Higher Human Biology
Unit 1 Human Cells
1 Division and differentiation in human cells
(a) Following the formation of the zygote formed by the joining of the gametes the cells divide by
mitosis.
Cellular differentiation is the process by which a cell develops more specialised functions by
expressing the genes characteristic of that type of cell.
Cells may be grouped into stem cells, somatic cells and germline cells.
(b) Stem cells: These may be subdivided into embryonic and tissue (adult) stem cells.
 Stem cells are relatively unspecialised cells that can continue to divide and can differentiate
into specialised cells of one or more types.
 During embryological development the unspecialised cells of the early embryo differentiate
into cells with specialised functions.
 These include nervous tissue, muscle and the various types of blood cells.
 Embryonic stem cells can become any type of human cell – they are pluripotent.
 Tissue (adult) stem cells replenish differentiated cells that need to be replaced and give rise
to a more limited range of cell types – they are multipotent.
 Once a cell becomes differentiated it only expresses the genes that produce the proteins
characteristic for that type of cell, e.g. the genes for haemoglobin in a red blood cell.
The cells in bone marrow are tissue (adult) stem cells and are capable of differentiating into a variety
of different types of blood cell.
Some become red blood cells (erythrocytes), the genes for haemoglobin are expressed and the
nucleus eventually disintegrates. Others become platelets and are involved in blood clotting.
Phagocytes can be split into neutrophils, eosinophils, basophils and monocytes, according to their
function.
 Neutrophils defend against bacterial or fungal infection by phagocytosing
(engulfing and digesting) the invading microbes. They are the most numerous of
the white blood cells (60-70%) and are the main constituent of the pus in an
infected wound. They are short-lived.

Eosinophils are involved in causing inflammation in allergic reactions like
asthma and hay fever and in fighting parasitic infections.

Basophils release histamines causing vasodilation (widening of veins) as part
of the allergic response.

Monocytes present fragments of pathogens to the T cells to trigger
antibody production and also move out of the bloodstream into the
tissues where they undergo further differentiation into tissue
macrophages which carry out phagocytosis. Monocytes, unlike
neutrophils, are able to replace their lysosomal contents and live longer.
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Lymphocytes can be subdivided into B-lymphocytes, T-lymphocytes and natural killer cells according
to their function.
 B-Lymphocytes manufacture and release antibodies into the bloodstream
which then bind to pathogens, immobilising them.
 T-lymphocytes co-ordinate the immune response (helper T-cells) or bind to,
and kill virus-infected or tumour cells (cytotoxic T-cells). Suppressor T-cells
return immune system activity to normal after a bout of infection to prevent
autoimmunity.
 Natural killer cells also kill virus-infected or tumour cells.
(c) Somatic cells divide by mitosis to form more somatic cells.
 These differentiate to form different body tissue types: epithelial, connective, muscle and
nerve.
 The body organs are formed from a variety of these tissues.
 Epithelial cells cover the body surface and line body cavities, connective tissue includes
blood, bone and cartilage cells, muscle cells form muscle tissue and nerve cells form nervous
tissue.
 During cell division the nucleus of a somatic cell divides by mitosis to maintain the diploid
chromosome number.
 Diploid cells have 23 pairs of homologous chromosomes.
 Mutations in somatic cells are not passed to offspring.
(d) Germline cells divide by mitosis to produce more germline cells or by meiosis to produce
haploid gametes.
 Mutations in germline cells are passed to offspring.
(e) There is a great deal of research being carried out into the use of stem cells to repair diseased or
damaged organs or tissues, as disease models or for drug testing.
Stem cell research provides information on how cell processes such as cell growth, differentiation
and gene regulation work.
Stem cells have been used to grow skin for skin grafts used in
burns victims (http://www.bionews.org.uk/page_51463.asp),
for bone marrow transplants to cure leukaemia and to grow
replacement corneal tissue to repair damaged corneas and
restore sight.
(http://www.sciencedaily.com/releases/2012/03/120305160818
.htm).
As once source of stem cells is embryonic tissue their use can be controversial. Current UK law states
that embryo cells cannot be allowed to develop beyond 14 days (around the time an embryo would
implant into the uterus). The other sources of stem cells are tissues like muscle or differentiated cells
which have been reprogrammed back to a pluripotent state. Another technique used is nuclear
transfer where a nucleus is removed from a differentiated cell and placed in an egg cell which has
had its nucleus removed and is allowed to develop into a new organism. This was the technique used
to create “Dolly” the sheep, the first successful mammalian clone.
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Ethical concerns have led to regulations on the use of embryo stem cells, the use of induced
pluripotent stem cells and the use of nuclear transfer techniques.
(f) Cancer cells divide excessively to produce a mass of abnormal cells (a tumour) that do not
respond to regulatory signals and may fail to attach to each other.
If the cancer cells fail to attach to each other they can spread through the body to form
secondary tumours.
2 Structure and replication of DNA
(a) Structure of DNA
DNA is made of two strands of nucleotides held together by hydrogen
bonds between complementary bases on the nucleotides.
Each nucleotide consists of a deoxyribose sugar molecule joined to a
phosphate group and one of four nitrogen-containing “bases”, adenine,
thymine, guanine or cytosine.
The nucleotides join sugar to phosphate to sugar, etc, forming a sugarphosphate backbone.
All cells store their genetic information in the base sequence of DNA. The genotype is determined by
the sequence of DNA bases. DNA is the molecule of inheritance and can direct its own replication.
The bases pair in a particular way, adenine pairs with thymine
(A-T) and guanine pairs with cytosine (C-G). The base pairs are
held together by hydrogen bonds and the cumulative effect of all
the base pairs holds the two DNA strands together.
The two strands run in opposite directions, an antiparallel
arrangement.
Each strand finishes with a phosphate at
one (5’) end and the sugar at the other
(3’) end.
The two strands wind round one another
to form a double helix.
Chromosomes consist of tightly coiled
DNA and are packaged with associated
proteins.
Each cell requires a complete set of DNA so, prior to cell division, the DNA is replicated (copied)
using an enzyme called DNA polymerase. The replication process occurs at several locations on a
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DNA molecule. At these points one strand of the DNA molecule is cut and the DNA unwinds and
unzips, i.e. the strands separate. A short strand of complementary RNA nucleotides (a primer)
attaches to the exposed bases and further bases are added by DNA polymerase. Bases can only be
added to the 3’ (deoxyribose) end of the DNA strand so one side is replicated continuously and the
other is replicated in fragments which are joined by DNA ligase.
3 Gene expression.
(a) In any cell, only a fraction of the genes are expressed (translated into proteins). The phenotype
(physical appearance and function) of an organism is determined by the proteins produced as
the result of gene expression. Which genes are expressed is influenced by intra- and extracellular environmental factors. Gene expression is controlled by the regulation of both
transcription and translation.
(b) Structure and functions of RNA
RNA is formed by a string of nucleotides, similar to DNA, but the thymine in DNA is replaced by
another base, uracil, in RNA and the deoxyribose sugar is replaced by ribose. RNA is also single
stranded compared to the double stranded DNA. There are three types of RNA:
 Messenger RNA, or mRNA, carries a copy of the DNA code from the nucleus to the
ribosome.
 Ribosomal RNA, or rRNA, and proteins form the ribosome(s).
 Each transfer RNA, (tRNA), carries a specific amino acid.
(c) A mRNA molecule is transcribed
from DNA in the nucleus and
translated into proteins by
ribosomes in the cytoplasm. RNA
polymerase moves along DNA
unwinding and unzipping the
double helix and synthesising a
primary transcript of RNA by
complementary base pairing.
Genes have introns (non-coding
regions of genes) and exons (coding
regions of genes). The introns of the
primary transcript of RNA are removed.
The remaining exons are coding regions
and are then joined together to form
the mature transcript. This process is
called RNA splicing.
(d) Once transcribed, the mRNA is translated into a protein structure on a ribosome. Transfer RNA
molecules fold into a particular shape, forming a triplet anti-codon site and an attachment site
for a specific amino acid.
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The mRNA attached to the ribosome where there are two attachment
sites for tRNA molecules. A set of three bases (a codon) on the mRNA
determines which tRNA attaches by complementary base-pairing (A-U,
G-C, etc.) When two tRNA molecules are in place on the ribosome
their attached amino acids are joined by peptide bonds, the first tRNA
detaches from the ribosome, the second tRNA with the growing
polypeptide chain attached moves to position 1, a third tRNA with
another amino acid attached moves into position 2, joins to the
peptide chain, moves to position 1, etc until the whole mRNA
molecule has been translated into a polypeptide or until a stop codon
is reached.
There are specific “start” and “stop” codons on the mRNA which indicate where translation should
begin and terminate.
(e) Different mRNA molecules can be
produced from the same primary
transcript depending on which RNA
segments are treated as exons and
introns.
Once the polypeptide chain has been made
on the ribosome the chains can be cut to,
for example, form active enzymes, or
combined together (as in haemoglobin,
which has 2 α-chains and 2 β-chains). They
may also have carbohydrate or phosphate
groups attached. These post-translational
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modifications, combined with different RNA splicing, can result in more than one protein being
manufactured from the same gene, the one gene, many proteins concept.
4 Genes and proteins in health and disease
Proteins have a large variety of structures and shapes resulting in a wide range of functions. The
polypeptide chains fold to form a particular three dimensional shape held together by peptide
bonds, hydrogen bonds and other interactions between different amino acids.
Mutations, (alterations to the DNA), result in no protein, or a faulty protein, being produced.
Genetic disorders are caused by changes to genes or chromosomes that result in proteins not being
expressed or the proteins being expressed not functioning correctly.
Mutations can be classed as mutations within a single gene, gene mutations, where the DNA
nucleotide sequence is altered by substituting, inserting or deleting nucleotides.
Single nucleotide substitutions include missense (replacing one amino acid codon with another),
nonsense (replacing an amino acid codon with a premature stop codon — no amino acid is made
and the process stops) and splice-site mutations (creating or destroying the codons for exon-intron
splicing).
Nucleotide insertions or deletions result in frame-shift mutations or an expansion of a nucleotide
sequence repeat where all the amino acids after the insertion or deletion are altered.
Gene mutations tend to affect the structure and function of one particular protein which affects the
health of the individual affected.
Condition
Type of mutation
Sickle cell anaemia
missense
Phenylketonuria (PKU)
missense
Duchenne muscular dystrophy
nonsense
Tay-Sachs syndrome
frameshift insertion
Cystic fibrosis
frameshift deletion
Huntingdon’s disease
Fragile X syndrome
nucleotide sequence repeat
expansion.
nucleotide sequence repeat
expansion.
Effect on health
Malformed red blood cells,
impaired oxygen carrying
capacity.
Cannot metabolise phenyl
alanine – leads to mental
impairment.
Causes muscle wasting + early
death.
Deterioration of nerve cells,
early death (by 4 years old).
Impaired lung and digestive
function.
Affects muscle co-ordination +
cognitive function, early death.
Autism, ADHD, mental
retardation.
There are also larger scale mutations where the structure of a chromosome can be altered; these are
called chromosome mutations. These mutations can take the form of a deletion (loss of a segment
of a chromosome), duplication (repeat of a section of a chromosome) or translocation
(rearrangement of chromosomal material involving two or more chromosomes).
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The substantial changes in chromosome mutations often make them lethal.
Some examples of chromosome mutations are given below.
Condition
Cri-du-chat syndrome
Chronic myeloid leukaemia
Familial Down’s syndrome
Chromosome mutation
Deletion of part of short arm of chromosome 5.
Translocation of a gene from chromosome 22 fused with a
gene on chromosome 9.
Part of chromosome 21 translocated to chromosome 14.
5 Human genomics
Advances in analytical techniques and faster and cheaper computer processing has made it possible
to determine the sequence of DNA bases for individual genes and entire genomes (complete DNA of
an organism).
Bioinformatics is the use of computer technology to identify DNA sequences.
The enormous amount of data produced by DNA and protein sequencing can be managed and
analysed using computer technology and shared over the internet. Computer programs can be used
to identify gene sequences by looking for coding sequences similar to known genes, start sequences
or sequences lacking stop codons. Computer programs can be used to identify base sequences that
correspond to the amino acid sequence of a protein.
Systematics compares human genome sequence data and genomes of other species to provide
information on evolutionary relationships and origins.
Personalised medicine is based on an individual’s genome. Analysis of an individual’s genome may
lead to personalised medicine through understanding the genetic component of risk of disease. For
example, it may be that individuals carrying a particular allele of a gene have an increased risk of
developing a particular disease like breast cancer. The information gained from DNA studies can
provide information on the structure of the genes and proteins involved in disease. Rational drug
design synthesises specific drugs that will bind to these proteins or prevent their synthesis by
binding to a specific region of DNA preventing transcription or by binding to mRNA preventing
translation, for example interfering RNA (RNAi).
There are minor variations in DNA base sequence between individuals due to mutations; these may
be neutral, i.e. cause no ill-effects or harmful. Mutations in non-coding regions of DNA will be more
likely to be neutral than mutations in a region of DNA coding for a crucial gene. It may become
possible in the near future to tailor medicines to interact directly with DNA where the base sequence
in an individual is different from the majority of the population.
Polymerase chain reaction (PCR)
The polymerase chain reaction (PCR) is a technique for the amplification of DNA in vitro (in glass, i.e.
in a test tube). It is used to create large numbers of DNA molecules from a small original sample, a
process called amplification.
The DNA sample is heated to 95oC to separate the DNA strands; the strands are cooled (to 54oC)and
DNA primers added which bind to a specific target sequence of bases. A heat tolerant bacterial DNA
polymerase is then used to extend the DNA strands from the primers (at 72oC) until complete DNA
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molecules are obtained. The cycle is then repeated a number of times and the number of DNA
molecules obtained increases exponentially. This can be carried out automatically in a machine
which performs the necessary heating and cooling cycles and has a supply of nucleotides. The
amplified DNA can then be used for further analyses.
DNA probes are used to detect the presence of specific DNA bases sequences in a sample of DNA. A
DNA probe is a short single stranded fragment of DNA that is complementary to the specific
sequence of DNA being tested for. The probe will bind to the target sequence, if present, and can be
detected using a fluorescent label.
DNA probes can be used to detect single gene mutations
(single-locus probes) or to determine paternity. Multiple
probes can be used on a microarray to give a genotype
profile.
By screening a cell sample from a patient for the presence or
absence of a particular sequence, a diagnosis of disease
status or risk of disease onset can be made.
Each individual’s DNA has areas where there are repetitive sequences of nucleotide bases, e.g.
ATATATAT. The lengths of these sequences varies from person to person and are unique to the
individual. By digesting DNA samples with endonuclease enzymes and separating the fragments
using electrophoresis a DNA profile can be obtained as the DNA fragments will be different lengths
in different people due to the varying lengths of the repetitive sequences each individual’s DNA
profile is unique. The technique, called DNA fingerprinting, was developed by a British Scientist
called Alec Jeffreys and is now widely used around the world in criminal cases and to settle paternity
and immigration disputes.
6 Metabolic pathways
Metabolism encompasses the integrated and controlled pathways of enzyme catalysed reactions
within a cell.
Metabolic pathways involve biosynthetic processes (anabolism), e.g. the building of new proteins,
and the breakdown of molecules (catabolism) to provide energy and building blocks. Synthetic
pathways require the input of energy; pathways that break down molecules usually release energy.
Metabolic pathways may exist that can bypass steps in a pathway. These can sometimes cause the
creation and accumulation of unwanted metabolic products.
Metabolic pathways are controlled by the presence or absence of particular enzymes in the
metabolic pathway and through the regulation of the rate of reaction of key enzymes within the
pathway. Regulation can be controlled by intra- and extracellular signal molecules.
Genes for some enzymes are continuously expressed. These enzymes are always present in the cell
and their control involves regulation of their rate of reaction. These would include, for example, the
enzymes involved in the respiration pathways.
Most metabolic reactions are reversible and the presence of a substrate or the removal of a product
will drive a sequence of reactions in a particular direction. Some bacteria will produce an enzyme
which breaks down the sugar in milk, but only if exposed to the sugar. This ensures that the enzyme
is only made when needed, saving energy and resources.
The lock and key hypothesis of enzyme action did not really explain how the enzyme catalysed the
reaction and has been superseded by the induced fit hypothesis. In the induced fit hypothesis the
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enzyme and substrate still bind at the active site but there are particular amino acids at the active
site which have an affinity for the substrate, i.e. they attract by means of hydrogen and ionic bonds.
The attractive forces of these bonds ensure that the substrate(s) are orientated correctly, the
enzyme then closes around the substrate, the “induced fit”. Once held in this position the bonds in
the substrate are put under stress, making it easier for the desired reaction to occur, whether
anabolic or catabolic. By pushing together or pulling apart substrate molecules, the activation energy
(energy input needed for the reaction to occur) is lowered. Enzymes speed up reactions by holding
the reactants close together and by reducing the activation energy required for a reaction to occur.
The end products of the reaction have a lower affinity for the enzyme than the substrate and are
released from the active site.
The direction and speed of an enzyme reaction can be affected by the concentrations of the
substrate and end products. Increasing the substrate concentration will speed up a reaction as the
chances of the enzyme and substrate coming together are increased. The presence of high
concentrations of the end product can slow down or reverse a reaction. End products are normally
passed on to another reaction (where they become the substrate) and so do not normally
accumulate.
Enzymes often act in groups where the product of one reaction becomes the substrate for the next,
or as multi-enzyme complexes where a number of enzymes work together, as in DNA and RNA
polymerases.
Control of metabolic pathways can be achieved by competitive, non-competitive and feedback
inhibition.
Competitive inhibition occurs when the inhibiting substance has a similar shape and charge to the
substrate and competes with the substrate to bind to the active site. The effect of competitive
inhibition can be reduced by increasing the concentration of the substrate.
Non-competitive inhibition occurs when the inhibitor binds to another part of the enzyme, away
from the active site, changing the shape of the active site and preventing the substrate from binding.
Heavy metals, like lead, inhibit in this way.
Feedback inhibition occurs when the end product of a series of reactions binds to an enzyme that
catalyses a reaction early in the pathway, reducing that enzyme’s activity. This slows down the series
of reactions, preventing the production of more of the end product until its concentration falls and
the inhibition is removed.
7 Cellular respiration
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The metabolic pathways of cellular respiration are central to metabolism. They yield energy and are
connected to many other pathways.
ATP (Adenosine Tri-Phosphate) is used to transfer energy to synthetic pathways and other cellular
processes where energy is required.
At the beginning of the respiration pathway glucose is phosphorylated (has a phosphate group
added from ATP). This leads to a product that can continue to a number of pathways and a second
phosphorylation, catalysed by phosphofructokinase, is an irreversible reaction leading only to the
glycolytic pathway. This is regarded as an “investment” phase where ATP is consumed.
In the latter part of glycolysis ATP is generated, this is regarded as an energy pay-off phase. At the
end of the glycolysis stage pyruvate is formed which progresses to the citric acid cycle if oxygen is
available.
Pyruvate is broken down to an acetyl group that
combines with coenzyme A to be transferred to the
citric acid cycle as acetyl coenzyme A. Acetyl
coenzyme A combines with oxaloacetate to form
citrate followed by the enzyme mediated steps of
the cycle. This cycle results in the generation of ATP,
the release of carbon dioxide and the regeneration
of oxaloacetate in the matrix of the mitochondria.
Dehydrogenase enzymes remove hydrogen ions and
electrons which are passed to the coenzymes NAD or
FAD to form NADH or FADH2 in glycolysis and citric
acid pathways.
NADH and FADH2 release the high-energy electrons
to the electron transport chain on the mitochondrial
membrane and this results in the synthesis of ATP.
The electron transport chain is a collection of proteins attached to the folded inner membranes of
the mitochondria. NADH and FADH2 release the high-energy electrons to the electron transport
chain where they pass along the chain, releasing energy. The energy is used to pump H ions across
the inner mitochondrial membrane. The return flow of H ions rotates part of the membrane protein
ATP synthase and produces the bulk of the ATP generated by cellular respiration.
The final electron acceptor is oxygen, which combines with hydrogen ions and electrons to form
water.
Starch and glycogen are broken down to glucose for use as a respiratory substrate. Other sugar
molecules, e.g. fructose, can be converted to glucose or glycolysis intermediates for use as
respiratory substrates. Proteins can be broken down to amino acids and converted to intermediates
of glycolysis and the citric acid cycle for use as respiratory substrates. Fats can also be broken down
to intermediates of glycolysis and the citric acid cycle.
The cell conserves its resources by only producing ATP when required.
ATP supply increases with increasing rates of glycolysis and the citric acid cycle, and decreases when
these pathways slow down. If the cell produces more ATP than it needs, the ATP inhibits the action
of phosphofructokinase (PFK) slowing the rate of glycolysis. The rates of glycolysis and the citric acid
cycle are synchronised by the inhibition of phosphofructokinase by citrate. If citrate accumulates,
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glycolysis slows down and when citrate consumption increases glycolysis increases the supply of
acetyl groups to the citric acid cycle.
8 Energy systems in muscle cells
During strenuous muscle activity the cell rapidly breaks down its reserves of ATP to release energy.
Muscle cells have an additional source of energy in creatine phosphate that can be used to replenish
ATP pools during rigorous bouts of exercise. This system can only support strenuous muscle activity
for around 10 seconds, when the creatine phosphate supply runs out. When muscle energy demand
is low, ATP from cellular respiration is used to restore the levels of creatine phosphate.
During vigorous exercise, the muscle cells do not get sufficient oxygen to support the electron
transport chain. Under these conditions, pyruvate is converted to lactic acid. This conversion
involves the transfer of hydrogen from the NADH produced during glycolysis to pyruvic acid to
produce lactic acid. This regenerates the NAD needed to maintain ATP production through glycolysis.
Lactic acid accumulates in muscle causing fatigue. The oxygen debt is repaid when exercise is
complete; this allows respiration to provide the energy to convert lactic acid back to pyruvic acid and
glucose in the liver.
There are different types of skeletal muscle fibres:
Slow twitch (Type 1) muscle fibres contract more slowly, but can sustain contractions for longer and
so are good for endurance activities.
These muscle fibres are good for endurance activities like long distance running, cycling or crosscountry skiing. Slow twitch muscle fibres rely on aerobic respiration to generate ATP and have many
mitochondria, a large blood supply and a high concentration of the oxygen storing protein
myoglobin. The major storage fuel of slow twitch muscles fibres is fats.
Fast twitch (Type 2) muscle fibres contract more quickly, over short periods, so are good for bursts
of activity.
These muscle fibres are good for activities like sprinting or weightlifting. Fast twitch muscle fibres
can generate ATP through glycolysis only and have few mitochondria and a lower blood supply than
slow twitch muscle fibres. The major storage fuels of fast twitch muscles fibres are glycogen and
creatine phosphate.
Most human muscle tissue contains a mixture of both slow and fast twitch muscle fibres. Athletes
show distinct patterns of muscle fibres that reflect their sporting activities.