MCBD test 1

How does purine affect metabolism

excess purine can cause hyperuricemia and cause uric acid crystals to deposit in the joins and lead to inflammation and gouty arthritis

how does pyrimidine affect metabolism

defect in synthesis leads to impaired nucleic acid synthesis which is necessary for hematopoiesis and elads to megaloblastic anemia. (bone marrow produces large RBC’s)

what is central dogma?

DNA, RNA, proteins

Explain replication of the lagging strand

Here's the sequence on the lagging strand:

1. Helicase unwinds the DNA, exposing the template strand.

2. Primase lays down a short RNA primer complementary to the template.

3. DNA polymerase attaches to the primer and adds DNA nucleotides in the 5′ → 3′ direction, forming an Okazaki fragment.

4. Primase lays down another RNA primer farther along the newly exposed template.

5. DNA polymerase makes another Okazaki fragment.

6. The RNA primers are removed and replaced with DNA, and DNA ligase joins the fragments.

Explain steps of replication

1. Helicase unzips the DNA

2. RNA primer gets placed down

3. DNA poly synthesizes DNA

4. Topoisomerase makes nicks to prevent super coil and rejoins DNA fragments

What is the function of DNA polymerase III

1. Allow RNA primers to bind and add nucleotides and synthesize a new strand of DNA

2. Also proofreads

Function of RNA primer

Starting point for replication

Function of DNA poly I

Remove rna primers and replace with DNA

Function of ligase

Links DNA fragments together

DNA primase

Puts RNA primers on the DNA

Helicase inhibitors

Pritelivir & Amenamevir: prevents helicase from unzipping DNA

• inhibitors of viral helicase

• effective against herpes simplex virus

Topoisomerase inhibitor

1. blocks the ligation step (rejoining of the fragments)

2. results in large amounts of fragmented DNA

3. cell destabilized

4. cell death

Drugs that are topoisomerase inhibitors

Quinolones (levofloxacin, ciprofloxacin)

• for skin and tissue infections

Anti cancer agents (camptothecines)

DNA polymerase inhibitor

Acyclovir: effective against herpes, shingles by inhibiting DNA synthesis

What is a telomere and what is hayflicks limit

• Telomeres are a single stranded overhand not copied during replication

• hayflicks limit is the amount of times a cell can divide before the telomere gets too short and inflicks cell death or cellular senescencet

What is telomerase

• extends the telomeres

• active in germ cells but not as much in somatic cells

• cancer cells reactive telomerase for immortality

Telomerase dysfunction

Dykeratosis congenita:

• white patches, brittle nails, squamous cell cancers, premature tooth loss

• biological disorder that causes telomere shortening faster than expected and leads to cell senescence

• fast dividing cells at risk: hair, skin, nails

• cancer risk due to short telomere cells going into apoptosis or senescence but if they mutate and get past biological defense then you have rapid mutated cells dividing

What causes DNA damage

UV light, radiation, chemicals

What are the 4 ways DNA can repair itself

Direct reversal, base excision repair, nucleotide excision repair, non-homologous end joining

What is direct reversal

alkylation damage reversed when alkyl group transferred

• methyl group adds onto a nucleotide and MGMT comes in and removes it and attaches methyl group onto itself so then the base is not chemically altered and can go find its match

• fixes base

What is base excision repair

DNA damage is cleaved by endo/exonuclease and correct base pairs inserted. for example cytosine becomes uracil in deamination and so the mutated base gets cut out

• cuts out bad base

Nucleotide excision repair

cuts out a stretch of nucleotide damage from uv radiation and repairs the bases

What is non-homologous end joining

Double strand breaks joined back together, do not need a sister chromatid. Usually needs to trim or fill in a few nucleotides

Lynch syndrome

genetic disorder where DNA places wrong base pair, fails to correct mismatch repair and continues to replicate with mutation and leads to risk of colon cancer and endometrial cancer.

Xeroderma pigmentosum

defective nucleotide excision repair

• cannot repair DNA damage

• hypersentivity to UV: leads to mutations since they cannot be cut out

• tumors of the lips, tongue, buccal mucosa

• 3-4 years old starts to show signs

Defects on lips and tongue

lip: squamous cell carcinoma

tongue: varicose carcinoma

Explain transcription

initiation: RNa poly binds to promoter and unwinds the DNA

• no primers

elongation: RNA poly moves from 3’ to 5’ and produces the DNA transcription by adding nucleotides to the 3’ end of the growing RNA

termination: rna poly reaches terminations ite and rns transcript is sent free to go to cytosol. T —> U

Explain post transcriptional modification

in nucelous and converts pre mRNA to mature mRNA

• 5’ capping, splicing out introns, and poly A tail

Steps in translation

1. 
   

• Initiation: Small ribosomal subunit binds mRNA and recognizes the AUG start codon.

• Initiator tRNA binds: Brings methionine (Met) and binds directly to the P site.

• Ribosome assembly: Large ribosomal subunit joins.

• Elongation: Next tRNA enters the A site, bringing the next amino acid.

• Peptide bond formation: Amino acids are joined to extend the polypeptide chain.

• Translocation: Ribosome moves along mRNA 5′ → 3′; tRNAs shift through the A, P, and E sites.

• Termination: Ribosome reaches a stop codon (UAA, UAG, or UGA); a release factor releases the completed polypeptide.

what are microRNAs and long noncoding RNAs

• they do not code for proteins

• both regulate gene expression in development of cancer

• microRNAs are small and cause translational repression and mRNA degradation (reduce gene expression)

• long noncoding RNAs: long group of nucleotides and control gene expression in various ways

Alternative splicing

Splices out the introns, can make various different proteins from the same gene

• 20,000 genes can make 100,000 different proteins

Examples: IgM vs. IgG during early vs late viral infections

• membrane bound Ig vs secreted Ig

• muscle proteins tropomyosin vs. troponin T

List and describe the five cardinal signs of inflammation

• Rubor: redness

• Dolor: pain

• Calor: heat

• Tumor: swelling

• Function Laesa: loss of function

What is acute inflammation

• Starts with response of blood vessels, early and immediate response to injury

Triple response of lewis:

• vasoconstriction: white at first (does this to prevent blood loss if bleeding)

• vasodilation: blood flow increases and slows down, blood cells accumulate at area

• Edema: endothelial cells contract and plasma fluid starts to move into damaged area

Transudate

edema fluid with los protein content. Occurs in non-inflammatory conditions. Endothelial barrier intact and prevent loss of large molecules

Exudate

Fluid with high protein concentration that contains inflammatory cells. Observed in acute inflammatory reactions

• serous: watery low molecular weight (blister)

• sanguinous: contains blood (blood blister)

• fibrinous: high MW due to activation of the coagulation system. severe injury (pericarditis)

• purulent or suppurtative: contains inflammatory cells and dead cells (pus and bacterial infections)

Abscess

local collection of pus

Sinus

track leading from an abscess to a skin or mucous surface

Fistula

track leading from a mucous surface to the skin or to another mucous surface

Neutrophils

PMNs: multiple segmentations in the nucleus. most numerous inflammatory cells, most important, arrive first

Platelets

regulate vascular permeability, coagulation, and proliferation response of connective tissue cells

Endothelial cells

• line blood vessels

• release substances that promote coagulation

• express cell adhesion molecules to leukocytes can line periphery of BV

• regulate vasoconstriction and dilationSte

Steps of endothelial activation

1. activation: activate inflammatory mediators (histamine, thrombin, PAF, TNF, IL-1)

2. margination: inflamm cells move to the periphery of the blood vessel as blood flow slows

3. rolling/tethering: theya ttach to the endothelial cells and start rolling along the blood vessel wall

4. adhesion: adhere to the endothelial cells

5. emigration: squeeze between the endothelial cells and chemotaxis takes them to the site of injury

acute inflammation leads to

resolution, abscess, or scar

Chronic inflammation leads to

regeneration or scar

What is chronic inflammation

active inflammation, tissue injury, and healing proceed all together

can be caused by immune diseases, chronic infection, cancer, repeated trauma

Characteristics of chronic inflammation

1. infiltration with monoculcear leukocytes: monocytes, plasma cells, and lymphocytes

2. tissue destruction

3. repair: proliferation of blood vessel and fibrosis

Cells of acute inflammation

platelets and neutrophils

Cells of chronic inflammation

eosinophils, basophils - mast cells, monocytes - macrophages, lymphocytes - plasma cells

macrophages

• play a role in acute

• key role in chronic

• regulate inflammatory and immune response as well as coagulation

• migrate within 24-48 hrs as monocytes then go to macrophages and do phagocytosis

• acute: leave after job is done

• chronic: stay, linger and persist and proliferate

lymphocytes

B and T cells, look identical under microscope,

T cells: activated when macrophages present antigen

Plasma cells

differentiated B cells, produce antibodies against antigens. clock faces nucleus and more abundant cytoplasm with paler zone

Eosinophils

parasitic infections, granules, mediated by IgE and modulate mast cell mediated reactions.

Mast Cells

Armed with IgE that was produced by plasma cells. degranulate and release histamine. Regulate vascular permeability. release inflamm mediators histamine and serotonin. Cell surface receptors for IgE.

• work with eosinophils

Granulomatous inflammation

• type of chronic inflamm with large numbers of macrophages that wall off infection to other surfaces

• somtimes a central zone that exhibits necrosis

• an inner cellular zone of macrophages and langhan giant cells

• outer cellular rim of other chronic inflamm cells (plasma, lymphocytes, and immature macrophages)

How to tell type of granuloma

Specific type of necrosis in center that is due to the cause of the granuloma

Acute phase response

physiological reaction that occurs in inflamm conditions

• fever, decreased appetite, changes in c-reactive protein

Fever

release of pyrogens from bacteria or viruses

• chills, rigor, sweats