Exam 2 Flashcards
Cells acquire nucleotides through two processes:
de novo synthesis and
salvage pathways.
De novo synthesis of purines results in the synthesis of
inosine that can be
converted into adenosine and guanosine.
Atoms in a newly synthesized purine are derived from
several sources
including the amino acids aspartate, glutamine and glycine, methyl groups
supplied by folic acid and carbon dioxide.
ADP and GDP regulate de novo synthesis of
purines at multiple points in the
pathway.
Hypoxanthine and guanine can be recycled through
the salvage pathway
with Hypoxanthine guanine phosphoribosyl transferase (HGPRT).
Xanthine oxidase catalyzes a
hydroxylase type reaction leading to the
formation of uric acid that can be excreted.
Excess uric acid is the cause of
gout
Gout is most often caused by
low levels of secretion of uric acid, but can
also be caused by excess production.
Crystallization of Sodium urate in the joints leads to
a localized inflammatory
response.
Allopurinol, a purine analog, is used to treat
gout. It inhibits Xanthine
oxidase preventing the formation of uric acid.
A HGPRT deficiency causes
Lesch-Nyhan syndrome that results in severe
retardation, crippling gouty arthritis and self-mutilation.
Lesch-Nyhan occurs in males only because
the HGPRT gene is located on
the X chromosome.
The breakdown of purines can replenish TCA cycle intermediates through
the production of fumarate.
The atoms in a pyrimidine ring are derived from
aspartate and carbamoyl
phosphate.
The first 3 enzymes in the synthesis of pyrimidines are
located on the same
protein (CAD protein).
The pyrimidines U and C can be
interconverted
dUMP is converted to TMP by
thymidylate synthase, an enzyme requiring
the transfer of a methyl group from tetrahydrofolate.
Inhibitors of tetrahydrofolate production are used as
as therapeutic agents for
treating cancer and bacterial infections.
Fluro substituted pyrimidine analogs that inhibit thymidylate synthase are
used as anticancer agents.
Ribonucleotide reductase converts
ribonucleotides to deoxyribonucleotides
Base-pairing in DNA is
A-T and G-C. In RNA it’s A-U and G-C.
Homologous regions of DNA can be compared among different species to
determine
phylogenetic relationships
Closely related organisms contain
similar DNA compliments, however they
are often arranged differently on the chromosomes of each species
The living world is made up of 3 divisions, or domains
: bacteria, archaea and
eukaryotes.
There are 4 main processes for generating change in a genome
intragenic mutation (single base change), gene duplication, DNA segment shuffling, horizontal transfer (from one cell to another).
Bacterial genes are usually clustered into groups (operons) that are
transcribed as a single unit.
Eukaryotic genes are often broken up with regions of
noncoding DNA or
introns between regions of coding DNA (exons).
In a comparison of the same gene in several closely related species,
exons will generally be very similar (conserved), while the introns will vary in
size and content.
Bacterial chromosomes are densely packed with genes leaving very little
DNA that is non-coding.
Most of the DNA in higher eukaryotes including humans does not code for
proteins. Most of the human genome is made up of repeated sequences. Many of those sequences are mobile elements that can move around in the genome.
Bacterial chromosomes are
circular and eukaryotic chromosomes are linear
In addition to the human genome, the entire genomes of a
large number organisms have been completed including several bacteria that
are found in the oral cavity.
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It is possible to construct metabolic pathways and compare them with other
organisms by examining their
entire genome content
Genes can be grouped into families bases on similar (homologous)
sequences found in different organisms. Homologous sequences can be
found in
genes of the same organism that carry out different but similar
functions. Genes that have similar functions in very distantly related
organisms can have similar sequences (homology).
The phylogenetic relationships of different organisms can be compared by
comparing the DNA sequence of similar genes in the two organisms.
DNA polymerase is a
a DNA dependent (uses DNA as a template) DNA
synthesizing enzyme.
RNA polymerase is a
DNA dependent RNA synthesizing enzyme.
Reverse transcriptase is an
RNA dependent DNA synthesizing enzyme
Primase is a
DNA dependent RNA polymerase.
Primase synthesizes a
small RNA “primer” that can be used by the DNA
polymerase to elongate the chain.
DNA polymerase minimizes the number of mistakes
by using a 3’ to 5’ exonuclease (or proofreading) activity that is
part of the same protein.
DNA polymerase as well as all other nucleic acid polymerases synthesize
DNA in the
5’ to 3’ direction only.
During replication, each new nucleotide is added to the
3’ carbon on the last
nucleotide of the new DNA chain.
The base component of each nucleotide is connected to the sugar at the 1’
carbon. The adjacent nucleotides in a DNA chain are
attached at the 5’ and
3’ carbons. And the 2’ carbon differs between RNA and DNA. (see figure
below, you should be able to recognize each carbon from the figure)
DNA polymerase is an
elongating enzyme; it cannot initiate synthesis.
Therefore a primer is required for elongation of a new stand using the DNA
polymerase.
Bacterial chromosomes contain
one origin of replication
DNA synthesis proceeds in both directions away from the
origin until the two
replication forks meet at a specific sequence on the other side of the
chromosome.
In bacteria new rounds of DNA replication can begin
before the previous
round is completed.
Eukaryotic chromosomes contain many
origins of replication that may change
during the development of the organism.
In eukaryotes, each entire chromosome is replicated only
once each cell
division and new rounds of replication do not start until after the cell divides.
Eukaryotic chromosomes are
linear and special structures called telomeres
are placed on each end.
Telomeres are constructed with the enzyme
telomerase that uses an RNA
template to synthesize a short repeated DNA sequence at the ends of
chromosomes.
Because the polymerase must synthesize new DNA in the 5’ to 3’ direction,
the two polymerase molecules on opposite strands move
away from each
other.
Helicase
unwinds (separates) the 2 DNA strands before polymerization of the
new strands.
Single-stranded binding proteins keep the
two complementary strands for
reforming a double helix.
The polymerase on the leading strand moves toward
the replication fork and
the polymerase on the lagging strand moves away from it.
The lagging strand is synthesized in short
Okizaki) fragments
Primase initiates synthesis of each
Okizaki fragment by making a short RNA
primer.
The leading strand is synthesized by the
continuous movement of the DNA
polymerase along the template.
Methylation of the DNA signals that the DNA is
unreplicated and is ready to
be used as a template for the next round of synthesis.
New or modified genes can be generated by one or a combination of 4
events:
1) point mutations in the coding region that change the amino acid
composition of the protein. 2) duplication of the entire gene. 3) Mixing of
segments of one gene with segments of another gene – segment shuffling. 4)
Acquisition of new activities by transfer of genes between two organisms –
horizontal gene transfer.
Many genes belong to gene families that share
homologous regions. These
regions usually code for proteins that carry out similar functions.
Breaks in the DNA (especially double stranded breaks) facilitate
the initiation
of recombination.
A defect in DNA ligase, that affects
joining together of adjacent segment of
DNA on a chromosome, can cause abnormal amounts of recombination.
Recombination is the
reciprocal exchange of genetic information
Recombination can be the result OF
1) reciprocal exchange during cell
division. 2) DNA damage, e.g. X-ray damage. 3) Introduction of foreign DNA.
4) Programmed recombination during the development or maturation of a cell
type, e.g. antibody producing genes during B-cell maturation.
Gene conversion is the
non-reciprocal exchange of genetic information.
Recombination between
direct repeated sequences on the same
chromosome causes the loss of DNA that was between the two repeated
segments.
Circular DNA can be inserted in a
chromosome by recombination between a
region on of circular molecule and an homologous region on the
chromosome. (The reverse of #53).
X-rays and other agents that cause breaks in DNA induce
recombination
Transposable elements are found in
all species from bacteria to human
Transposable elements move from one
location in the DNA to another
location within that cell.
Transposable elements can cause changes
in the DNA at the site of
insertion.
There are two major types of transposable elements
one type that contains
inverted repeated sequences at the ends and causes a short region of the
genome to be duplicated at the site of insertion and a second type that is
structurally similar to a retrovirus and transposes through an RNA
intermediate.
Unequal crossing-over is
recombination that resulted from imprecise pairing
of tandemly repeated sequences.
Unequal crossing over results in
the loss or gain of gene copies.
There are two types of mutations
DNA rearrangements and base
substitutions.
There are many mechanisms in each cell for repairing
DNA
Damage to a nucleotide (e.g. deamination) can either be
repaired or lead to a
permanent mutation.
Mutations can be caused by either
errors during replication or by injury to the
DNA from chemicals or radiation.
A small fraction of every genome (about 3% in humans) is made up of
segmental duplications or large regions of DNA that are present in more than
one copy.
The duplicated DNA is generated by a process called
gene amplification
Gene amplification can result in
resistance to drugs, transformation into
cancerous cells or other changes in the cell phenotype.
Several human diseases are due to
defects in DNA repair enzymes.
The differences between fat-soluble and water-soluble vitamins.
Vitamins are classified into two groups: water-soluble and fat-soluble. Water-soluble vitamins, which include all of the B vitamins, are easily absorbed into the body. If you consume more of a water-soluble vitamin than you need, the excess will be excreted, not stored.
Measurements of vitamin levels in the blood relate more to
recent intake than to overall body status.
Water-soluble vitamins act as
coenzymes in many metabolic pathways
The body has no storage capacity for water-soluble vitamins– except
B12
Evidence is emerging that suggests an excess of some
B vitamins can be toxic
Most vitamins are modified before
they become active