Cell Biology Flashcards
Site of RNA splicing ??
Nucleus
Pre-messenger RNA (m-RNA) ==> Mature mRNA
- Introns are removed & Exons (protein coding part) are joined
Give some eg. of diseases caused by Splicing errors
Famial Parkinson’s (Chr 17)
Fronto-Temporal Dementia
What pharmacokinetic property is a/w highest level of clearance by Dialysis ??
- High water solubility (drugs are removed by Counter-Current Flow across Semi-permeable memb.
- Compound should be in Plasma at high conc.
- Low protein bound compound
- Molecular size < 10 kDa
What does drug with high lipid solubility indicate ??
High lipid solubility => Increased Tissue binding
In which part of the cell is Insulin receptor is located ??
Cell membrane (a Transmemb. receptor)
- It is a Tyrosine Kinase receptor
Give eg. of a Cytoplasmic receptor
Androgen receptor
Hallmark of Nuclear receptor ??
These regulate Gene expression
- eg.- Peroxisome proliferator-activated receptors, Retinoids & Vit. D receptors
What is the primary function of microRNAs ??
Silencing of mRNA
- microRNAs target particular segments of mRNA to silence them, preventing ribosomal binding to mRNA & protein translation
How is gene transcription regulated ??
by Repressors & Activators
- Repressor binds to the operator region on DNA => impedes RNA polymerase progress on DNA
- Activators increase the attraction of RNA polymerase for a promoter region of DNA, increasing Transcriptional activity
How is mitochondrial func. regulated ??
- Nutritional status (fasting & Glucagon production stimulation improves Mitochondrial’s energy production
- PPAR-Alpha & PPAR-Gamma activity
How is protein degradation regulated ??
- Recognition by Ubiquitin molecules & subsequent digestion by 26S proteosome
What is Protein Phosphorylation ??
- Driven by KINASES
- MC & important Post-translational modifications; in this, Phosphate groups are added to the polar group R of various amino acids, which can lead to gain/loss of function by inducing a conformational change in protein structure
What is the function of Peroxisome ??
Oxidation of Very Long-Chain FAs to liberate energy
What is Refsum’s disease ??
- A R
- Impaired Beta oxidation of VLC FAs
- Causes build up of Phytanic acid & its derivatives in plasma & tissues
- Progressive visual loss, impaired night vision due to R pigmentosa
Which HIV peptide plays a role in initial step for HIV entry into cells ??
GP-41
- GP 120 fuses to the CD4 receptor, which then allows GP-41 to penetrate the cell memb.
Features of Vit B12 ??
aka Cobalamin; Essential water-soluble vit.
Source: Meat, fish, eggs & dairy
Produced by certain Bacteria in the gut
How is Cobalamin absorbed, transported in the body ??
- Binds to [IF] produced in the stomach => forms a complex => absorbed in the SI
- Once absorbed, Vit.B12 binds to Transcobalamin II (TC II) for transport in the blood stream
- TC II - B12 complex delivers B12 to cells
- Enters cells through Receptor-mediated Endocytosis
What happens to Vit B12 inside the cells ??
After entering the cell, B12 undergoes conversion to its active coenzyme forms- Methylcobalamin & Adenosylcobalamin
- M Cobalamin: participates in Methionine synthesis (key step in DNA synthesis)
- A Cobalamin: needed for conversion of Methylmalonyl-CoA ==> Succinyl-CoA (a process of Energy metabolism)
Role of B12 in
- DNA synthesis ??
- Energy metabolism ??
- M Cobalamin donates ‘Methyl’ grp. for conversion of Homocysteine ==> Methionine- needed for DNA methylation
- A Cobalamin facilitates breakdown of certain Fatty A & Amino A
- It is a cofactor for enzyme Methylmalonyl-CoA mutase, prevents the accumulation of toxic metabolites
What is the main pathology of the following
- Methylmalonic Acidemia (MMA) ??
- Homocystinuria ??
- Build up of Methylmalonic acid due to impaired B12 function
- Elevated levels of Homocysteine due to impaired B12 metabolism
What are the active forms of B12 (Cobalamin) ??
Methyl-B12 & Adenosyl-B12
Features of Folate ??
Vit. B9, a water soluble vitamin
Sources: Leafy green, legumes, fruits & fortified grains
Essential for normal growth & devt., specially during pregnancy
How is B9 absorbed, & processed intracellularly ??
- Absorbed in Jejunum; converted to its active forms- Dihydrofolate & Tetrahydrofolate
- Active forms are utilized in 1-carbon transfer reactions, critical for syn. of Nucleotides, Amino A & other cellular components
- DHF-reductase converts DHF ===> THF; a crucial step in regeneration of active folate forms
What is the use of Folate in
- DNA synthesis ??
- Amino Acid synthesis ??
- Methylation reaction ??
Significance of Folate Metabolism ??
Megaloblastic anaemia
Neural tube defect
Elevated Homocysteine levels, a/w Folate deficiency, may contribute to CVS disease
Which drug does the following to Folate
- Interfere with metabolism ??
- Reduce absorption ??
- Trimethoprim, MTX, Pyrimethamine
- Phenytoin
Manifestations of Vit. C deficiency ??
Scurvy: leads to defective synthesis of collagen resulting in capillary fragility (bleeding tendency) & poor wound healing
Features
- Gingivitis, Loose teeth
- Poor wound healing
- Bleeding from gums, Haematuria, Epistaxis
- General malaise
What are the functions of Vit. C ??
Water soluble vitamin
- Antioxidant
- Collagen synthesis: acts as a co-factor for enzymes that are required for hydroxylation of Proline & Lysine in collagen synthesis
- Co-factor of Norepinephrine synthesis
What is sources of Ascorbic acid ??
Source: Citrus fruits, Tomatoes, potatoes, Brussel sprouts, cauliflower, broccoli, cabbage & spinach
What is Scurvy ??
Vit C deficiency => impaired Collagen synthesis & disordered connective tissue as it is a cofactor for enzymes used in Proline & Lysine production => Capillary fragility => Bleeding tendency
- Follicular Hyperkeratosis & Perifollicular Haemorrhage
- Ecchymosis, easy bruising
- Poor wound healing
- Gingivitis, bleeding & receding gums
- Sjogren’s. - Arthralgia. - Oedema.
- Impaired wound healing
- Generalized weakness, malaise, anorexia & depression
What is Vit. D and their sources ??
Fat soluble vitamin that plays key role in Ca2+ & PO4- metabolism
- Vit D ==Liver==> Calcifediol (prohormone) aka Cholecalcidol ==Kidney==> CALCITRIOL (Vit D active form)
Source:
- D2 (Ergocalciferol): Plants
- D3 (Cholecalciferol): Dairy products, can be synthesized by SKIN under sunlight
Features of vit D deficiency ??
RICKETS : in Children
OSTEOMALACIA : in Adults
What is Vit. D resistant rickets ??
X-linked Dominant condition; presents in Infancy with FTThrive
- Due to IMPAIRED PO4- Reabsorption in renal tubules
C/F-
- FTT
- Normal Ca2+, Low PO4-, High ALP
- X-ray: Cupped Metaphyses + Widening of Epiphyses
How to Dx. & Rx of Vit. D Resistant Rickets ??
By demonstrating HIGH Urinary PO4-
Rx.-
- High dose Vit. D supplements
- Oral PO4- supplements
Features of Vit. K ??
Fat soluble vitamin which acts as a cofactor in Carboxylation of Clotting Factors (2, 7, 9, 10)
- Used to reverse Warfarinization
- Takes >= 4hrs to see a change in INR
Deficiency
- Seen in conditions affecting Fat absorption
- Due to prolonged use of Broad-spectrum Abx. by killing Gut flora
What are the indications for Nutritional support ??
- BMI < 18.5
- 10% body wt. loss unintentionally in the past 3 to 6 months
- BMI < 20 + > 5% unintentional wt. loss in the past 3 to 6 months
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What is DIC ??
Simultaneous Coagulation & Haemorrhage caused by the initial formation of thrombi => consumes clotting factors (5, 8) & platelets => leading to Bleeding
- Bleeding is a dominant feature, bruising, ischaemia & organ failure
Blood profile of DIC ??
Prolonged Clotting times
Thrombocytopenia
Decreased Fibrinogen
Increased F degradation product
What are the metabolism products of Arachidonic acid ??
Phospholipids ==Phospholipase A2===> Arachidonic acid- produces 2 substrates
- AA ==COX1,COX2==> Endoperoxides
- AA ==(Lipooxygenase)==> HPETSs ==> LB4 & Leukotrienes
What are produced by Endoperoxidase matabolism ??
Prostacyclin (PGI2)
- Vasodilation
- Decreases Plt. aggregation
- Decrease Uterine tone
Prostaglandin (PGE2)
- Increase Pain, Temp., Uterine tone, Gastric mucosa
THROMBOXANES (TXA2)
- Vasoconstriction
- Increases Plt. aggregation
What are the functions of LB4 & Leukotrienes ??
Both are the products of HPETEs metabolism
LTB4: Increases Neutrophil Chemotaxis
Leukotrienes:
- A4, C4, D4 & E4: ALL constricts lungs (Bronchoconstriction)
