CHAPTER I

INTRODUCTION

BAB I
PENDAHULUAN

1. BACKGROUND

LATAR BELAKANG

Human genetics is the science that looks at the inherited variations in humans, a
study of the mechanisms of evolution, and the process of change in gene
frequency. Medicine is the application of these principles to health. Medicine is
passing through a revolution in how diseases are diagnosed, classified and
treated as a result of the advances in genetics. Equally, nutrition is significantly
the science of health, the study of how food fortifies and sustains the normal
individual. Many genetic differences relate to rare conditions. The challenges
are the explanation of the causes of common conditions that are secondary to
disease causing mutations, and the relationship between the genetic make-up of
individuals and populations and the environment and diet of the individual.

Every individual has a specific potential for survival and reproduction that is
dictated in part by genetically determined characteristics which influence
metabolism, fecundity, birth, growth and death.

2. PROBLEM FORMULATION

RUMUSAN MASALAH

a. How is the genetic pool in a town, district or country that you know
changing through immigration or emigration?

b. Apa saja jenis jenis vitamin dan cara kerjanya?

3. PURPOSE OF THE DISCUSSION

TUJUAN DISKUSI

a. To know that genetic can change the immigration or emigration pool

in a town, district or country.

b. Untuk mengetahui jenis jenis vitamin dan cara kerjanya.

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 CHAPTER II
CONTAIN

BAB II
PEMBAHASAN

A. GENETICS

1. PRINCIPLES OF INHERITANCE

Mendel clarified the process of inheritance through his studies on peas. In

the mating process, paired genes from each parent separate (segregate) into
single units, which pass to the next generation as individuals, independently of
each other, and are never present together in the next generation. Mendel
showed that when the newly paired genes from the parent generation are either
both dominant or both recessive the offspring will be homozygous for that gene.
If there is a mix of dominant and recessive genes the resulting individual is
heterozygous. Homozygous is when there are two identical genes at a single site
or locus of a chromosome; heterozygous is when these two genes are different.

Major genes have defined functions that determine spe- cific

characteristics, as distinct from polygenes, which are a group of genes
functioning together, each of which has a small but additive effect on the
phenotype. Major genes function at a single locus and may function in different
allelomorphic states.

Alleles may be:

• completely dominant

• incompletely or partially dominant; the pheno- type of the heterozygote

is intermediate between that of the two homozygotes

• codominant and contribute equally to the phe- notype.

According to Mendel’s second law, in the second generation alleles assort

independently so that equal numbers of each of the four types of gamete are
produced. Two general types of offspring are produced:

• two parental types

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 • a recombinant type where the dominant of one parent and the recessive
of the other parent are combined.

After conception, when two sets of chromosomes pair, the pairs of alleles
determine the character- istics of the developing individual. Some inherited
characteristics are probably dependent on several alleles; that is, there is a
cumulative influence of several genes. Genes close together on a chromo-
some tend to remain close to each other during cell division (gamete
production).

2. POPULATION OF GENETIC

Selection is a complicated process in a population and depends on

differential survival at any stage of the developmental cycle. Selection
processes in populations involve either elimination by loss for whatever reason
or failure to breed. Gradually, there are changes in the polymorphism as
beneficial traits aid survival and population increases. The newly formed
fertilised egg (zygote) develops into a baby, an infant and then an adult. Each
stage is vulnerable to the influence of environmental factors on the phenotype
for survival. Nutrition is a key influence in this process.

J.B.S. Haldane used birth weights to look for indications of selection in

human survival. Those babies with an optimal birth weight between 3.4 and
3.9 kg had a survival rate of 98.5%. The majority of those who died weighed
significantly more or less than the optimal, demonstrating a selection process
at the beginning of life.

J.B.S. Haldane used birth weights to look for indications of selection in

human survival. Those babies with an optimal birth weight between 3.4 and
3.9 kg had a survival rate of 98.5%. The major- ity of those who died weighed
significantly more or less than the optimal, demonstrating a selection process
at the beginning of life.

In the Middle Ages in Europe the plague was rampant; in the 19 century,
tuberculosis was common – this disease is associated with some candidate
genes human leucocyte antigen presentation, the divalent cation transporter
gene and the vitamin D receptor gene, and in the 21 century and today, coronary
artery disease and cancer are the main killer diseases with associated candidate
genes (see Chapter 47).

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The present Western generation has a wide dietary choice, clean food, good
sanitation, attractive accommodation and relative freedom from lethal
infectious diseases. The population is, however, exposed to an abundance of
food, tobacco smoking, industrial pollution, viral and prion infections, and
sedentary occupations. The population that survives a particular epidemic may
be at a genetic advantage, but those genetic characteristics that enable survival
in one stress situation may create a subsequently more vulnerable population in
another stress situation

B. VITAMIN

1. NOMENCLATURE AND CLASSIFICATION OF VITAMINS

The classification of vitamins may be as water and fat soluble, or according to

function as blood forming, antioxidant, involved in energy or protein
metabolism, or bone forming. These classifications are important from the
historical perspective and belong to a brilliant period of discovery in nutri-
tion. The deficiency conditions or diseases that brought vitamins to the
attention of scientists were regarded as central to the action of the vitamins.
The identification of the role of vitamins as coen- zymes and with hormone-
like actions supersedes all of these classifications.

Therefore, the vitamins are described individu- ally, with the exception of the
metabolically inter- connected folic acid, vitamin B 12, choline and methionine
system.

The water-soluble vitamins are vitamin C (ascorbic acid), vitamin B 1 (thiamin),

nicotinic acid (niacin) and nicotinamide, riboflavin, vitamin B 6 (pyridoxine),
pantothenic acid, biotin, folic acid and vitamin B12 (cyanocobalamin). The fat-
soluble vitamins are vitamin A (retinol), vitamin D (cholecalciferol), vitamin K
and vitamin E (tocopherols). Vitamins may be single chemical entities, e.g.
ascorbic acid, or consist of a family of closely related compounds, e.g. vitamins
A, D, K, E and B12.

The classification of vitamins becomes more dif- ficult as an understanding of

their action increas- es. Vitamins may have actions that are important in blood
formation (folic acid and vitamin B12), as antioxidants (ascorbic acid and
vitamin E), and in energy metabolism (thiamin, riboflavin and pyri- doxine),
bone formation (vitamin D) and protein metabolism (vitamins A and K). Some
vitamins act specifically as coenzymes (Table 16.1). Nuclear receptors for

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vitamins A and D belong to the nuclear hormone receptor superfamily and act
as ligand-inducible transcription factors.

The lipid-soluble vitamins have less easily defined functions. Vitamin D can be
synthesised in the skin and has many similarities to a hormone, its influ- ences
extending further than its function in bone formation. Vitamin A, as a pigment–
protein com- plex, acts as an absorber of light in the eye. Vita- mins D and A
act on a variety of receptors, which are now beginning to be understood.
Vitamin K, important in clotting reactions, is also involved in the formation of
g-carboxyglutamate in a number of processes that involve calcium and calcium-
regulated metabolic processes.

2. FACTORS INFLUENCING THE UTILISATION OF VITAMINS

a. Bioavailability

Not all vitamins may be ingested in an absorbable form in the intestine, e.g.
nicotinic acid derived from cereals is bound in such a way that it is not
absorbed. Fat-soluble vitamins may be malabsorbed if the digestion of fat is in
any way impaired.

b. Water solubility

The intestinal absorption of vitamins is by specific pathways, many of which

are sodium dependent. In some instances, absorption includes chemical
change, e.g. phosphorylation, which is a feature of the absorption process of
riboflavin and pyridoxine.

c. Antivitamins

These are present in natural food. Several synthetic analogues of vitamins are
highly poisonous, e.g. aminopterin, tesoxypyridoxine. These substances inhibit
the activity of true vitamins and enzyme systems.

d. Provitamins

These, although not vitamins themselves, can be con- verted to vitamins in the
body. Carotenes are provi- tamins of vitamin A, and the amino acid tryptophan
can be converted to nicotinic acid. Vitamin D is syn- thesised in the skin by the
action of sunlight on a derivative of cholesterol. Because vitamins have tra-
ditionally been regarded as dietary constituents, it is anomalous that vitamin D

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is synthesised in the skin in response to sunlight. In some respects vitamin D
could better be regarded as a hormone.

e. Biosynthesis in the gut

The normal bacterial flora of the gut can synthe- sise some vitamins, e.g.
vitamin K, nicotinic acid, riboflavin, vitamin B12 and folic acid. Because these
are synthesised in the colon it may be that they are not nutritionally relevant, as
they may not be absorbed.

f. Interaction with nutrients

An example of this phenomenon is a diet rich in carbohydrates and alcohol

requiring additional thiamin for the body’s metabolic requirements. Similarly,
when there is a high intake of polyun- saturated fats, vitamin D requirements
are increased.

3. VITAMIN A

a. INTRODUCTION

Vitamin A consists of a group of biologically active compounds closely

related to the plant pigment carotene. The carotenoid family consists of
approximately 100 naturally occurring pigments, which provide the yellow–red
colour of many vegetables and some fruits. B Carotene, a pro vitamin A, has
widespread distribution in plants and is associated with chlorophyll. It is unique
in that it is the only carotenoid in which both halves of the molecule are
identical to retinol. Other carotenoids, e.g. xanthophyll, which is another yellow
pigment associated with chlorophyll, and lycopene, the red pigment of
tomatoes, do not have pro vitamin A activity.

Retinol is present in milk, butter, cheese, egg yolk, liver and fatty fish.
The liver oils of fish are the richest natural source of vitamin A. Carotenes are
found predominantly in green vegetables associated with chlorophyll. The green
outer leaves of vegetables are a good source of carotenes, where as white inner
leaves contain little. Yellow and red fruits and vegetables, particularly carrots,
are good sources. Vegetable oils, with the exception of red palm oil, which is
found in west Africa and Malaysia, do not contain vitamin A. Retinol is present
in breast milk.

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 b. ACTION OF VITAMIN A

Vitamin A is essential for the growth and normal function of the retina, and the
development of epithelial surfaces in the retina. Recent discoveries have shown
that most actions of vitamin A in development, differentiation and metabolism
are made possible by nuclear receptor proteins that bind retinoic acid, the
active form of vitamin A.

These form dimers and bind to DNA, and regulate many developmental control
genes including home box genes and growth factor genes. Gene transcription
is induced by interacting with promoter sequences on the target gene, and
modulated by nutritional and hormonal activity. The acid isoforms affect a wide
diversity of biological systems, lymphoid cells, nerve and muscle cells, as well
as developmental programmers. Retinoids have a role in the development of
the the central body axis and limbs of the foetus. As an excess leads to gross
abnormalities in the infant, the balance is important.

c. AVAILBILITY OF VITAMIN A

The first step in vitamin A metabolism is the absorption or uptake of retinol

from the intestine. Retinyl esters are hydrolysed in the small intestine by
pancreatic hydrolases or an intestinal brush border hydrolase. The retinol is
made more solu- ble by inclusion in a micellar system. Absorption requires a
saturable passive carrier-mediated system.

After absorption, retinol is esterified with long- chain fatty acids. This reaction
is catalysed by two microsomal enzymes:

• lecithin: retinol acyltransferase (LRAT), which uses the sn-1 fatty acid of
phosphatidylcholine as the fatty acid donor

• acyl-CoA: retinol acyltransferase (ARAT), which uses acylated free fatty

acids.

Vitamin A is stored as retinyl esters with long- chain fatty acids in animal
tissues, especially the liver. Release from the liver is in the form of retinol; this
circulates bound to a specific transport protein, retinol binding protein, which
forms a complex with plasma pre-albumin. These can be measured by
immunoassay. Concentrations are low in mal- nourished children. After
ingestion, 8% of retinol is absorbed, 30–50% is stored in the liver, and 20–60%
is conjugated and excreted in bile as a glucuronide. Stores of retinol are

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substantial, around 400 mg, and last for many months, even years. There is
almost certainly an enterohepatic circulation of retinoids, since retinoyl b-
glucuronides and other retinoid metabolites are found in bile.

C. VITAMIN ADEFICIENCY

The clinical effects of vitamin A deficiency are usually seen only where the diet
has been deficient in dairy produce and vegetables over a prolonged period, or
in mal-absorption syndrome.

Vitamin A is involved in the maintenance of epithelial surfaces, and a

deficiency leads to epithelial metaplasia in the respiratory tract, mucous
membranes (especially the eyes), gastrointestinal tract and genitourinary tract.
The mucosa is replaced by inappropriately keratinised stratified squamous
epithelium. In the skin, vitamin A deficiency results in keratinisation, which
blocks the sebaceous gland with plugs, producing a condition known as
follicular keratosis.

In vitamin A deficiency the epithelial cells of the cornea develop squamous

metaplasia. Its clinical forms are:

• conjunctival xerosis

• corneal xerosis

• keratomalacia: leads almost certainly to blind- ness

• night blindness: an early symptom of vitamin A deficiency; may occur

without any evidence of xerophthalmia

• xerophthalmic fundus corneal scars.

D. RECOMMENDED REQUIREMENTS

1) Adults

For the average adult the estimated average requirement (EAR) of 500 mg/day
for a 74 kg male and 400 mg/day for a 60 kg female is reasonable. The lower
reference nutrient intake (LRNI) is 300 mg/day for men and 250 mg/day for
women; the reference nutrient intake (RNI) is 700 mg for men and 600 mg for
women.

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 2) Infancy

The recommended daily amounts (RDAs) for infants are usually based on the
vitamin A provid- ed by breast milk. A daily intake of 350 mg retinol
equivalents meets a young child’s requirements, allowing for growth and
maintaining liver stores. This means the EAR is 250 mg/day and the LRNI 150
mg/day.

3) Children

Children are growing and require vitamin A for the body stores. The
recommended intakes are in the same order as for adults.

4) Pregnancy

In pregnancy extra vitamin A is required for the growth and maintenance of the
foetus, to provide reserves and for maternal tissue growth. This is par- ticularly
important during the third trimester. An increment of 100 mg/day during the
pregnancy, increasing the maternal RNI to 700 mg/day, should meet all
requirements. A word of caution: there are dangers with large intakes of
vitamin A (see below).

5) Lactation

The diet should contain an increment of 300 mg/day for milk production.

E. BODY STORE MEASUREMENTS

An alternative approach to the dose–response test is based on body size pool.

Adequate vitamin A status is defined in terms of an adequate body pool, based
on the amount of vitamin A in the liver, which contains the majority of vitamin
A in the body. A liver retinol concentration of 20 mg/g tissue is the basis of the
recommendations made by The Food and Agriculture Organisation (FAO) and
the World Health Organisation (WHO).

1. Vitamin A consists of a group of biologically active compounds closely

related to the plant pigment carotene. The carotenoid family con- sists of
approximately 100 naturally occurring pigments, which provide the
yellow–red colour of vegetables and some fruits.

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2. The retinol molecule consists of a hydrocarbon chain with a b-ionone
ring at one end and an alcohol group at the other. The usual form is the
all-trans stereoisomer.

3. Vitamin A is essential for growth and normal function of the retina, and
development of epithelial surfaces in the retina. The photopig- ment
rhodopsin is a receptor protein found in the retinal rod cells. Rhodopsin
consists of a membrane-embedded protein, opsin, and a light-sensitive
pigment group, retinal.

4. Vitamin A and the retinoids act through nuclear receptor proteins, which
regulate gene transcription.

5. Vitamin A deficiency is an important cause of eye malfunction, night

blindness and xeroph- thalmia, a lesion of the conjunctiva and cornea.
Other epithelial tissues, e.g. skin, are also affected.

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