NMDF211 Nutritional Biochemistry · NMDF211 Nutritional Biochemistry Topic: ... Only free thiamin...

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NMDF211

Nutritional Biochemistry

Topic: Water Soluble Vitamin Pharmacokinetics

Nutrient control of gene expression

Session 2


Session Objectiveso Understand the biochemical processes underpinning the

digestion, absorption, transportation and metabolism of

water soluble vitamins.

o Nutrient control of gene expression


Vitamin C Absorption

Carrier Mediated

DiffusionDehydroascorbate

Ascorbate

Dehydroascorbate

It doesn’t need any digestion prior its absorption.

Absorption is regulated by concentration where high

dose down regulates transport.

Ascorbate

(Majority)

Vitamin C

Ascorbate

GLUT 1 and 3

transporters

Na+ Active

Transport

(Sodium

dependent

Vitamin C

Transporter)

Dehydroascorbate

Reductase

95%

Ascorbate

(Free Form)

5%

Dehydroascorbate

(Free Form)


Vitamin C Absorption

Glutathione is essential for Vitamin C metabolism

Ascorbic

Acid

Dehydroascorbic

Acid

GSSG

Oxidised

Glutathione

2GSH

Reduced

Glutathione

Semidehydroascorbic Acid Radical

Dehydroascorbate

Reductase


Vitamin Co Vitamin C absorption decreases with increased vitamin

intake

Absorption varies:

►High vitamin intake = 16% vitamin C absorption

►Low vitamin intake = 98% vitamin C absorption

o Note: Around 50% absorption of a 1000mg dosage

o Overall average intake is about 70-95%

o Unabsorbed vitamin C may be metabolised by intestinal

flora (large intestine).

o Large amounts of iron present with vitamin C in the

digestive tract results in an oxidative decrease of Vit C.


Vitamin Co The uptake of vitamin C into cells requires sodium and a

carrier and sometimes is energy dependent (such as

leukocytes).

o Found in all cells, especially:

Highest: Adrenal and pituitary glands

Intermediate: Liver, spleen, heart, kidneys, lungs,

pancreas and leukocytes

Small: Muscles and red blood cells

o Agonists – Glutathione

o Antagonists – pectin, zinc, copper, high dose of iron


Vitamin C

o Vitamin C is responsible for “Hydroxylase” enzyme

action i.e. Energy production, collagen production (+

proline, lysine, glycine and iron).

o Proline, lysine Ascorbate hydroxyproline, hydroxylysine

Hydroxylase

o These hydroxylated forms make up 2/3 of all collagen

fibre (Iron is also required in this reaction).


Revision Questions

o What substance is necessary to reform ascorbate from

dehydroascorbate and is essential for vitamin C

metabolism?

o Is the absorption of vitamin C influenced by intake

concentrations?

o Name 2 antagonists of vitamin C?

o Which cells have the highest concentration of vitamin C?

o Vitamin C is necessary to activate which enzyme

responsible for energy production and collagen

synthesis?


Thiamin – Vitamin B1Sources:

o Meat (esp. pork)

o Legumes

o Whole grains

o Breads

o Cereals

o Yeast

o Wheat germ

Forms:

1. Plant based form: nonphosphorylated free form

1. Animal based forms: (Phosphorylated form/complex forms)

a) Thiamin monophosphate (TMP)

b) Thiamin diphosphate (TDP) or Thiamin pyrophosphate (TPP) (same molecule different names)

c) Thiamin triphosphate (TTP)

Intestinal phosphatases must hydrolyse the phosphates prior to absorption


Thiamin FactorsAnti-Thiamin Factors/Antagonists:

1. Raw fish: ‘Thiaminases’ cleaves thiamin but cooking

fish destroys thiaminases.

2. Polyhydroxyphenols: Tea, coffee, betel nuts,

blueberries, Brussel sprouts, red cabbage by oxido-

reductive process.

Agonist:

o Reducing compounds such as vitamin C and citric acid

can prevent the destruction of thiamin.

• (Gropper & Smith, 2016)


Thiamin Absorption

B1 Thiamine Transporters

(ThTr1 and ThTr2)

B1 (>2.5mg) Passive Diffusion

B1 maybe

phosphorylated into

phosphate ester

Alcohol inhibits the intestinal

expression of ThTr1 and ThTr2 and

thus thiamine absorption.

Only free thiamin is absorbed into the small

intestinal cells;

Phosphatases in the small intestines are

required to break the phosphate bonds with

the thiamin to produce free thiamin (animal

based diets).

http://www.newdirections.on.ca/images/Gastrointestinal.gif



Thiamin Absorption

90% Thiamin found in blood cells

RBC: TDP

Facilitated diffusion

Other Tissues:

i) Thiamin (free form) (Albumin)

ii) Thiamin monophosphate (TMP)

Active transportActive transport

Liver – B1 converted to its coenzyme TDP (thiamin diphosphate)

Thiamin pyrophosphokinase

Thiamin TDP (80%)/TTP(10%)

ATP AMP

Skeletal muscles

Heart

Kidneys

Brain

Active

Transport

B1ThTr1

Most thiamine exists in body as TDP.


Revision Questions

o Name the two co-enzyme forms of thiamin?

o Name three foods which contain anti-thiamin factors?

o Name two substances which prevent the destruction of

vitamin B1?

o What are the group of enzymes which break the

phosphate bonds with thiamin prior to absorption?

o In high concentrations of B1 ingestion, by what

mechanism does transport over the brush border occur?

o By what mechanism does the uptake of B1 occur into

cells?


Riboflavin – Vitamin B2Sources:

Found in a wide variety of foods, especially those of animal origin.

o Milk and Milk products e.g. cheese, yoghurt

o Green Vegetables

o Eggs

o Meat

o Very small amounts in legumes and grains

Riboflavin Form: (may be destroyed with exposure to sunlight)

1. Free Riboflavin and Protein-bound riboflavin (in milk & eggs etc)

2. Coenzyme derivatives:

• FMN (Flavin mononucleotide)

• FAD (Flavin adenine dinucleotide)

3. Phosphorus bound riboflavin and amino acid bound FAD


Riboflavin Digestion

FAD

FAD pyrophosphatase

FMN

FMN phosphatase

Riboflavin

Riboflavin phosphate

nucleotide diphophosphatase OR

alkaline phosphatase

Riboflavin

FAD bound to cysteine or histidine

– not broken down and not utilised by

the body. Excreted unchanged

Gastric Intestinal Enzyme

B2 with nonconvalent bonds to protein

Hydrochloric acid

Riboflavin




Riboflavin AbsorptionRiboflavin Absorption

o Most B2 is absorbed in duodenum

o B2 is absorbed via

1. Active transport (Riboflavin Transporter 2 - RFT2)

2. Passive diffusion at high concentrations

3. Saturation dependent – amount 95% is absorbed (max 25mg)

Antagonists

1. Alcohol interferes with digestion and absorption.

2. Foods bound with Histidine and cysteine.

3. Exposure to sunlight.

4. Excretion of Riboflavin is enhanced with diabetes mellitus,

trauma and stress.

5. Thyroid disease alters the metabolism.


Riboflavin Absorption

Flavokinase

Riboflavin FMN

ATP ADP Riboflavin

(Albumin)

FAD synthetase

FAD FMN

ATP PPi

Transported via plasma proteins (Albumin,

fibrinogen, and globulins e.g.Immunoglobulins)

Active

Transport

Riboflavin

Active Transport

(RFT2)

**Immunoglobulins use riboflavin

to produce H2O2 to assist

destroying foreign antigens

Uptake into liver appears

to be regulated by calcium


Riboflavino FMN is the predominant flavoenzyme found in tissues.

o Metabolism is under hormonal control. ACTH,

aldosterone and thyroid hormones conversion of

riboflavin to its flavoenzymes: FMN FAD

o Severe deficiency in B2 can interfere with coenzyme

reactions involving energy production, Vitamin B6

metabolism, synthesis of niacin from tryptophan etc.

Highest Concentrations (stored):

o Liver, Kidney, Heart


Revision Questions

o What are the two co-enzyme forms of riboflavin?

o Name three antagonists of vitamin B2?

o Which protein carrier transports majority of B2 through

circulation?

o The highest concentrations of B2 exist in which organs?


Vitamin B3

(Niacin, Nicotinic Acid, Nicotinamide)

Sources:

Tuna Halibut

Beef Chicken

Turkey Pork

Enriched cereals Bread products

Whole grains Seeds

Legumes


Niacin, Nicotinic Acid, Nicotinamide Forms:

1. Nicotinamide nucleotides – nicotinamide adenine

dinucleotide (NAD) and nicotinamide adenine

dinucleotide phosphate NADP (active forms of B3) in

animal products

2. Nicotinic acid in plant sources

3. Bound covalently to complex carbohydrates (called

niacytin) e.g. in corn (10% absorption)

4. Bound to small peptides called niacinogens

5. Synthesised in the liver from tryptophan (also requires

B2,B6 and iron - agonists)


Vitamin B3 Digestion & Absorption

Absorption via Na+ dependent carrier-

mediated diffusion

Concentration dependent:

conc. = Na+ dependant

conc. = Passive diffusion (3-4g dose)

Within intestinal tract or enterocytes:

Glycohydrolase

NAD and NADP Nicotinamide

Nicotinamide and nicotinic acid can be

absorbed in the stomach but more

readily absorbed in the small intestines.

Alcohol inhibits the absorption.




Vitamin B3 Transporto In plasma, Vitamin B3 is primarily found as nicotinamide (15-

30%) but nicotinic acid can also be found (bound to plasma

proteins).

o Vitamin B3 crosses into cell membranes via simple (passive)

diffusion

o In the kidneys and red blood cells, nicotinic acid can only

move into the cells via facilitated diffusion and in brain via

active transport.

o Higher concentrations are found in liver, kidneys and brain.

Storage:

o Nicotinamide serves as the primary precursor to NAD which is

synthesised in all tissues (mitochondria).

o Excess niacin and tryptophan is converted to NAD which is

stored in small amounts.


Revision Questions

o Name the two active coenzyme forms of niacin?

o Vitamin B3 may also be synthesised in the liver from

which amino acid?

o What other nutrients are required in this conversion?

o By which two mechanisms do B3 get absorbed from the

intestine?


Pantothenic Acid – Vitamin B5Sources:

Widely distributed in

nearly all plants and

animal products,

therefore a deficiency is

highly unlikely.

Key sources include:

o All meats esp. liver

o Mushrooms

o Egg yolk

o Legumes

o Whole grains

o Broccoli

o Avocado

o Royal jelly

Pantothenic Acid Forms:

o In supplements, it is usually found

as calcium pantothenate;

o 85% found in foods are bound as a

component of coenzyme A (CoA).

o B5 is easily destroyed with heating

and freezing.


Pantothenic Acid Digestion & Absorption

In digestion CoA is hydrolysed

CoA Pantetheine Pantothenic acid

NB: Panthothenate absorption has been shown to decrease to about 10%

when pantothenate ingestion approaches 10 times recommended intake in

pill form.

Primarily absorbed in jejunum

Conc. = Passive diffusion

Conc. = Na+ dependent multivitamin

transporter (SMVT – shares with biotin

and lipoic acid)

Approx 50% ingested B5 is absorbed




Pantothenic Acid Absorption

Mostly transported via RBC’s

(passive diffusion)

And

Some free form in the plasma

B5

Facilitated diffusion

Na+ dependent (SMVT)

Liver Heart

Brain MuscleAll other cells


Pantothenic AcidIn cells – Pantothenate may accumulate and is typically

used to synthesise and re-synthesise CoA.

Found in high concentrations (storage):

o Heart

o Liver

o Adrenal glands

o Kidneys

o Brain

o Antagonist – Alcohol, Diabetes mellitus and IBS.


Revision Questions

o Is the absorption mechanism of B5 concentration

dependent?

o What is the coenzyme form of pantothenate?

o How is B5 mainly transported in circulation?

o In cells, what is B5 typically used for?


Pyridoxine – Vitamin B6

Sources: Sirloin steak, salmon, vegetables, navy beans, whole grains, bananas, chicken, walnuts

Formso Non-phosphorylated forms

o Pyridoxine (PN) – most stable form, mostly found in plants,

o Pyridoxal (PL)

o Pyridoxamine (PM)

o Phosphorylated forms

o Pyridoxine phosphate (PNP)

o Pyridoxal phosphate (PLP)

o Pyridoxamine phosphate (PMP)

o Stable with cooking, often lost in processing and storage.


Pyridoxine Digestion & Absorption

PN

PL

PM

Phosphorylated forms (PNP, PLP, PMP)

hydrolysed by

Alkaline phosphatase (Zn dependent)

or other phosphatases

at brush border to yield PN, PL or PM

o Absorption of PN, PL and PM occurs primarily in the

jejunum by passive diffusion

o The free forms of B6 are absorbed rapidly

o In high concentrations the phosphorylated forms may be

passively absorbed WITHOUT dephosphorylation

o Metabolism takes place in liver

o Most PLP in plasma is bound to albumin


Pyridoxine Transport

The liver is the main organ of metabolism of B6

o PNP may be converted to PLP in the liver

FMN (B2)- dependent oxidase

PNP PLP Agonist – B2

Antagonist - Alcohol

PL PLP PL

ATP ADP

APLPL

PLP

PN PNP

ATP ADP

PM PMP

A

AB

C

A

B

C

Kinase (ATP)

PMP & PNP oxidase

Phosphatase


Pyridoxine Storageo Muscles represent the major storage (75 – 80%) site.

o Liver stores about 5-10%

o Binding of the vitamin to phosphates prevents its diffusion out

of the cell

o Binding to protein prevents hydrolysis by phosphatases

Highest concentrations of pyridoxine are found in the:

o Muscles and Liver

o To a lesser extent intestines, kidneys, brain and red blood

cells

o Found in all cells but in a lower concentration as some lack

sufficient oxidase for conversion


Revision Questions

o Name the three phosphorylated coenzyme forms of

pyridoxine?

o These phosphorylated forms require hydrolysis prior to

absorption into the enterocytes, what is the name of the

enzyme responsible for this and which nutrient is it

dependent on?

o What is the active form of B6 known as?

o Which vitamin is an agonist of B6?

o How is B6 absorbed across both the brush and

basolateral border?


Cobalamin – Vitamin B12Sources

o Primary dietary forms are found in animal products.

o All naturally occurring B12 is produced by microorganisms.

o Any plant form could be traced back to contamination with microorganisms e.g. manure or nitrogen-fixing bacteria (legumes).

o Therefore only present in a few plant-based foods such as fermented legumes (tempeh) and vegetables (sauerkraut), nori and certain mushrooms (black trumpet) (Watanabe,

Yabuta,Tanioka & Bito 2013).


Vitamin B12

Sources

o Meat and meat products

o Poultry

o Fish

o Shellfish (esp. clams, oysters)

o Eggs

o Milk and milk products

o Dairy foods contain less B12 but may be more bioavailable.

o B12 is fairly stable and resistant to light, heat and

oxidation.


Cobalamin – Vitamin B12

B12

Ileal receptor

(requires Ca)

B12+ R

B12• R

complex

B12• R

B12

B12• IF B12• IF

B12

R proteins

(Heptocorin)IF

IF

IF

IF

IFR

Small IntestinePyloric

sphincter

Stomach

Newly absorbed B12 will be

transported in blood bound to

TCII B12


Vitamin B12

Digestion & Absorption

1. Firstly B12 is released from peptide bonds in foods by the

gastric enzymes pepsin and hydrochloric acid

2. The R proteins, collectively known as cobalophilins or

haptocorrins (HC’s) are found in saliva and gastric juices and

can bind to B12 before it is released from food

3. Intrinsic factor (IF) is a glycoprotein synthesised by the

gastric parietal cells, but functions in the small intestines to

aid B12 absorption


Vitamin B12

Digestion & Absorption

4. In the small intestines, proteases hydrolyse R protein bound

to B12 to free the B12 (Therefore, pancreatic insufficiency

protease levels = B12 absorption). The R protein may

protect B12 from use by bacteria

5. In the proximal small intestine, IF binds with B12 once it is

released from the R protein

6. The IF-B12 complex travels to the ileum where specific B12

receptor sites (cubilins) are located. Absorption of B12 occurs

at these receptors sites throughout the ileum, especially the

distal third

7. This attachment triggers endocytosis of the complex, where

IF is then released within the enterocyte.

8. The B12 binds to transcobalamin 2 (TCII) in portal circulation


Factors that affect B12 absorption Antagonist

o Vitamin C in doses of 500mg or more take with meals and up

to 1 hour after a meal, may diminish or destroy the B12 in

food.

o Iron

o Folic acid

o Malabsorption syndromes

o Pernicious anaemia

o Pancreatic insufficiency

o Veganism

Agonist

o Calcium is required for B12 absorption.


Factors that affect B12 absorption

o IF mediated absorption reaches saturation at about 1.5-

2.0g/ meal

o Overall absorption is approx. 50% but decreases with

high intake.

o Pharmacological doses of B12 are absorbed via passive

diffusion throughout the intestinal tract

o B12 absorption is very slow.

o After the attachment of IF-B12 complex to the receptor,

there is a 3-4 hour delay before the cobalamin appears

in the circulation. Peak B12 levels in the blood may take

up to 8 – 12 hours after ingestion

o Microbiome also produces small amount of B12.


Cobalamin – Vitamin B12o Dietary supplements

Is usually present as cyanocobalamin, a form that the

body readily converts to the active forms

methylcobalamin and 5-deoxy-adenosylcobalamin.

o Dietary supplements can also contain methylcobalamin

and other forms of vitamin B12.

o Absorption rates don’t vary significantly between forms

and is largely limited by the capacity of intrinsic factor.

o About 10 mcg of a 500 mcg oral supplement is actually

absorbed in healthy people.

o Vitamin B12 – Evidence to date suggest no difference in

efficacy between oral and sublingual forms.


Vitamin B12

o Note - B12 can be recycled.

o Enterohepatic circulation is very important for B12. A

certain amount (3-8 g/day) is secreted into bile and

intestinal secretions which bind to IF and are

reabsorbed in the small intestine.

o Malabsorption (e.g. in Crohn’s disease) can affect B12

absorption greatly due to absorption site and thus also

impacts enterohepatic circulation which increases the

B12 requirement for people with these conditions.


Vitamin B12 Transport

B12

TC1 (~80%)

TCII (20%)

TCIII (<10%)

Circulating

Storage

Cells

RBC’s

Liver

From peripheral

tissues

Receptor

dependent

TC = Transcobalamins (also considered R proteins)

Heptocorrin (TCI) is the circulating storage of B12 and

may prevent bacterial use of vitamin.


Vitamin B12In the blood:

(i) 60-80% B12 is in the methylcobalamin form

(ii) 20% B12 is in the adenosylcobalamin form

(iii) Other forms include cyanocobalamin and

hydroxocobalamin

o Metabolism of the various forms of B12 occurs within

cells e.g.

Reduction utilising ATP

(in mitochondria)

AdenosylcobalaminHydroxocobalamin

Cytosolic Methylation

MethylcobalaminHydroxocobalamin


Vitamin B12

Storage

1. Unlike other B vitamins, B12 can be stored in the body

for years

2. It is mainly stored in the liver as the

adenosylcobalamin form.

3. It can also be stored in muscles, bone, kidneys, brain,

heart, spleen and circulating blood.

4. The B12 forms of hydroxocobalamin and

methylcobalamin are stored to a lesser extent


Revision Questions

o How is B12 released from peptide bonds in foods?

o What is the name of the substance which is found in saliva and

gastric juice that can bind to B12 before it is released from food?

o What is the name of the glycoprotein synthesised by the gastric

parietal cells, although functions in the small intestine to aid B12

absorption?

o Describe the process by which these two substances aid B12

digestion?

o Which mineral is required for B12 absorption?

o Which 2 nutrients may antagonise B12 if supplemented at the same

time?

o What is the major storage form of B12 in the liver?

o B12 travels in circulation bound to what?


Folate (Folic Acid)

Sources

Mushrooms

Green vegetables

Spinach

Brussels sprouts

Broccoli

Asparagus

Turnip greens

Peanuts

Legumes

Citrus fruits

Liver

FormsThere are over 150 different forms of

folate.

Structure made up of 3 parts:

i. Pteridine

ii. PABA

iii. Glutamic acid

o Pteroyl-monoglutamate – are the forms used in supplements (most stable form)

o Pteroyl-polyglutamate – is the primary form found in foods. They contain up to 9 glutamate residues


Folate Digestion & AbsorptionPolyglutamate forms

Conjugases Zn

Monoglutamate forms

Jejunal mucosa

• Conjugases hydrolyse polyglutamate forms of folate to

monoglutamate forms necessary for absorption

• Conjugases are found in bile, pancreatic enzymes and

on the brush border of jejunal mucosa

o The conjugases are zinc dependent, therefore, zinc

deficiency impairs the activity.

•Defects in PCFT result in folate malabsorption.

MGM

folatepH (5-6) FBP’s

Absorption occurs throughout SI,

but more in jejunumProton coupled

folate

transporter

(PCFT)


Folate absorption

o Raw foods are higher in folates than cooked foods.

o The enzyme that hydrolyses dietary folates are also

known as folylpoly-γ-glutamate carboxypeptidase

(FGCP)/Conjugase, is found on the luminal brush

border membrane in the human jejunum.

o Agonists – Zn, B3, FBPs

o Antagonists are Conjugase inhibitors – Alcohol,

legumes, lentils, cabbage, oranges


Folate absorption o Fortified foods are in monoglutamate forms, therefore

readily absorbed.

o Absorption is enhanced in acidic condition.

o Uptake of folate into liver and other tissues is carrier

mediated, mainly by, reduced folate carriers (RFC).

o Within intestinal cells, THF, converted to methyl-THF and

converted to either 5- or 10-formyl THF dependent on

NADPH.

o In systemic blood, it is found as free form or bound to

albumin, α-2 macroglobulin and a folate binding protein.


Folate Transport

FolateNAD

Dihydrofolate (DHF)

NAD

THF

(Methylated)

5-methyl THF

FBP’s+ folateFBP’s+ folate

5-methyl THF

Some MGM, DHF

Reduced Folate

Carrier mediated

(RFC)DHF

THF

Folate circulates in the blood

predominantly as 5-methylTHF.


Revision Questions

o What are the three substances which make up folic

acid?

o Folate exists primarily in foods in polyglutamate forms

which need to be hydrolysed into monoglutamate forms

prior to absorption into enterocytes. Name the group of

enzymes responsible for this and what nutrient are they

dependent on?

o Name 3 factors which may inhibit the absorption of

folate?

o How does the majority of folate travel through

circulation?


Biotin

Sources

Widely distributed in foods

Liver Soybeans

Egg yolks Cereals

Legumes Nuts

o Biotin also produced by colon bacteria and absorbed in proximal

and mid transverse colon, however, this form doesn’t meet the

needs of a human

o Avidin, a glycoprotein in raw egg white may irreversibly bind biotin

in a non-convalent bond and prevent biotin absorption

o Avidin is unstable with heat, therefore ingestion of cooked egg

whites does not compromise biotin absorption


Biotin Digestion & Absorption

Protein bound Biotin

Proteases

Biotin,

Biocytin

or Biotinyl

peptides

Proteases

Biotin

Biotinidase

Mostly absorbed in the

jejunum and also in the ileum

Lysine

Biotin

Na+

Na+

Na+

Biotin


Biotin Digestion & Absorption

• Absorption is via SMVC or SMVT (Sodium

dependent multi-vitamin carrier or transporter)

shared with B5 and lipoic acid.

• Passive diffusion occurs at pharmacological doses.

• Transport across basolateral border is carrier

mediated but not sodium dependent.

• Alcohol inhibits intestinal biotin absorption

(antagonist).

• Biotin is found in plasma in a free unbound form.

Some bound to proteins.


Biotin dependent enzymes

(Gropper & Smith, 2016).


Revision Questions

o Where is biotin endogenously produced?

o What substance can inhibit intestinal absorption of

biotin?


Activity – Make your own tableNutrient Coenzyme

Forms

Digestion Absorption Transporte

r proteins

Highest

Storage

Metabolism Agonist Antagonist

Brush

border

Basolater

al border


Nutrient control of gene expression o Most of this DNA is found in the nucleus whereas a small

amount is found in the mitochondria.

o DNA holds the code for the amino acid sequence of

every protein in the body.

o DNA is composed of four bases: adenine, guanine,

thymine, and cytosine.

o A change in the sequence of the nucleotides within the

DNA, the sequence of amino acids in the resultant

protein could be different. In some instances, there may

be no or limited metabolic consequences.

o These genetic differences are termed polymorphisms

and can effect the expression of subsequent enzymes.


o The bases that

make up the DNA

polynucleotide

chain are joined

together by

phosphodiester

bonds using ribose

as the common link

between the bases.


Nutrient control of gene expression o The synthesis of the bases that make up the DNA is

dependent on the micronutrients as well as on energy.

Folacin, pyridoxine, Vitamin B12, iron, copper, sulphur,

zinc, magnesium, and phosphorus are all needed to

synthesise these purines and pyrimidines.

o Should any of these nutrients be in short supply, cells

with short half-lives such as epithelial cells and blood

cells will not be replaced as readily. Thus, such

micronutrient deficiencies are often characterised by skin

lesions or anaemia.

o DNA damage, whether spontaneous or caused by

external agents, can be repaired in the nucleus but the

mitochondrial DNA has little self-repair.


Nutrient control of gene expression o Sometimes repair is inaccurate, a base addition,

substitution or mismatch repair could occur.

o This mutation will then become part of the genetic

information transmitted to the next generation.

o Heritable changes in gene expression can occur without

a change in the sequence of the DNA. This is called

epigenetics.

o In the nucleus, the DNA is found in the chromosomal

chromatin. Chromatin is a protein-rich material that

surrounds nuclear DNA. The proteins are both histone

and non-histone proteins.


Nutrient control of gene expression o The amino acid residues in the histone tails are modified by

covalent acetylation, biotinylation, methylation,

phosphorylation, and ubiquitination which in turn can further

alter the gene expression.

o DNA methylation, acetylation and histone modification may be

limited as a result of environmental change that can include

changes in nutrition status.

o The modification of DNA also depends on a number of other

nutrients, including S-adenosyl methionine, vitamin B12,

pyridoxine, methionine, betaine, riboflavin, zinc, and choline.

o It is clear that nutritional status can exert epigenetic effects on

gene expression.

o Examples of this include caloric restriction, starvation, nutrient

deficiency, and effects of ageing on nutrient availability.


ReferencesAllen, P. (Eds.). (2013). Encyclopedia of human nutrition. Retrieved from

http://www.credoreference.com

Berra, E., Ginouvès, A., & Pouysségur, J. (2006). The hypoxia-inducible-factor

hydroxylases bring fresh air into hypoxia signalling. EMBO Reports, 7(1), 41-

45. Retrieved from http://www.ebscohost.com

Gropper, S. S., & Smith, J. L. (2016). Advanced nutrition and human metabolism (7th

ed.). Belmont, CA: Wadsworth Cengage Learning.

Hoey, L., Strain, J. J., & McNulty, H. (2009). Studies of biomarker responses to

intervention with vitamin B-12: a systematic review of randomized controlled

trials. The American Journal of Clinical Nutrition, 89(6), 1981S-1996S.

doi:10.3945/ajcn.2009.27230C

McMurry, J. (1992). Organic chemistry (3rd ed.). Pacific Grove, CA: Brooks/Cole

Publishing Company.

Marks, D. B., Marks, A. D., & Smith, C. M. (1996). Basic medical biochemistry – a clinical

approach. Baltimore, MD: Lippincott Williams & Wilkins.

Osiecki, H. (2002). Cancer: A nutritional/biochemical approach. Eagle Farm, QLD:

Bioconcepts Publishing.


References

Patak, P., Willenberg, H. S., & Bornstein, S. R. (2004). Vitamin C Is an Important Cofactor

for Both Adrenal Cortex and Adrenal Medulla. Endocrine Research, 30(4), 871-

875. doi:10.1081/ERC-200044126

Roach, J. (2003). Metabolism and Nutrition (2nd ed.). London, England: Mosby.

Shils M. E., Olson, J. A., Shike, M., & Ross, A. C. (2006). Modern nutrition in health and

disease (9th ed.). Baltimore, MD: Lippincott Williams & Wilkins.

Varela-Moreiras, G., Murphy, M. M., & Scott, J. M. (2009). Cobalamin, folic acid, and

homocysteine. Nutrition Reviews, 67(Suppl. 1), S69-S72. doi:10.1111/j.1753-

4887.2009.00163.x

Watanabe, F., Yabuta, Y., Tanioka, Y., & Bito, T. (2013). Biologically active vitamin B12

compounds in foods for preventing deficiency among vegetarians and elderly

subjects. Journal Of Agricultural And Food Chemistry, 61(28), 6769-6775.

doi:10.1021/jf401545z


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