Humane Levenscyclus I – Samenvatting ‘Essential Cell Biology’ en ‘Levenscyclus van de Mens’
ESSENTIAL CELL BIOLOGY: CHAPTER 2 – CHEMICAL COMPONENTS OF CELLS
Amino acids are small organic molecules with a general formula. At a pH of 7 (in a cell), the amino
acids exist in their ionized form. The 20 amino acids are grouped according to whether their
sidechains are acidic, basic, uncharged polar or nonpolar. The α-carbon atom is asymmetric,
causing two stereo-isomers, L and D, of which L is the most common form.
Cells use amino acids to build proteins—polymers made of amino acids. The covalent bond
between two neighbouring amino acids in a protein chain is called a peptide bond, and the
resulting chain of amino acids is therefore also known as a polypeptide. The polypeptide always
has an amino group at one end (N-terminus) and a carboxyl group at its other end (C-terminus),
causing polarity.
The chemical diversity that the 20 standard amino acids provide is vitally important to the function
of proteins. The diversity is caused by side chains that form ions in solution and can therefore carry a
charge. Some amino acids are polar and hydrophilic, and some are nonpolar and hydrophobic.
DNA and RNA are built from subunits called nucleotides. A nucleotide consists of a nitrogen-containing base, a five-carbon sugar, and
one or more phosphate groups. The sugar can be either ribose or deoxyribose. The nitrogen-containing bases can be a pyrimidine
(cytosine, thymine and uracil, all deriving from a six-membered pyrimidine ring) or a purine (guanine and adenine, bearing a second,
five-membered ring fused to the six-membered ring). Each nucleotide is named after the base it contains. A base plus its sugar (without
any phosphate group attached) is called a nucleoside.
Adenosine triphosphate (ATP) is the most common energy carrier. ATP is formed through reactions that are driven by the energy
released from the breakdown of food. When de-binding the phosphate groups, energy is released.
Nucleotides serve as building blocks for the construction of
nucleic acids. There are two main types of nucleic acids, which
differ in the type of sugar contained in their sugar–phosphate
backbone. Those based on the sugar ribose are known as
ribonucleic acids, or RNA, and contain the bases A, G, C, and U.
Those based on deoxyribose are known as deoxyribonucleic
acids, or DNA, and contain the bases A, G, C, and T. The linear
sequence of nucleotides in a DNA or an RNA molecule encodes
genetic information. They however have different roles in the
cell. DNA acts as a long-term repository for hereditary
information, while single-stranded RNA is usually a more
transient carrier of molecular instructions.
,ESSENTIAL CELL BIOLOGY: CHAPTER 5 – DNA AND CHROMOSOMES
Chromosomes are threadlike structures in the nucleus that become visible as the
cells begin to divide. They contain DNA and protein, DNA carrying the genetic
information of the cell and protein controlling the DNA molecules.
A molecule of DNA (deoxyribonucleic acid) consists of two long polynucleotide
chains. Each chain is composed of four types of nucleotide subunits (A, T, C and G)
and the two strands are held together by hydrogen bonds between the base
portions of the nucleotides.
If we imagine that each nucleotide has a phosphate “knob” and a hydroxyl “hole”
(see figure A), each strand will have all of its subunits lined up in the same
orientation. The two ends of the strand can be easily distinguished, as one will
have a hole (3ʹ) and the other a knob (5ʹ). This causes polarity in a DNA strand.
All the bases are on the inside of the double helix, with the sugar–phosphate
backbones on the outside. For the members of each base pair to fit together within
the double helix, the two strands of the helix must run antiparallel to each other.
The antiparallel sugar–phosphate strands then twist around each other to form a
double helix containing 10 base pairs per helical turn.
Genetic information is encoded in the DNA sequence. Organisms differ from one another because their DNA molecules have different
nucleotide sequences and, consequently, carry different biological information.
The nucleotide sequence of genes in DNA spell out the linear sequence of amino acids in a protein. The function of a protein is
determined by its amino acid sequence. Gene expression is the process by which the nucleotide sequence of a gene is transcribed into
the nucleotide sequence of an RNA molecule and then translated into the amino acid sequence of a protein.
Large amounts of DNA are required to encode all the information needed to make a multicellular organism . Each human cell contains
about 2 meters of DNA; yet the cell nucleus is only 5–8 μm in diameter. In eukaryotic cells, the DNA molecules are packaged into
chromosomes. These chromosomes not only fit handily inside the nucleus, but, after they are duplicated, they can be accurately
apportioned between the two daughter cells at each cell division. The task of packaging DNA is accomplished by specialized proteins.
Amazingly, this DNA is folded in a way that allows it to remain accessible to all of the enzymes and other proteins that replicate and
repair it, and that cause the expression of its genes.
In eukaryotes, DNA is distributed among a set of different chromosomes. The DNA in a human nucleus is distributed over 23 (F) or 24
(M) different types of chromosomes. Each of these chromosomes consists of a single linear DNA molecule associated with proteins that
fold and pack the fine thread of DNA into a more compact structure. This complex of DNA and protein is called chromatin. In addition to
the proteins involved in packaging the DNA, chromosomes also associate with many other proteins involved in DNA replication, DNA
repair, and gene expression. With the exception of the gametes, human cells each contain two copies of every chromosome, one
inherited from the mother and one from the father. The maternal and paternal versions of each chromosome are called homologous
chromosomes (homologs). The only nonhomologous chromosome pairs in humans are the sex chromosomes in males. Each full set of
human chromosomes contains a total of approximately 3,2 × 109 nucleotide pairs compromising the human genome.
A gene is a segment of DNA that contains the instructions for making a particular protein or RNA molecule. Most of the RNA molecules
encoded by genes are subsequently used to produce a protein, but sometimes the RNA molecule is the final product. Like proteins,
these RNA molecules have diverse functions in the cell, including structural, catalytic and gene regulatory roles.
Chromosomes also contain a large excess of interspersed DNA (“junk DNA”) that does not code for protein. Although gene number can
be correlated with species complexity, there is no relationship between gene number, chromosome number, and total genome size.
To form a functional chromosome, a DNA molecule must be able to be replicated, and the replicated copies must be separated and
equally and reliably into the two daughter cells at each cell division. These processes occur through an ordered series of events, known
collectively as the cell cycle. Two broad stages of the cell cycle are the interphase, when chromosomes are duplicated, and the mitosis,
the much more brief stage when the duplicated chromosomes are distributed to the two daughter nuclei. During interphase,
chromosomes are extended as long, thin, tangled threads of DNA in the nucleus; “interphase chromosomes”. It is during interphase
that DNA replication takes place.
, Three specialized DNA sequences ensure that this process occurs efficiently:
۰ Replication origin; type of nucleotide sequence where DNA replication begins. Chromosomes contain
many replication origins to allow the long DNA molecules to be replicated rapidly.
۰ Telomere; type of nucleotide sequence that marks the end of a chromosome. It also serves as a
cap that keeps the chromosome tip from being mistaken by the cell as broken DNA.
۰ Centromere; type of nucleotide sequence that allows duplicated chromosomes to be separated
during M phase.
During the M phase of the cell cycle, the DNA coils up, ultimately forming highly compacted mitotic chromosomes.
The centromere allows the mitotic spindle to attach to each duplicated chromosome in a way that directs one copy
of each chromosome to be segregated to each of the two daughter cells.
Although interphase chromosomes are constantly undergoing dynamic rearrangements, each tends to
occupy a particular region of the interphase nucleus. Some chromosomal regions are physically
attached to particular sites on the nuclear envelope. This helps interphase chromosomes to remain
within their distinct territories. The most obvious example of chromosomal organization in the
interphase nucleus is the nucleolus. During interphase, the parts of different chromosomes that carry
genes encoding ribosomal RNAs come together to form the nucleolus. In the nucleolus, ribosomal RNAs
are synthesized and combine with proteins to form ribosomes, the cell’s protein-synthesizing machines.
This remarkable feat of compression is performed by proteins that coil and fold the DNA into higher and
higher levels of organization. These proteins are divided into two general classes:
۰ Histones; present in enormous quantities and as heavy as the DNA.
۰ Nonhistone proteins; present in large numbers and different kinds
The complex of both classes of protein with nuclear DNA is called chromatin. Eight histones (octamer)
with DNA wrapped around it is called a nucleosome. When it gets unfolded, it is visible as “beads on a
string” (without H1). The enzyme nuclease cuts the DNA by breaking the phosphodiester bonds between
nucleotides. When this nuclease digestion is carried out for a short time, only the exposed DNA between
the nucleosomes, “linker DNA”, will be cleaved, allowing the core particles to be isolated.
A nucleosome core particle consists eight histone proteins (two molecules each of histones H2A, H2B, H3,
and H4) and a segment of double-stranded DNA, 147 nucleotide pairs long, that winds around this
histone octamer. The linker DNA between each nucleosome core particle can vary in length from a few
nucleotide pairs up to about 80. All four of the histones that make up the octamer are relatively small
proteins with a high proportion of positively charged amino acids (lysine and arginine). The positive
charges help the histones bind tightly to the
negatively charged sugar–phosphate backbone of
DNA. Each of the histones in the octamer also has
a long, unstructured N-terminal amino acid “tail”
that extends out from the nucleosome core
particle. These histone tails can undergo
reversible, covalent chemical modifications that
control many aspects of chromatin structure.
The nucleosomes form a chromatin because of a
fifth histone (H1), which is thought to pull
neighbouring nucleosomes together into a regular repeating queue. H1 changes
the path the DNA takes as it exits the nucleosome core, allowing it to form a
more condensed chromatin fiber. Interphase chromosomes are formed by
specialized proteins that fold the chromatin into a series of loops, mitotic
chromosomes are formed by an extra level of packing.
