Genetics, Nutrition

7/27/2019 Genetics, Nutrition

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Genetic biochemistry


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Replication Transcription

DNA RNA ProteinTranslation

DNA double helix

Nucleosome, histones

Solenoid structure

chromosome


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Replication: semiconservative


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The replication

Enzymes: - DNA-dependent DNA polymerase I

(repair), II (not clear), III (polymerase)

- Topoisomerase (helicase) unwinding,

girase a pos. -> neg. supercoil

- Primasesynthesis of RNA primer

- Ligase binds DNA fragments

Fourdeoxyribonucleoside triphosphates (dATP,

dGTP, dCTP, dTTP)


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Replication steps: Initiation

A dnaA protein is bound to the oriC region,

which is detached, helicase (dnaC protein) ->replication fork, primosome

SSB protein stabilizes the single strand DNA

Girase decreases the tension of the strandinduced by the helicase

Primase enhances the synthesis of the RNAprimer


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Replication steps: elongation

Polymerase III catalyzes the binding of dNTP-s to the3OH group of the ribose in the RNA primer, PPi isreleased

Pairs: A =T, CG, polymerase III controls it

The new strand is synthesized in 5 > 3 direction

Leading strand (continuous synthesis), lagging strandforms loops (Okazaki fragments)

The many RNA primers are decomposed by an enzymecomplex (DNA polymerase I) having RNAse andexonuclease activity

The gaps are filled by the polymerase I, the fragments are

linked together by ligase


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Replication: termination

Replication is bidirectional, it has multiple

origins

In case of the circular bacterial DNA the

process ends when the two bifurcations meet on

the opposite side compared to the ori region

Special proteins signal the end of thereplication, stopping the helicase activity


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Repair

Mutations are caused by UV light, dithymines areformed> xeroderma pigmentosum, it can lead

to skin cancer; germicid lamps are used NH2 group deamination: C -> U (preservatives)

Substitution, insertion, deletion

Mutations have regularly negative effect,sometimes give advantages or can be silent

Ames test: to evaluate the mutagenic effect -Salmonella typhimurium His requirement


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Transcription


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Transcription: steps

One DNA strand is transcripted

DNS-dependent RNA polymerase -> RNA synthesis, U

instead of T. In case of the coli bacteria the core of theenzyme 2, and subunits are also bound to it (

is important in the initiation)

Preinitiation: The enzyme is bound to the promoter

region of the DNA (5TATAAT3, 5TTGACA3),

unwinds the DNA segment, the first nucleotide (purin)

binds to the subunit


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Transcription steps

Initiation: the synthesis of the RNA molecule starts at the

5 end, PPi is released, the polymerase is detached from the

promotor region Elongation: the DNA unwinds, transcription bubble is

formed (20 basepair), the polymerase inhibits double strand

DNA formation

Termination: the factor protein recognizes the stop

region on the template DNA (or hairpin sequence), the

polymerase is detached from the DNA, dissociates


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Replication, transcription - differences

Ribonucleotides are necessary

U instead of T

No primer required

Only some DNA segments are transcripted,

while during replication the entire genom is

duplicated

Many mistakes are made, no efficient repair


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RNA processing

Exons: aminoacid codifying sequences

Introns: non-coding regions (cleaved out) Exons linked together

Adding or removing polynucleotide segments

mRNA, rRNA, tRNA formation, final functioncan be fulfilled


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Reverse transcription

RNA viruses (ex. HIV)

The genom is RNA, it is transcripted to DNA

(reverse transcriptase is necessary) RNA is decomposed from the RNA-DNA hybrid,

replaced by a DNA strand

The viral DNA is inserted in the DNA of the host

cell, can be transcripted, might be dormant Genes of retroviruses: gag (virus core), pol (protease,

integrase, reverse transcriptase), env (envelope),mutations are frequent


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Translation: aminoacid activation


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firstletter

5 end

Second letter thirdletter

3 end

U U C A G

U

C

AG

Phe

Phe

LeuLeu

Ser

Ser

SerSer

Tyr

Tyr

STOPSTOP

Cys

Cys

STOPTrp

C Leu

Leu

Leu

Leu

Pro

Pro

Pro

Pro

His

His

Gln

Gln

Arg

Arg

Arg

Arg

U

C

A

G

A IleIle

Ile

Met

ThrThr

Thr

Thr

AsnAsn

Lys

Lys

SerSer

Arg

Arg

UC

A

G

G Val

Val

ValVal

Ala

Ala

AlaAla

Asp

Asp

GluGlu

Gly

Gly

GlyGly

U

C

AG

The genetic code


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The genetic code

Universal

No spaces

Collinear

No interference

One meaning Redundant


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Posttranslational modifications

The first aa is cleaved out (Met, fMet)

Amino-, carboxy terminal end cleaved out

Collagene OH-ation (Lys, Pro)

Glikoproteins: carbohydrates are attached

Tyr sidechains + I2 thyreoglobuline

Hormone activation: prohormones

Formation of disulfide briges


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Mechanism of transcription regulation

structure genes

transcription

mRNA

translation

repressor protein

mRNA

-galactosidase permease transacetylase


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Inhibiting drugs

Doxorubicin inhibit DNA (used in the

treatment of leukemia)

Amanitin, phalloidin inhibits RNA elongation

Difteria toxin, puromycin, tetracyclin,

chloramfenicol, streptomycin inhibit protein

synthesis


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Biochemistry of digestion and

nutrition


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Digestion

Oral cavity: mucins in saliva, lysosim, absorption

of drugs, digestive enzymes

Stomach: gastric juice, cell types

Pancreas: zymogenes, active enzymes

Liver: bile

Small intestine: final digestion, absorption, APUD

Colon: water retention, K+, HCO3-


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Caries in infants

The resistance of the dental tissues to acids influencesthe occurrence of the caries.

Mineralization of the teeth in the fetus begins in thesecond trimester of the pregnancy, thus it is influenced

by the state of health of the mother, her diet and lifestyle Severe chronic diseases, metabolic disorders like

gestational toxicosis, endocrine pathology influence theunborn child, leading to multiple, painful caries.Prematurity, trauma at birth, chronic disease of theinfant have a bad influence

Caries are rare in infant that have been breastfed


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The parietal cell


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Treatment of ulcer

Antiacids: Al(OH)3, CaCO3

Secretion inhibitor: - receptor blockers (antiAck,

antihistamine)

- antienzyme drugs (carboanhydraseinhibitors, protompump inhibitors)

Mucosa protecters: - PG E derivatives

- bismuth derivatives Antibacterial: against Helicobacter pylori

Surgical treatment: resection of the stomach, vagotomia


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Nutrition

Carbohydrates: give instant energy, the best are those that

are absorbed slowly

Lipids: high energetic value, saturated/unsaturated fattyacids - source

Proteins: are necessary for the growth process, renewing

the tissues. The complete proteins are from animal sources.

High intake is in pregnant and breastfeeding women

Vitamins, fibres, bioactive substances, water


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Feeding the infant

Breastfeeding 4-6 months

Artificial: milk formulas

Mixed: mothers milk+ formula

Not under 1 year: avoid fruits with tiny seeds,

albumen, fish, peas, beans, apricot, cherry,

cucumber, corn, pork

Under 6 months avoid gluten

After 6 months Fe: liver, meat, egg yolk

Genetics, Nutrition

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