unit 3: cells, traits and cells of the nervous system Flashcards
synapse
basic input-output unit for transmission of information
macromolecules
organized to form the synapse, different types of macromolecules underlie the generation of impulse and other active properties involved in information processing
mendel’s observations
The genetic determinants are particulate; they don’t blend and they assort independently. He called the determinants elementen. Only much late was elementen called a gene
He concluded that each individual plant has two copies of elementen
Although all somatic cells have two copies of each allele, only one allele is passed on to an offspring from a female and one from a male in the form of a gamete in sexual reproduction
law of dominance
parents that are pure for contrasting traits, only one form of the trait will appear in the next generation
law of segregation
during the formation of gametes, the two alleles responsible for a trait separate from each other. alleles for a trait are then “recombined” at fertilization, producing the genotype for the traits of the offspring
allosteric proteins
many proteins change their shape upon binding a ligand
protein phosphorylation
post-translational modification of proteins in which certain amino acids in the chain of amino acids is phosphorylated by a protein kinase by the addition of a phosphate group allosteric proteins
- alters the shape of a protein, causing it to become activated, deactivate or modifying its function
dephosphorylation is catalyzed by
protein phosphatases
most commonly phosphorylated
serine, theonine, and tyrosine in eukaryotes
phosphorylation by ATP can activate an allosteric protein
Phosphorylation by ATP can activate an allosteric protein. In this example the inactive conformation of the non phosphorylated protein (A) is favored 1000 to 1 because of a free energy difference of 4.3 kcal/mole. When phosphorylated, the active conformation of the protein (B) is favored 100 to 1 (2.8 kcal/mole) because the phosphorylation produces an unfavorable charge repulsion, part of which is relieved by a shift to the active conformation C*. In this way phosphorylation “pushes” the enzyme into the active conformation. Alternatively, phosphorylation could create a charge attraction that brings together two separated parts of an allosteric protein.
generating mRNA from DNA
An enzyme (RNA polymerase) travels along DNA, making a messenger RNA (mRNA) transcript by adding nucleotides one at a time, copying the oligonucleotide sequence from one of the DNA strands. The strand of DNA used as the template for the RNA strand is called the sense strand. RNA is made only from one of the two DNA strands. The strand that is not transcribed into mRNA is called the antisense strand.
base pairing and hybridization
- Hybridization is the process of combining two complementary single-stranded DNA or RNA molecules and allowing them to form a single double-stranded molecule through base pairing. In a reversal of this process, a double-stranded DNA (or RNA, or DNA/RNA) molecule can be heated to break the base pairing and separate the two strands. Hybridization is a part of many important laboratory techniques such as polymerase chain reaction (PCR) and Southern blotting.
the process of generating a peptide from mRNA
The nucleotides in an mRNA molecule are joined together to form a complementary copy of a segment of one strand of DNA. They are then matched three at a time to complementary sets of three nucleotides in the anticodon regions of transfer RNA (tRNA) molecules. At the other end of each type of tRNA molecule, a specific amino acid is held in a high-energy linkage, and when matching occurs, this amino acid is added to the end of the growing polypeptide chain. Thus, translation of the mRNA nucleotide sequence into an amino acid sequence depends on complementary base-pairing between codons in the mRNA and corresponding tRNA anticodons. The molecular basis of information transfer in translation is therefore very similar to that in DNA replication and transcription. Note that the mRNA is both synthesized and translated starting from its 5’ end.
The genetic code consists of sequences of three bases (codons) that are laid out along a strand of mRNA.
Another form of RNA, transfer RNA (tRNA), carries specific amino acids to their “docking sites” so that the amino acids are in close proximity to one another.
An enzyme causes the formation of a peptide bond and the new amino acid is attached to its predecessor.
a series of ribosomes simultaneously translate the same RNA molecule
Ribosomes are the organelles in the cytoplasm on which mRNA is translated into proteins. Ribosomes themselves are RNA molecules (i.e., ribosomal RNA; rRNA). For each polypeptide chain being synthesized from an mRNA molecule in a eukaryotic cell, protein synthesis begins with the binding of a small ribosomal subunit to the single appropriate site on the mRNA molecule and proceeds from the 5’ end to the 3’ end of the mRNA chain. When a polypeptide chain is completed, the two ribosomal subunits dissociate from the mRNA.
protein synthesis
The nuclear envelope keeps functional ribosomes out of the nucleus, so that RNA transcripts can be extensively processed (spliced) before they are transported out of the nucleus into the cytoplasm, where they are translated into proteins by ribosomes. Thus, RNA processing and transport steps are interposed between DNA transcription and RNA translation.
This figure shows the movement of mRNA out of the nucleus, into the cytoplasm, the attachment of ribosomes, and finally the attachment of the ribosomes to the endoplasmic reticulum (ER) where, in this particular case, the protein is made.
This figure also illustrates how a protein formed in the rough ER moves through the smooth ER to the Golgi apparatus where the protein is “packaged” in granules.
In the case of neurons, these secretory granules may contain neurotransmitters or enzymes involved in transmitter synthesis.
The transmitter or transmitter enzyme is transported down the axon to the nerve termina
phenylketonuria
If undetected and untreated, PKU leads to a profound intellectual disability.
Affects 1 in 5,000 newborns in Western Europe
Autosomal recessive trait
The heterozygous trait is rather common (2%).
Therefore, 2 heterozygous parents have a 1 in 4 chance of having a child with PKU.
PKU can be detected at birth (Guthrie Test).
Treatment is feeding a diet low in phenylalanine and rich in tyrosine.
Phenylalanine hydroxylase gene (PKU) mapped on human chromosome 12q24.1
Phenylalanine accumulates in the blood because of a block in conversion to tyrosine (lack of phenylalanine hydroxylase).
conversion of phenylalanine to tyrosine
The chemical structures and co-factors can be disregarded. However, the reaction of conversion of phenylalanine to tyrosine by phenylalanine hydroxylase is the first step in the synthesis of catecholamines (dopamine, norepinephrine, and epinephrine), a metabolic cascade with which you should be eventually familiar.
thomas hunt morgan
- columbia university
- founder of modern experimental genetics
- chromosomal theory of hereditary
- drosophila melanogaster
- 1933 nobel prize
archibald garrod
british physician
- 1909 recognized that the disease alkaptonuria was caused by a rare recessive gene mutation inherited according to mendelian rules
- “inborn errors of metabolism” surmised the nature of the genetic defect
- “we may further conceive that the splitting of the benzene ring in normal metabolism is the work a special enzyme, that in congenital alkaptonuria this enzyme is wanting”
alkaptonuria
was caused by a recessive gene mutation inherited according to mendelian rules
- characterized by the accumulation of homogentisic acid in the body. affected individuals lack enough functional levels of an enzyme required to breakdown homegentisic acid
george w beadle
1958 nobel prize
- neurospora crassa (bread mold)
- normal spores require only water, sugar, ammonium salt, and biotin
- 1 in 1000 required an enriched medium of a single added substance such as a vitamin or amino acid to restore growth
- they concluded that the mutant cells carried a defect in a single gene that impaired the production of an enzyme for a single metabolic step
- that is: one gene was responsible for one enzyme
functional roles of peptides/proteins
- enzyme system
- signaling (first and second messengers)
- structural
- motility
- transport and storage
- immune system functions
- regulation of transcription
- nutrition
activation in absence and presence of a catalyst
- biochemical reactions require energy to occur
- enzymes reduce the amount of energy for a given reaction to take place
- therefore, the availability of enzyme determines the amount of product made by a given cell
allosteric proteins
many proteins change their shape upon binding a ligand
protein phosphorylation
a post-translational modification of proteins in which certain amino acids in the chain of amino acids is phosphorylated by protein kinase by teh addition of a phosphate group
the reverse reaction of phosphorylation
dephosphorylation and is catalyzed by protein phosphatases
protein kinases and phosphatases
work independently and in balance to regulate the function of proteins
most commonly phosphorylated are
serine, threonine, and tyrosine in eukaryotes
phosphorylation by ATP can activate an allosteric protein
can activate an allosteric protein. In this example the inactive conformation of the non phosphorylated protein (A) is favored 1000 to 1 because of a free energy difference of 4.3 kcal/mole. When phosphorylated, the active conformation of the protein (B) is favored 100 to 1 (2.8 kcal/mole) because the phosphorylation produces an unfavorable charge repulsion, part of which is relieved by a shift to the active conformation C*. In this way phosphorylation “pushes” the enzyme into the active conformation. Alternatively, phosphorylation could create a charge attraction that brings together two separated parts of an allosteric protein.
DNA to RNA to protein
The transfer of information from DNA to protein occurs by means of an RNA intermediate called messenger RNA (mRNA). The process of producing mRNA from DNA is called transcription and the process of constructing proteins from an mRNA template is called translation. In eucaryotes the coding regions of the DNA (in the exons) are separated by noncoding regions (called introns). As indicated, these introns must be removed by an enzymatically catalyzed RNA splicing reaction to form the mRNA.
M phase
cell division phase of the cell cycle starts at the end of G2 phase and ends at the start of the next G1 phase. it includes the five stages of nuclear division (mitosis) and cytoplasmic division (cytokinesis)
generating mRNA from DNA
an enzyme (rna polymerase) travels along DNA, making a messengeer RNA (mRNA) transcript by adding nucleotides one at a time, copying the oligonucleotide sequence from one of the DNA strands. the strand of DNA used as the template for the RNA strand is called the sense strang. RNA is made only form one of the two DNA strands. the strand that is not transcribed into mRNA and is called the antisense strand
base pairing and hybridzation
hybridization is the process of combining two complementary single-stranded DNA or RNA molecules and allowing them to form a single double-stranded molecule through base pairing
generating a peptide from mRNA
The nucleotides in an mRNA molecule are joined together to form a complementary copy of a segment of one strand of DNA. They are then matched three at a time to complementary sets of three nucleotides in the anticodon regions of transfer RNA (tRNA) molecules. At the other end of each type of tRNA molecule, a specific amino acid is held in a high-energy linkage, and when matching occurs, this amino acid is added to the end of the growing polypeptide chain. Thus, translation of the mRNA nucleotide sequence into an amino acid sequence depends on complementary base-pairing between codons in the mRNA and corresponding tRNA anticodons. The molecular basis of information transfer in translation is therefore very similar to that in DNA replication and transcription. Note that the mRNA is both synthesized and translated starting from its 5’ end.
The genetic code consists of sequences of three bases (codons) that are laid out along a strand of mRNA.
Another form of RNA, transfer RNA (tRNA), carries specific amino acids to their “docking sites” so that the amino acids are in close proximity to one another.
An enzyme causes the formation of a peptide bond and the new amino acid is attached to its predecessor.
generating a peptide from mRNA
The nucleotides in an mRNA molecule are joined together to form a complementary copy of a segment of one strand of DNA. They are then matched three at a time to complementary sets of three nucleotides in the anticodon regions of transfer RNA (tRNA) molecules. At the other end of each type of tRNA molecule, a specific amino acid is held in a high-energy linkage, and when matching occurs, this amino acid is added to the end of the growing polypeptide chain. Thus, translation of the mRNA nucleotide sequence into an amino acid sequence depends on complementary base-pairing between codons in the mRNA and corresponding tRNA anticodons. The molecular basis of information transfer in translation is therefore very similar to that in DNA replication and transcription. Note that the mRNA is both synthesized and translated starting from its 5’ end.
The genetic code consists of sequences of three bases (codons) that are laid out along a strand of mRNA.
Another form of RNA, transfer RNA (tRNA), carries specific amino acids to their “docking sites” so that the amino acids are in close proximity to one another.
An enzyme causes the formation of a peptide bond and the new amino acid is attached to its predecessor.
a series of ribosomes simultaneously translate the same RNA molecule
Ribosomes are the organelles in the cytoplasm on which mRNA is translated into proteins. Ribosomes themselves are RNA molecules (i.e., ribosomal RNA; rRNA). For each polypeptide chain being synthesized from an mRNA molecule in a eukaryotic cell, protein synthesis begins with the binding of a small ribosomal subunit to the single appropriate site on the mRNA molecule and proceeds from the 5’ end to the 3’ end of the mRNA chain. When a polypeptide chain is completed, the two ribosomal subunits dissociate from the mRNA.
protein synthesis
The nuclear envelope keeps functional ribosomes out of the nucleus, so that RNA transcripts can be extensively processed (spliced) before they are transported out of the nucleus into the cytoplasm, where they are translated into proteins by ribosomes. Thus, RNA processing and transport steps are interposed between DNA transcription and RNA translation.
This figure shows the movement of mRNA out of the nucleus, into the cytoplasm, the attachment of ribosomes, and finally the attachment of the ribosomes to the endoplasmic reticulum (ER) where, in this particular case, the protein is made.
This figure also illustrates how a protein formed in the rough ER moves through the smooth ER to the Golgi apparatus where the protein is “packaged” in granules.
In the case of neurons, these secretory granules may contain neurotransmitters or enzymes involved in transmitter synthesis.
The transmitter or transmitter enzyme is transported down the axon to the nerve terminal.
examples of human genetic defects
sickle cell anemia and phenylketonuria, caused by a single mutation and follow the medelian rules of inheritance
phenylketonuria
An example of a “simple” inborn error of metabolism
- If undetected and untreated, PKU leads to a profound intellectual disability.
- Affects 1 in 5,000 newborns in Western Europe
- Autosomal recessive trait
- The heterozygous trait is rather common (2%).
- Therefore, 2 heterozygous parents have a 1 in 4 chance of having a child with PKU.
- PKU can be detected at birth (Guthrie Test).
- Treatment is feeding a diet low in phenylalanine and rich in tyrosine.
- Phenylalanine hydroxylase gene (PKU) mapped on human chromosome 12q24.1
- Phenylalanine accumulates in the blood because of a block in conversion to tyrosine (lack of phenylalanine hydroxylase).
conversion of phenylalanine to tyrosine
The chemical structures and co-factors can be disregarded. However, the reaction of conversion of phenylalanine to tyrosine by phenylalanine hydroxylase is the first step in the synthesis of catecholamines (dopamine, norepinephrine, and epinephrine), a metabolic cascade with which you should be eventually familiar.
francis galton
Hypothesized that intellectual abilities must follow the rules of inheritance in the same way as the physical traits of height and eye color.
Heredity Genius (published in 1889).
Coined the term “eugenics”
First to use the experimental approach of twin studies.
genome wide association studies
help identify alleles of genes associated with a particular trait. This method studies the entire set of DNA (the genome) of a large group of people, searching for small variations, called single nucleotide polymorphisms or SNPs
missing heritability
Extensive research over the past two decades on many traits that are determined by multiple genes find that adding up the contribution of each of the individuals QTLs associated with the identified trait will not account for the known heritability associated with that phenotype
Hypertension is a highly heritable disorder (30 to 40% of the variability) of multi genetic complexity
However, adding all the contributions from “hypertensive genes” accounts for only a very small increase in blood pressure
epigenetics
is the study of heritable changes in gene activity that are not caused by changes in the DNA sequence
The term epigenetics was coined by the developmental biologist C.H Wassington in 1942. He introduced the concept as a model to consider of how genes might interact with their surroundings to produce a phenotype
Can be used to describe anything other than alterations in the DNA sequences that influences the development of an organisms and phenotype of an individual
pharmacogentics
describes the interactions between drug and individuals characteristics
- based on observations of clinical efficacy and/or the safety and tolerability profile of a drug in individuals
-based on the concept that interindividual differences in an observed drug response may be associated with the presence or absence of individual-specific molecular markers that may allow a prediction of a given individual’s response to a drug.
Such biological markers are most commonly polymorphisms at the level of the nuclear DNA, but conceivably also other types of nucleic acid-derived data, such as quantitative gene expression measurements, or epigenetic changes which serve as surrogates for DNA expression.
unipolar cells
have a single process, are characteristic of the invertebrate nervous system.
-In invertebrates, different segments of a single axon serve as receptive surfaces or releasing terminals.
bipolar cells
have two processes: the dendrite, which carries information toward the cell, and the axon, which transmits information away from the cell. Neurons in the dorsal root ganglia of the spinal cord (B), which carry sensory information to the central nervous system, belong to a subclass of bipolar cells called pseudo-unipolar. As such cells develop, the two processes of the embryonic bipolar cell become fused and emerge from the cell body as a single process. This process then splits into two processes, both of which function as axons, one going peripherally to skin or muscle, the other going centrally to the spinal cord.
multipolar cells
which have an axon and many dendritic processes, are the most common type of neuron in the mammalian nervous system. Three examples show the large diversity of shape and organization. The spinal motor neuron innervates skeletal muscle fibers. The pyramidal cell has a pyramid shaped cell body. Dendrites emerge from both the apex (the apical dendrite) and base (the basal dendrites). Pyramidal cells are found in the hippocampus and throughout the cerebral cortex. The Purkinje cell of the cerebellum is characterized by its rich and extensive dendritic tree in one plane. This structure is designed to accommodate an enormous synaptic input.
types of glia
astrocytes, oligodendroglia, microglia, radial glia
functions of flia
Structure
Diffusion barrier
Insulation - oligodendroglia and schwann cells
Facilities message conduction
Takes up ions (K+) and certain molecules
Source of biologically active molecules
Phagocytosis
Neural development
Immune functions
formation of myelin
During development, a process of an oligodendrocyte or an entire Schwann cell tightly wraps itself many times around an individual axon and forms one segment of the myelin sheath. (a) Oligodendrocyte. (b) Schwann cell.
processes of the glia
-very long, extending from the inner surface to the outer surface of the developing neural tube and its derivative structures. The arrows indicate that the cells migrate along the processes from the inner surface of the cerebral hemisphere to the marginal zone at the outer surface.
- From the close relation between the processes of the migrating neuron and the radial glial cell, it is clear that the migrating neuron depends on the glial substrate for guidance.
microglia
- macrophages
- cells of the immune system that have migrated into the CNS
- they patrol the CNS, attacking infectious agents and removing debris
- exist in activated and inactivated states
- sources of biochemicals called cytokines that promote inflammation
