Download ERN3120 Part 1 March 30 2012 09:00-13:00

ERN3120 Part 1
March 30 2012 09:00-13:00
All questions should be attempted.
Read each question carefully before starting to answer it.
You may write your answers in either English or Norwegian.
There are eight questions. Each consists of two parts. Section A requires a written answer: you should start
each answer on a new page. Section B is in the form of multiple choice questions: you should indicate
which you think are correct statements by marking the box. If you make a mistake, or change your mind,
write a clear note beside the box that the mark should be ignored.
In terms of grading, all questions have the same value, and within each question parts A and B are of equal
value.
Because parts B require marking on the question sheet, you must return the question sheet marked with
your candidate number, together with the written answers.
1
1. Vitamin A
A. Vitamin A-driven transcription regulation is important for embryonal development, growth, reproduction,
differentiation of epithelial tissues and immune response.
(i) Explain briefly how vitamin A is absorbed and stored
(ii) Describe how vitamin A influences gene transcription
B.
(i) Vitamin A has a well-documented effect in the treatment of:
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Dementia
Acute Promeolocytic Anemia
Microcytic Anemia
Acute Promeolocytic Leukemia
Anaphylaxis
Reducing the risk of mother-to-child HIV transmission*
*Needs more documentation [Note for sensor – not for students]
(ii) Vitamin A deficiency may be caused by:
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Low intake of animal products
Secondary to vitamin C deficiency
High infection frequency
Nitrous oxide abuse
Diabetes
Excess alcohol consumption
Fat malabsorbing conditions (such as pancreatitis, cystic fibrosis, tropical sprue & biliary obstruction)
(iii) Vitamin A is a generic term for a number of related compounds. Which of the following are vitamin A?
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Retinal
Xantophylls
Lutein
Lycopene
Gamma-carotene
(iv) Vitamin A is important for:
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Colour vision
Reducing the risk of pancreatic cancer
Gene transcription
The function of red blood cells
Muscle tone
Dermatology
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2. Genetic polymorphisms
A. What is an SNP? In what ways can SNPs affect biochemical/physiological effects in the body? Why are SNPs in the
human genome being studied so enthusiastically?
B.
(i) A common complex disease affects at least 1 in 1000 people [In error this was printed as 1 in 10.000 in the exam
paper – but corrected in the course of the exam]. For which of the following is this true?
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Type 2 diabetes
Multiple sclerosis
Breast cancer
Colon cancer
Cystic fibrosis.
(ii) A genetic component in a disease is suspected if
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there is a higher frequency of the disease in first degree relatives of the patient
there are differences in incidence of the disease between different countries
the incidence of a disease in an ethnic group changes when members of the group migrate to another country.
(iii) Twin studies have shown that coronary heart disease and diabetes show a higher concordance rate in monozygous
twins than in dizygous twins. This indicates that
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genetic factors are more important
environmental factors are more important
coronary heart disease and diabetes are genetically linked.
(iv) Children of obese parents are 10 times more likely to be obese than children of parents of normal weight. This
indicates that
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genetic factors are most important in causing obesity
obese children grow into obese adults.
(v) The ‘thrifty gene hypothesis’ proposes that:
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Genes that encourage storage of fat in the body had a selective advantage in (pre)historic times when famine
was common.
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Obesity is increasingly common because of an increased occurrence of ‘thrifty gene’ mutations in human
populations.
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‘Thrifty genes’ can predispose humans to metabolic syndrome and type 2 diabetes.
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3. Micronutrients
A. Both in the media and in the scientific literature, antioxidants are said to:
• Protect against chronic diseases such as cancers and cardiovascular diseases
• Be harmful and increase risk of disease
• Have no effect on disease initiation or development
Discuss these statements on the basis of the current scientific evidence. To what extent are the statements actually
contradictory?
B.
(i) Which of these groups of chemicals include only examples of polyphenols?
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Flavonoids, stilbenes, and lignans
Carotenoids, flavones, and anthocyanins
Phytoestrogens, folate, and ubiquinone
Quercetin, glutathione, and tannins
(ii) In which of the listed foods will you normally find high levels of flavonoids?
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Milk
Tea
Blackberries
Chicken
Onion
Red meat
(iii) Which of the following statements are true?
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All polyphenols are antioxidants in vivo
All carotenoids have “provitamin A” activity
Flavonoids may induce the expression of phase I and II enzymes
Flavonoids are important for normal vision
(iv) Which of the following are proposed as mechanisms to explain how phytochemicals (plant chemicals) may exert
protective effects towards CVD or cancer?
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Increase DNA repair
Decrease the expression of phase II enzymes
Decrease inflammation and production of inflammatory mediators
Decrease platelet aggregation
Increase eNOS activity
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4. Cancer and nutrition
A. What is the biological significance of oxidative damage to DNA? How is it commonly measured? How can the
measurement of DNA oxidation help us to understand the role of dietary antioxidants?
B.
(i) Chromosome damage:
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The level of chromosome aberrations in an individual’s white blood cells is a significant predictor of future
cancer risk.
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Chromosome aberrations are simply rearrangements of genetic material which do not kill the cell, whereas
micronuclei involve loss of DNA from the nucleus and are therefore lethal.
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Micronuclei appear only in non-dividing cells.
(ii) DNA repair
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Bulky adducts induced by many food mutagens are recognised and repaired by nucleotide excision repair.
The first step in base excision repair is removal of the altered base by an endonuclease.
Base excision repair tends to introduce mutations as it is inaccurate.
(iii) P53 is an important checkpoint protein, sensitive to DNA damage and determining whether a cell will go into
apoptosis or take a break from the cell cycle to repair the DNA damage.
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The P53 gene is a protooncogene.
P53 mutations are common in many cancers. Mutations in P53 are recessive.
P53 mutations typically appear late in the sequence of genetic changes associated with colorectal cancer.
(iv) Cytochrome P450 (CYP450) enzymes are involved in
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DNA repair
biotransformation
detoxifying xenobiotics.
CYP450 enzymes tend to be induced by their substrate.
CYP450 enzymes render potential carcinogens such as benzo(a)pyrene less reactive.
(v) Among the various causes of cancer,
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Diet is less important than environmental pollution
Diet and smoking are equally important
The influence of diet on cancer incidence is largely attributable to artificial food additives
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5. Vitamin E, oxidative stress and antioxidants
A. Give an account of the bioavailability and biological effects of vitamin E, including mechanisms of regulation of
vitamin E status.
B.
(i) In the Fenton reaction,
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Iron (Fe) is oxidised and excreted from the body
Highly reactive superoxide is converted to H 2 O
Superoxide (O 2 ●-) is converted, via H 2 O 2 , to the highly reactive hydroxyl radical (●OH)
Vitamin E acts as a catalyst in the reduction of reactive oxygen species
(ii) Free radicals
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All free radicals are reactive oxygen species
All reactive oxygen species are free radicals
(iii) There is a strong negative association between plasma levels of α-tocopherol and coronary heart disease.
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This implies that low α-tocopherol causes heart disease
This implies that high α-tocopherol prevents heart disease
(iii) Vitamin E is normally obtained in sufficient quantity from the diet. Good sources are
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Fish
Plant oils
Nuts
Flour
However, a vitamin E deficiency can occur in
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individuals with a defect in fat metabolism
pregnant women
very low birth weight infants
(iv) Glutathione is
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a suicide enzyme involved in DNA repair
commonly conjugated to toxic chemicals
rich in selenium
part of the body’s antioxidant defences
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6. Vitamin D and vitamin K - bone health
A. Vitamin K belongs to the quinone class of molecules. Which of the K-vitamins are important for the human
organism? What are their main sources (nutritional and other)? Describe briefly the absorption, transport and storage of
vitamin-K. Describe briefly the mechanism of action of vitamin-K and its impact on the effect of osteocalcin in bone.
How is an individual’s vitamin-K status measured?
B.
(i) Metabolism of vitamin-D:
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Parathyroid hormone or high serum Ca2+ levels stimulate kidney 1α-hydroxylase, resulting in the production of
calcitriol, the active vitamin-D analogue.
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Certain drugs such as anticonvulsants may interfere with the liver hydroxylation of vitamin-D and reduce the
circulating levels of calcidiol.
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UVB rays stimulate the production of Vitamin-D from pre-vitamin-D in the skin, as well as the destruction of
excess Vitamin-D produced.
(ii) Bone turnover:
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The osteoclast is differentiated from stem cells under the influence of factors such as calcitriol, PTH
(parathyroid hormone), glucocorticoids and interleukins.
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The osteoblast produces RANK-L (RANK-ligand), which in turn activates the osteoclast to resorb bone.
RANK-L is blocked by the decoy receptor OPG (osteoprotegerin), also produced by osteoblasts.
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Post-menopausal bone loss, due to oestrogen deficiency, can be explained by an enhanced RANK-L/OPGratio, enhanced T-cell activity, reduced osteoblast ability to produce and mineralize bone matrix, and a reduction in the
reabsorption of Ca2+ in the kidney.
(iii) Osteoporosis, aetiology:
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Risk factors that, in principle, cannot be influenced are: sex, age, previous fractures, early menopause, heredity,
ethnicity, body height, body weight, chronic gastrointestinal (GI) diseases.
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Risk factors that, in principle, can be influenced are: Low BMD, physical activity, weight loss, rapid changes
in body weight, corticosteroid treatment, muscle strength, smoking, urine incontinence, sun exposure, and low peak
bone mass.
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Ca2+ and Vitamin-D supplements may prevent fractures in elderly people; the combination may reduce bone
loss in patients using corticosteroids; Ca2+ and Vitamin-D given separately (either one or the other) do not influence
bone mass in a positive manner.
(iv) Monogenic bone disease:
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VDR (vitamin D receptor) polymorphism may cause osteomalacia.
CYP19 (liver hydroxylase) polymorphisms may cause osteomalacia.
OPG polymorphisms may cause reduced osteoclast activity.
ER (oestrogen receptor) polymorphisms may cause enhanced bone resorption.
Collagen1α1 polymorphism may cause osteopetrosis (enhanced bone mass).
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7. Food toxicology
A. Select one of the following classes of food toxin: Nanoparticles, or Mycotoxins, or Heavy metals. Explain (with one
or two examples) how they get into our food or drink, and why they are considered to be hazardous. Do you think they
represent a real health risk in Norway?
B.
(i) The ‘margin of safety’ is used to set maximum acceptable daily intake (ADI) for food additives, etc. By convention,
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The ADI is expressed as mg/kg/day
The ADI is expressed as mg/day for an average adult
The ADI is 1000 times lower than the mean lethal dose (LD50) established in animal experiments
The ADI is 100 times lower than the ‘No observed adverse effect level (NOAEL) established in animal
experiments
(ii) Toxicity depends on how a toxin enters the body. Which route is generally more toxic?
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Intravenous
Oral
(iii) An ‘antagonistic effect’ describes
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a combined toxic effect of two chemicals that is greater than either of them alone
a combined toxic effect of two chemicals that is more than additive
a combined toxic effect of two chemicals that is less than additive
(iv) In toxicity testing, it is advisable to carry out a dose response experiment – exposing the animals or cells to a range
of concentrations of the supposed toxin. This is done in order
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to establish the LOAEL
to establish causality between exposure and effect
to establish LD50
to determine the ratio of LD50 to LOAEL
to determine how sharply the adverse effect increases (from the slope of the curve)
(v) Which of the following toxins can be classified as ‘natural toxins’?
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Vicin (in broad beans)
Acrylamide
Amanitin
Lactose
Solanine (in green potatoes)
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8. Minerals and trace elements
A. What methods have been used to gain information about the absorption of iron in humans? Give an overview of the
results that have been obtained.
B.
(i) Which of the following are trace elements (recommended daily intake < 100 mg/day)?
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Magnesium (Mg)
Iron (Fe)
Phosphorus (P)
Iodine (I)
Zinc (Zn)
(ii) Good sources of zinc:
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Eggs
Red meat
Fish
Nuts
Green vegetables
(iii) Selenium (Se) substitutes for sulphur (S) in selenoproteins.
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There is a specific tRNA that binds selenocysteine
tRNA carrying cysteine is modified by substituting S with Se
Serine bound to tRNA is modified by addition of Se
Selenium deficiency is increasing in European populations because
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Less fish is eaten than in the past
Home produced wheat has lower levels of Se than imported wheat
Less whole grain food is eaten than in the past
(iv) Magnesium
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Mg is an essential component of many structural proteins
Mg stabilises the DNA double helix
Mg-ATP is the energy provider for many cellular processes
Most Mg in the body is found in the muscles
Chlorophyll contains Mg and so green vegetables are a good source of Mg
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Sensorveiledning for parts A of questions
1. Vitamin A
a)
Retinyl esters (RE) are converted to retinol in the lumen by a combination of bile and pancreas esters, taken
up by the epithelial cells where they are re-esterified and wrapped in chylomicrons. Approximately 80% of
retinyl esters are absorbed as retinol in healthy subjects eating a “normal” diet.
Beta-carotene is taken up by the epithelial cells by passive diffusion, converted to two retinal molecules,
which are then converted to retinol and esterified by the enzymes ARAT or LRAT. Only 5-50% of
carotenoids are absorbed in the lumen (depening on which carotenoid, amount, isomere, food preperation,
fat present in the diet etc). Poor absorbtion in raw or quickly stir fried vegetables, best with a little bit of
fat, presence of bile acids critical. Amount absorbed is decreased with increased amounts eaten.
Within the intestinal epitelia, the retinol is bound to cellular retinol binding protein type II (CRBP II) and
incorporated into chylomicrones. The chylomicrones are transported by the lymph system into the blood
straem and fatty acids/other compounds are transported to various tissues.
Chylomicron-remnants is mainly taken up by the liver, some in other tissues. Approximately 80-90% of
vitamin A found in liver of healthy subjects. Vitamin A is stored well. Hepatocytes make up the majority of
liver cells, containing small amounts of retinol and retinyl esters. These cells take up chylomicron-remnant
particles and synthesize and release the plasma RBP. RE is hydrolysed into retinol (ROH) in hepatocytes.
ROH is bound to RBP in the ER and released from the hepatocytes to the bloodstream or stellat cells.
Stellat cells constitute about 5-15% of liver cells. In these cells, retinol is estereified to its storage form, RE.
Stellat cells are the main storage of vitamin A. Some vit A can be stored in other tissues such as adipose
tissue, lung, testes, bone marrow, eyes and kidneys.
b)
Vitamin A enters the cells through chylomicrones (chylomicrone receptor) or through vitamin A bound to
retinol binding protein (RBP Receptor). Inside the cell, the conversion of retinaldehyde to retinoic acid is
irreversible, meaning that this step is tightly regulated. Retinoic acid can be produced in the body by two
sequential oxidation steps that convert retinol to retinaldehyde to retinoic acid, but once produced it
cannot be reduced again to retinol. The enzymes that generate retinoic acid for control of gene expression
include retinol dehydrogenases (i.e. Rdh10) that metabolize retinol to retinaldehyde, and retinaldehyde
dehydrogenases (Raldh1, Raldh2, and Raldh3) that metabolize retinaldehyde to retinoic acid. Enzymes that
metabolize excess retinol to prevent toxicity include alcohol dehydrogenase and cytochrome P450(cyp26).
Retinoic acid regulate transcription by binding and activating the ligand-dependent transcription factors
known as retinoic acid receptors (RARs), which form heterodimers with retinoid X receptors (RXRs). RARs
and RXRs are members of the nuclear receptor superfamily of transcription factors. There are six different
retinoic acid receptors . RAR is activated by its ligand all-trans retinoic acid (at-RA), whereas RXR is
activated by 9-cis retinoic acid (9c-RA). It is not known whether 9-cis-retinoic acid is found in vivo; if so, it is
only present in very small amounts.
The RAR/RXR heterodimer binds to a specific sequence of bases in DNA, called a DNA element, or retinoic
acid responsive element (RARE). The consensus sequence for the half binding site is AGGTCA. Once the
heterodimer is activated, it can induce the expression of target genes, by binding to the promoter of these
genes. Many of the vitamin A target genes are involved in vitamin A metabolism, e.g. the enzyme LRAT.
Other target genes are transcription factors involved in development and differentiation.
2. Genetic polymorphisms
Single Nucleotide Polymorphisms (SNPs) occur approximately once every 300 to 1000 bases. They are single
pase pair sites in the genome where (usually two) different basepairs can commonly be found among
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individuals of natural populations. SNPs in the gene(s) involved in complex disease susceptibility can affect
gene expression in several ways:
• Certain SNPs in the coding sequence of a gene can alter biochemical activities of enzymes, proteins,
and cellular processes.
• SNPs in 5' or 3' regulatory regions (e.g. promoters) are likely to play a role in regulating gene
expression.
• SNPs may also alter splicing. Over 30,000 alternative splice sites have been identified in a genomewide analysis of humans.
There is great interest in SNP discovery because of their potential to facilitate large-scale gene mapping and
genetic association studies. By indentifying and mapping SNPs to the human genome sequence a map is
being created of human genetic differences. These SNPs usually do not cause a disease by themselves, but
they can be used to find disease-causing and susceptibility genes.
3. Micronutrients
Students in Oslo: In the discussion the students should mention;
• different methodologies might give very different results (cell culture, animal experiments, clinical
trials, epidemiological studies, etc)
• diverse interventions or dietary exposures (one or several antioxidants in supplements, one or
several antioxidant-rich fruits/berries/vegetables/nuts). Conclusions are often drawn for
“antioxidants” when in fact the trail included only single supplements (e.g. vitamin E or 
-carotene)
or one plant food (e.g. bilberries), and should conclude accordingly.
• the doses of exposure
• the obstacles to performing clinical trials with dietary interventions to test the “antioxidant
hypothesis” (rather than supplements)
• the role of the investigator (his or her prior perception of the research field)
When addressing the final question (To what extent are the statements actually contradictory?), the
students should discuss that all three statements may be true, mostly depending on the doses and the
clinical setting. The points for discussion above are also vital to this question, and one integrated
answer for the whole assay question should be accepted.
High doses of selected antioxidants seem to increase the risk of disease (e.g. 
-carotene and lung
cancer in smokers or total mortality). Also, antioxidants may not yield statistically significant effects all
trials and studies, either because such an effect does not exist for the selected antioxidant(s) or doses,
or because the study is not designed to detect the actual effect.
Diets rich in plant based foods (and thus rich in compounds with antioxidant properties) have
preventive effects towards several chronic diseases. Whether the prevention is due to direct
antioxidant properties or other properties of bioactive compounds in plant foods is still unclear.
Unfortunately, conclusions are quite often drawn for the effects of fruits and vegetables based on
studies with supplements, or vice versa.
Students in South Africa:
In the discussion the students should mention;
• different methodologies might give very different results (cell culture, animal experiments, clinical
trials, epidemiological studies, etc)
• different interventions or dietary exposures (one or several antioxidants in supplements, one or
several antioxidant-rich fruits/berries/vegetables/nuts).
• the doses of exposure
When addressing the final question (To what extent are the statements actually contradictory?), the
students should discuss that all three statements may be true, mostly depending on the doses and the
clinical setting. For students in South Africa, the most weight should be put on the discussion and it
should be acceptable if they answer that these statements are contradictory, provided they still have
reasonable discussion including methodology, intervention and doses.
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The points for discussion above are also vital to this question, and one integrated answer as a whole for
the assay question should be accepted.
High doses of selected antioxidants seem to increase the risk of disease (e.g. 
-carotene and lung
cancer in smokers or total mortality). Also, antioxidants may not yield statistically significant effects all
trials and studies, either because such an effect does not exist for the selected antioxidant(s) or doses,
or because the study is not designed to detect the actual effect.
Diets rich in plant based foods (and thus rich in compounds with antioxidant properties) have
preventive effects towards several chronic diseases. Whether the prevention is due to direct
antioxidant properties or other properties of bioactive compounds in plant foods is still unclear.
Unfortunately, conclusions are quite often drawn for the effects of fruits and vegetables based on
studies with supplements, or vice versa.
4. Cancer and nutrition
Oxidative damage to DNA can lead to mutations, and if these are in certain genes (such as oncogenes,
tumour suppressor genes or mutator genes) cell transformation can result, leading to cancer. DNA
oxidation results from free radical attack. Free radicals are produced within the cells (mitochondrial
leakage) and also occur in the environment (e.g. tobacco smoke). DNA oxidation is measured by
chromatography (HPLC, GCMS) or with the comet assay plus lesion-specific enzymes (FPG, endoIII). DNA
oxidation can serve as a biomarker of oxidative stress or antioxidant protection – usually measured in white
blood cells. For instance, the level of DNA oxidation can be measured in individuals and related to the blood
level of particular dietary antioxidants. Alternatively, subjects can be supplemented with antioxidants, and
effects detected by monitoring DNA oxidation in wbcs. Antioxidant status can be assessed by treating wbcs
in vitro with H 2 O 2 and measuring the breaks induced in DNA.
5. Vitamin E
1. The term vitamin E denotes a family of tocopherols and tocotrienols, plant lipids that are essential
for vertebrate fertility and health. There are eight naturally occurring homologues of vitamin E,
which differ in their structure and in biological activity in vivo and in vitro.
2. The principal form of vitamin E found in humans, RRR-alpha-tocopherol is mostly available in
tissues. Various studies have suggested that after normal gastrointestinal absorption of dietary
vitamin E specific mechanisms favour the preferential accumulation of one of its homologues, RRR
alpha-tocopherol, in the human body.
3. This process is mediated by the alpha-tocopherol transfer protein (TTP) in the liver cytoplasm. The
mechanism and pathway by which TTP specifically incorporates alpha-tocopherol into plasma
lipoproteins is not yet fully understood. Through the action of TTP, RRR-alpha-tocopherol is then
secreted from the liver into circulating lipoproteins that deliver the vitamin to target tissues.
Regulation of vitamin E homeostasis occurs in the liver, where RRR-alpha-tocopherol is selectively
retained while other forms of vitamin E are degraded
4. Recent data indicate that a system of alpha-tocopherol-binding protein (TBP/associated protein
(TAP) is involved in the processes that favour the localization of alpha-tocopherol at the
intracellular sites where it is required..
5. Genetic deficiency in TTP (Ataxia), TTP gene polymorphisms, and TTP gene knock out animal model
should also be discussed
6. Vitamin D and vitamin K
1) Which of the K-vitamins are important for the human organism? Phylloquinone (K1), Menaquinone
(K2).
2) What are their main sources (nutritional and other)? K1; from plants (green vegetables, fruit and plant
oils). K2; Produced by Gram-negative bacteria in the distal GI-tract.
3) Describe briefly the absorption, transport and storage of vitamin-K. Absorption; with dietary fat,
influenced by liver and pancreas, 40-70% absorbed via jejunum/ileum. Transport; within chylomicrons.
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Storage: Mainly in the liver, via Chylomicron remnant particles. Small amounts are stored in bone. Vit-K
reserves last for approx. one day.
4) Describe briefly the mechanism of action of vitamin-K
and its impact on the effect of osteocalcin in bone. Vit-K
acts as a “co-factor” in reactions yielding carboxylation on
Glu-residues of various proteins, e.g. osteocalcin. Vit-K
serves (in the form of Vit-K hydroquinone) as an H+
“scavenger” to enable insertion of CO 2 adjacent to the
carboxylic residue of Glu. Vit-K is subjected to a cyclic
reactivation pathway (see figure, right). Carboxylated
osteocalcin now has two -COO- groups on Glu-residues,
enabling the protein to chelate Ca2+, thus holding it in
position to form hydroxyapatite crystals to be deposited
onto the bone matrix proteins.
5) How is an individual’s vitamin-K status measured? VitK status is best measured as uncarboxylated (or
carboxylated), but not total, osteocalcin, since there is an
inverse relationship between circulating Vit-K and
uncarboxylated osteocalcin.
7. Food toxicology - choice of nanoparticles, mycotoxins, or heavy metals
Nanoparticles:
Define as particles with at least one dimension less than 100 nm.
Examples of NPs - iron oxide, silver, titanium dioxide, carbon.
Can get into food from packaging, from additives, from equipment used in food preparation/cooking.
Nanoparticles have very large surface area relative to their mass, which makes them more reactive than the
corresponding bulk material.
Because of their size, they can penetrate cells, and cross the blood-brain barrier.
NPs are increasingly common in our environment, and so exposure is inevitably increasing.
Risk in Norway? Unknown. More research is needed.
Heavy metals:
Examples: Mercury, lead, cadmium, chromium.
Enter food from industrial pollution of ground and water.
Once in the body, are not eliminated by cytochromes P450, and tend to accumulate, e.g. in fat. Significant
amounts of e.g. mercury in fish, especially species at the top of the food chain.
Toxicity: Interfere with enzyme action (e.g. Hg, As), neurotoxic (e.g. Pb), oxidative damage (e.g. Cr),
genotoxic (e.g. Pb, Cd, Cr).
In Norway, there is a testing programme, and accordingly recommendtions are made - e.g. to eat only a
certain number of meals of fish each week. So risk is minimal.
Mycotoxins:
Define as toxins produced by fungus.
Example: Aflatoxin, from Aspergillus.
Procarcinogen - activated by CYP450, especially in the liver, to reactive form which can form bulky adducts
on DNA. If not repaired, these can lead to mutations and so to transformation and cancer.
Aflatoxin is found in badly stored grain, nuts etc. (humid warm conditions).
Risk is high in poor, tropical countries and is increased in subjects with hepatitis.
Risk in Norway is low, as good controls exist - tests are carried out on susceptible imported foods.
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8. Minerals
KOSTJERN FOREKOMMER I 2 FORMER:
o ionisert el. ioniserbart jern, dvs, ikke-hemjern (i kjøtt, fisk,
fjærfe, egg, korn, grønnsaker og frukt)
o hemjern (i kjøtt, fisk, fjærfe; ca 40% av totaljernet)
ABSORPSJON AV KOSTJERN: METODER OG RESULTATER
De forskjellige stadier i utviklingen av kunnskap henger sammen med de metoder som har vært
tilgjengelige.
1. Balansemetoden, B = Inn - Ut.
Balanse = likevekt
Balansen er av svært liten størrelsesorden, 1-2 mg, derfor er det store feilkilder, dessuten vanskelig
å utføre. Fordelene var: blandete koster, forsøk over lang tid.
Resultater: Total absorpsjon av jern fra et måltid varierte fra 7-21% (i forsøk med flere
forsøkspersoner vil det være forskjeller i jernstatus).
2. Biologisk merking av næringsmidler med én radioaktiv isotop (inkorporering
med 59Fe).
Planter gjødslet med f eks 59Fe-EDTA kompleks; dyr fôret med jernmerket kost. Testing av
enkeltmatvarer.
Resultater: Variasjon mellom individer; størst opptak hos dem med jernmangel, mao, individets
jernstatus påvirker absorpsjonen. Absorpsjonen fra vegetabilier dårligere enn fra animalsk føde.
Absorpsjonen varierer dessuten for de enkelte vegetabilier og for de enkelte animalske matvarer.
3. Biologisk merking med to radioaktive isotoper, (inkorporering av 55Fe og
59
Fe).
F eks testing av 55Fe-merkete vegetabilier og av 59Fe-merket kjøtt.
Resultater: Vegetabilier og animalsk føde påvirker hverandre gjensidig.
4. "External" og "internal tag", (el. "extrinsic" og "intrinsic tag").
Absorpsjonen av én isotop (f eks 59Fe) tilsatt biologisk (=inkorporert isotop) til matvaren og
absorpsjonen av en annen isotop (f eks 55Fe) tilsatt til matvaren på tallerkenen måles.
Resultater: Isotopene absorberes likt, dvs, alt ikke-hemjernet blandes i én pool uansett om en
plante har inkorporert en "tag" ("internal") eller om man har tilsatt en "tag" (external") til
plantekosten. Det er fullstendig utbytning mellom disse. Dette gjelder for begge typer jern og er
vist for en lang rekke næringsmidler.
Hemjern og ikke-hemjern absorberes forskjellig; det er 2 pooler. (Vist ved å merke hemjern og ikkehemjern med hver sin isotop.)
Metoden med "external tag" har gitt muligheter til å studere absorpsjonen fra ulike sammensatte
måltider og dermed hvordan de enkelte næringsmidlene påvirker hverandre. Komplisert samspill;
de virker henholdsvis hemmende (garvesyre (=tannic acid), fytinsyre, oa) og stimulerende
(askorbinsyre, kjøttfaktor) på hverandre.
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