ligand, the nuclear receptors are bound to corepressor complexes that inhibit transcription The ligand binding leads to a conformational change of the receptors Conformational change of the receptors leads to oxidation of corepressors from the receptors. The ligand binding also leads to recruitment of coactivator complexes and other protein complexes that are required for transcription of the target gene Vitamin A deficiency in developed countries may be due to: Obesity Diabetes type 2 Hip fracture Malabsorption (e.g. Crohn's disease, cystic fibrosis) Eating disorders Secondary haemochromatosis 6

7 Which retinoids can bind to receptors in the cell? All-trans retinoic acid Retinol palmitate 9-cis retinoic aci 9-cis retinal All-trans retinol Which condition(s) would require vitamin A supplements? Pregnancy Lactation Excercise (above 1 hour per day) Coronary heart disease Xerophthalmia Vitamin A deficiency worldwide may be: due to low intake of animal products secondary to vitamin C deficiency linked to high frequency of infections secondary to iodine deficiency due to excess milk consumption General: Retinol is transported in plasma by binding to retinoid X Receptor (RXR) Beta-carotene has the same retinol activity as retinyl esters All carotenoids have retinol activity A concentration of retinol in the blood of 0,35-0,7 µmol/l is indicative of mild/moderate vitamin a deficiency 7

8 CALCIUM, VITAMIN D AND VITAMIN K General: Malnutrition and weight loss are associated with increased risk of osteoporotic fracture Intake of calcium and vitamin-d is more crucial for people around the age where peak bone mass is attained, in comparison to the need of children and elderly people. Intake of calcium and vitamin-d may together increase bone loss in postmenopausal women Meta-analyses show that vitamin D supplementation alone (without calcium) may have a marked effect on bone health if the serum level of 25-OH-D exceeds 125 nmol/l. What is the most likely diagnosis of a 13 year old girl with: 25 (OH) D3: 12 nmol/l, PTH 450 pg/ml, calcium 1,9 mmol/l? Osteomalacia Osteopenia Rickets Calcium: About 40 % of calcium from the diet is absorbed from the intestine Absorption of calcium occurs only by an active transport mechanism The recommended daily calcium intake in Norway for women and men is 800 mg Calcitonin is an important calcium-regulating hormone in humans Calcium is found in the blood in the form of Ca ++ or bound to albumin What are the short-term consequences of calcium deficiency? Hypocalcaemia Hyperkalaemia Calcification of soft tissues Decreased bone mass and increased risk of fractures What are the possible long-term consequences of excessive calcium intake from supplements? Hypocalcaemia Hyperkalaemia Increased risk of myocardial infarction Decreased bone mass and increased risk 8

9 Vitamin K: Menaquinone is the main synthetic form of vitamin K Vitamin K may activate the transcription factor RXR Vitamin K is absorbed from the small intestine and distributed to various tissues associated with chylomicrons. The absorption of vitamin K is independent of the amount of fat in the diet. The ratio of carboxylated osteocalcin/osteoblasts in the blood is considered the best parameter reflecting the patient s vitamin K status. Carboxylation of osteocalcin is associated with increased bone mass The best sources of vitamin K in an average Norwegian diet are: Fish and seafood Oils and green vegetables Fruits and berries Natto (fermented soy beans) Vitamin D: Vitamin D receptor (VDR) is a nuclear receptor After activation of VDR, biological effects can be observed after 2 minutes Activated VDR directly contacts RNA polymerase II VDR can both downregulate and upregulate transcription of its target genes VDR requires the same dimer partner as the vitamin A receptor Expression of the 1alpha-hydroxylase gene is repressed by VDR The most important dietary sources of vitamin D in an average Norwegian diet are: Bread and grain Fish and seafood Poultry and eggs Butter and margarine 9

10 VITAMIN E, OXIDATIVE STRESS AND ANTIOXIDANTS Reactive oxygen: 'Oxidative stress' occurs when the body's antioxidant defences are unable to cope with the effects of reactive oxygen Hydroxyl radicals are released from mitochondria during normal respiration Superoxide dismutase converts superoxide to hydrogen peroxide The Fenton reaction involves the oxidation and inactivation of a suicide enzyme The Fenton reaction depends on transition metal ions and produces hydroxyl radicals The Fenton reaction results in the inactivation of a reactive free radical The Fenton reaction is catalysed by a selenoprotein Superoxide is a reactive form of oxygen with an unpaired electron and so is referred to as a free radical Many transcription factors contain cysteine residues that are sensitive to modification by reactive oxygen species Oxidation of double bonds in proteins leads to the release of malondialdehyde, which can damage DNA Products of oxidation: Malondialdehyde is measured in the urine as a marker of DNA oxidation Oxidised lipids are taken up by lymphocytes and deposited in arterial plaques Lipid peroxidation is delayed (in an in vitro system) by the presence of antioxidants Carbonyl groups (>C=O) in proteins are a marker of oxidation Disulphide groups (-SS-) are a marker of protein oxidation Isoprostanes are a marker of protein oxidation Intrinsic antioxidants: Catalase removes peroxides by combining them with glutathione Glutathione is involved in many phase II biotransformation reactions Superoxide dismutase has a haem group at its active site A reduced superoxide dismutase activity is a symptom of anaemia. Glutathione (GSH), after oxidation to GSSG, is excreted from the body Catalase contains haem (iron) at its active site The oxidation of GSH to GSSG requires NADPH Regeneration of GSH from GSSG requires NADPH Glutathione is present at millimolar concentrations in the cell 10

11 Vitamin E: Vitamin E is bound to lipoproteins in the circulation Vitamin E can be regenerated by vitamin C The vitamin E molecule has a phytal chain γ-tocopherol is preferentially retained in the body Tocopherol transport protein is present in the plasma Vitamin E has 8 isomers Vitamin E, like vitamin A, is stored in the liver Vitamin E acts as an antioxidant by: acting as a free radical scavenger stimulating the formation of NADPH by the pentose phosphate pathway reducing oxidised glutathione to GSH Vitamin E deficiency can be due to: impaired lipoprotein synthesis fat malabsorption Vitamin E is present at high concentration in: almonds brown rice whole milk 11

12 WATER-SOLUBLE VITAMINS Homocysteine metabolism depends on four B-vitamins Mildly elevated homocysteine levels have been shown to cause myocardial infarctions Folate deficiency is more important than vitamin B12 deficiency for neurological disease Homocystinuria is usually due to cystathionine betasynthase deficiency Formation of urea is connected to formation of homocysteine via the so-called transmethylation reactions Vitamin B12 deficiency may lead to folate deficiency Homocysteine is neurotoxic Dementia is a rare disease B vitamins are standard treatments for dementia Plasma total homocysteine levels are often raised in dementia Low serum folate levels within the normal range are often found in Alzheimer's disease Raised homocysteine levels in Parkinson's disease are usually due to drug treatment Dementia is largely a genetic disease Beer contains significant amounts of vitamins Which of these accumulate(s) in people with low vitamin B12 (cobalamin) status? Succinic acid Homocysteine Methionine A patient with a history of alcoholism presents with several neurological signs, such as confusion, ataxia and disorientation in time or place. The cause is probably a deficiency in which vitamin(s)? Folate Thiamine (B1) Biotin Which of the following foods did early explorers find to be effective in preventing scurvy? Tinned meat (cooked) White wine Vinegar Cloudberries (multer) Fatty fish (cooked) Pine or spruce needles 12

13 Folate may play a role in the control of gene expression; by which mechanism(s)? Supply of energy in the cell nucleus Methylation of cytosine in DNA and of histones Regulation of mrna transcription Directly enhancing or changing protein function Demethylation of DNA and of histones Which vitamin deficiency linked to consumption of maize (corn) was associated with about 100,000 deaths in the USA in the first part of the 20 th century? Niacin Pantothenate Riboflavin (B2) What possible side-effect(s) is/are of concern in populations where mandatory folic acid fortification has been introduced? Increase in stroke Increased cancer Increased incidence of twins The status of water-soluble vitamins is often particularly inadequate in the elderly. Which? Folate Cobalamin Ascorbate Pantothenic acid 13

A deficiency of biotin, commonly seen in alcoholics, can cause neurological symptoms

Water-soluble vitamins Vitamin deficiencies Metabolism General Diseases etc. A deficiency of biotin, commonly seen in alcoholics, can cause neurological symptoms Levels of folate are particularly low in