Things I need to go over before Exam 2 (WEEK 2 material)

Sigma factor is at the _______ point in DNA. Pridnow Box is at the ______ point in DNA

-35 and -10

In eukaryotes, how does initiation begin for transcription?

Initiation of transcription in eukaryotes begins when transcription factors bind to the promoter region (TATA, GC or CAAT), TFIIB binds to promoter, TFIIE and TFIIB are recruited to site. and TFIIH unwinds DNA with helicase activity. TFIIH also activates the RNA polymerase via phosphorylation.

How is termination done in Eukaryotes for transcription?

Termination in eukaryotes involves the recognition of specific sequences in the RNA transcript, such as the polyadenylation signal, which triggers the addition of a poly-A tail and the cleavage of the pre-mRNA, eventually leading to RNA polymerase dissociating from the DNA.

Splicing mutation in the Acceptor site of an Intron

makes the mRNA shorter

Splicing mutation that introduces an acceptor site

makes mRNA longer (retaining some of the intron)

Splicing mutation in Donor site of the intron

makes mRNA longer

Describe the G1 phase of the cell cycle.

In G1, the cell size increases, protein synthesis is active, differentiation occurs, and the cell performs its functions. At the end of G1, the cell checks whether it is ready for division.

What is the G0 phase? Definition: The G0 phase is a quiescent phase where cells can perform functions but are unable to divide. Permanent and stable cells reside in G0, while stable cells can reenter the cell cycle in the presence of stimuli, such as growth factors.

Explain the S phase of the cell cycle.

During the S phase, DNA synthesis and replication occur. The enzymes of replication are active, and the DNA proofreading activity of RNA polymerase is active. Each chromosome replicates, and at the end of S phase, the DNA content doubles, resulting in each chromosome having two sister chromatids.

What happens during the G2 phase?

In the G2 phase, the DNA content is double, the cell and cytosol size increase, and the genome is scanned for mistakes. Post-replication DNA repair mechanisms are active.

List the stages of the M phase.

M phase includes Prophase, Metaphase, Anaphase, and Telophase.

G1/S checkpoint

The G1/S checkpoint is a critical regulatory point in the cell cycle where a cell assesses whether it is ready to enter the S phase. Factors such as cell size, nutrient availability, and DNA integrity are evaluated, ensuring that only healthy cells proceed to DNA replication.

G2/M checkpoint

the stage in the cell cycle where the cell verifies that DNA replication has been completed accurately and checks for DNA damage before proceeding to mitosis.

M check point

also known as the spindle checkpoint, ensures that all chromosomes are properly aligned and attached to the spindle apparatus before the cell proceeds to anaphase during mitosis.

What check point is p53 at?

The G1/S checkpoint, where it helps monitor DNA damage and can halt the cell cycle for repairs.

Describe Prophase during the M phase.

In Prophase, the nuclear envelope dissolves, the mitotic spindle forms, chromosomes condense and become visible, and they bind to the spindle.

What happens during Metaphase?

In Metaphase, chromosomes condense and are maximally visible, aligning at the equator, visualized by karyotyping, and microtubules attach to the centromere kinetochores.

Explain Anaphase.

In Anaphase, sister chromatids move to the centrioles; this is the separation of sister chromatids. Non-disjunction during Anaphase is known as mitotic non-disjunction.

Describe Telophase and its significance.

In Telophase, sister chromatids move to opposite poles, the nuclear envelope starts forming, chromosomes become less condensed, and two new daughter cells are formed from cytokinesis, which have the same genetic composition as the parent cell.

Non Disjunction I

is the failure of homologous chromosomes to separate properly during meiosis I, resulting in gametes with an abnormal number of chromosomes, which can lead to conditions (47 XXY = Klinefelter syndrome) (1 add in)

Non disjunction II

A failure of homologous chromosomes or sister chromatids to separate properly during meiosis II, leading to gametes with an abnormal number of chromosomes; XXX syndromes

Metacentric

p and q arms are of same length; centromere is in center of chromosome

Submetacentric

p arm is shorter than q arm

Acrocentric

p arm contains little genetic information; involved in Robertsonian translocation (satellite structure)                          

Telocentric

having the centromere terminally situated so that there is only one chromosomal arm

Catecholamine synthesis is in the

adrenal medulla

Tertiary structure

description of the location of all atoms in a protein in space due to amino acid side-chain interactions. This includes domains which are the functional 3D structural units of polypeptides

Quaternary structure

describes the composition of a protein that consists of two or more polypeptide chains

Alpha-helix:

1.     The spiral has 3.6 residues per turn

2.     Hydrogen bonds are parallel to the direction of the imaginary axis and are formed between peptide bonds

3.     The side chains project to the outside of the cylinder

4.     Proline or glycine residues often terminate the alpha-helix

5.     The alpha helix is interrupted by electrostatic repulsion/attraction between charged amino acid side chains or due to steric hindrance by bulky side chains

Beta-pleated sheet

hydrogen bonds between the peptide bonds stabilize the beta-pleated sheet which is formed by two or more peptide chains. Amino acid side chains alternate above and below the plane of the pleated sheet. The protein strands can be anti-parallel or parallel. The beta-turn involves four successive amino acid residues and permit change of direction of the peptide chain

Heteroplasmy

the presence of two or more distinct types of mitochondrial DNA within a cell or organism, which can lead to variable expression of mitochondrial diseases.

heterozygosity

the presence of two different alleles at a gene locus in a diploid organism, contributing to genetic diversity.

homozygosity

the presence of two identical alleles at a gene locus in a diploid organism, leading to reduced genetic diversity.

allelic heterogeniety

the phenomenon where different alleles at the same gene locus can cause the same phenotype or trait, often seen in genetic disorders.

locus heterogeneity

different spot/ same disorder.

homoplasmy

the condition of having identical mitochondrial DNA sequences in all copies of the mitochondrial genome within a cell or organism.

Coenzymes

are enzymes that have incorporated vitamins and minerals

Apoenzymes

enzymes without the coenzyme

Noncompetitive

increased Vmax, no change in Km; binds at allosteric site

Competitive Inhibition

binds at active site; increases Km, no change in Vmax.

Suicide Inhibition

A type of irreversible enzyme inhibition where the inhibitor binds to the active site and is converted into a reactive form that permanently inactivates the enzyme. Example is Allopurinol

Irreversible Inhibition

What is an example of an Irreversible inhibitor?

Aspirin (inhibits cyclooxygenase enzymes or COX)— Adds ‘acetyl’ group to Serine at active site. DFP - Organophosphate insecticides (DFP) irreversibly inhibit

acetylcholinesterase

What is DFP?

an irreversible inhibitor of acetylcholinesterase; Acetylcholinesterase cleaves the neurotransmitter acetylcholine in the postsynaptic neuromuscular junction. DFP leads to accumulation of acetylcholine with devastating results. Continuous stimulation of muscle contraction and overstimulation of the autonomic nervous system leads to blurred vision, bronchoconstriction, seizures, respiratory arrest, and death

DIFP forms covalent bond with

Serine residue in active site

In platelets, COX forms

Thromboxane A2 (TXA2) from arachidonic acid → facilitates

platelet aggregation and clot formation

In endothelial cells, COX forms

Prostacyclin (PGI2) → inhibits platelet aggregation

What does thromboxane (TXA2) do?

it increases platelet aggregation which increases clots

What does Prostacyclin (PGI2) do?

It inhibits platelet aggregation

Allopurinol

treatment for gout; inhibits Xanthine oxidase (Purine nucleotide degradation)

what brings the charged tRNA to the p site of the ribosome (eukaryotes)

IF-2

GTP is hydrolyzed on IF-2 and IFs are relased when

the 50s subunit arrives to form the 70s complex

Catechalomines are made from

tyrosine

What is the steps to make epinephrine/Norepinephrine

Tyrosine→L Dopa→ Dopamine→ NE or Epinephrine

What is the intermediate that will accumulate if there is a mutation in catecholamine?

dopamine

Denaturation involves

changing the configuration of a shape

Peptide bonds are resistat to what?

conditions that denature proteins such as heat and high concentrations of urea.

A helices have nboth

van der waals and hydrogen bonding

what amino acid disrupts alpha helices

proline

myoglobin structure is

tertiary globular protein; single chain (153 AA) plus a prothetic group; 8 alpha-helical regions; exterior is polar hydrophilic; interior is non polar hydrophobic

Where is myoglobin located and what does it do?

Myoglobin is primarily found in muscle tissue, where it serves to store and transport oxygen to muscle cells.

Structure of hemoglobin

contains 2 alpha nd 2 beta subunits; these form a 2 aB dimers;

Dimers are held together by

hydrophobic interactions, stabilizing the overall protein structure.

What holds Hemoglobin together?

4 polypeptide chains held together by weak ionic and hydrogen bonds

Abnormal proteolytic cleavage of amyloid precursor protein

Alzheimer's disease.

The amyloid precursor protein allows for the spontaneous formation of a fibrilar protein aggregated called

beta-ameloid plaques

Ameyloid fibrils

neurotoxic and cause cognitive impairment

hyperphosphorylated tau protein

accumulation of neurofibrillary tangles

Prion disease

a group of neurodegenerative disorders caused by misfolded proteins that lead to brain damage and are infectious.

in normal prion disease, what does it have the most of?

alpha helices

in infectious prion disease, what does it have the most of?

beta-sheets