Target Qs Flashcards
What is the active form of vitamin D?
1,25 - dihydroxycholecalciferol / Calcitriol
Explain how hypercalcemia occurs as a result of vitamin D toxicity
- Vitamin D is important for calcium homeostasis in our body
- Normally, it increases calcium absorption from the intestine
- Increases calcium reabsorption from the kidney
- Deposits calcium and phosphate in the bones
- Regulates the PTH levels and prevents excessive bone resorption
- Vitamin D toxicity often occurs due to over supplementation
- Causes osteoclastic bone resorption other than bone mineralization
- } Serum calcium level is elevated and is known as hypercalcemia
- Causes various symptoms such as muscle weakness, cardiac arrhythmias, calcification of organs etc.
Factors that affect iron absorption in the gut
- Phytates
- Tea
- Ca2+
- Mg2+
Describe the regulation of iron in the body
- Regulated at absorption level
- Hepcidin is a protein synthesized by the liver
- Hepcidin can bind with ferroprotein which is responsible for transporting iron from mucosal cells to circulation
- Hepcidin degenerates ferroprotein and causes reduce in iron absorption
- If there is low iron, hepcidin synthesis is inhibited and causes increase in iron absorption
- High iron level leads to increase in hepcidin level thus causing reduce in iron absorption
- Iron is stored in mucosal cells as ferroproteins
- If there are adequate iron stores in mucosal cells, iron loss occurs when cells are desquamated
Regulatory step for fatty acid synthesis
Explain why fatty acid synthesis is active in fed state while fatty acid breakdown is active in fasting state
Fed state:
1. Insulin/glucagon ratio rises
2. Causes dephosphorylation and activation of acetyl CoA carboxylase which is the rate limiting enzyme of FA synthesis
3. Activation of FA synthesis produces more and more malonyl CoA which has an inhibitory effect on CPT-1
4. } FA breakdown is reduced
5. Insulin also inhibits HSL by dephosphorylation
6. Causes reduce in amount of FFA available for beta oxidation
Fasting state:
1. Glucagon causes cAMP mediated phosphorylation of acetyl CoA carboxylase
2. Inhibits the enzyme and leads to reduced FA synthesis
3. } Malonyl CoA production is also reduced
4. Inhibitory effect on CPT-1 is now released and allows FA to enter into mitochondria for beta oxidation
5. Glucagon also phosphorylates HSL and activates it
6. More and more triglyceride breakdown occurs, causing more FAs available for beta oxidation
Describe how acetyl CoA enters ketogenesis during starvation
- During starvation FA oxidation increases
- FA oxidation produces acetyl CoA, NADH, FADH2
- Increase in NADH favors the conversion of OAA to malate which can then exit from mitochondria and be converted back to OAA in the cytosol
- This OAA can then be used for gluconeogenesis
- NADH is an inhibitor of citrate synthase enzyme which can produce citrate from OAA and acetyl CoA
- High NADH produced by↑ FA oxidation inhibits this enzyme
- Causes acetyl CoA to accumulate in the liver
- Excess acetyl CoA is then metabolized by alternative pathway known as ketogenesis
List the enzymes that catalyze the irreversible steps of glycolysis
- Hexokinase
- PFK-1
- Pyruvate kinase
List the enzymes that catalyze the irreversible steps of gluconeogenesis
- Glucose-6-phosphatase
- Fructose-2,6-bisphosphate
- Pyruvate carboxylase & PEP carboxykinase
Outline the steps involved in the entry of glycerol into gluconeogenesis
Explain the biochemical basis for using statins to maintain hypercholesterolemia
- Condition characterized by high levels of cholesterol in the blood
- Acetyl CoA is converted to cholesterol by sets of reactions
- HMG CoA → mevalonate by HMG CoA reductase enzyme (rate limiting enzyme of this synthetic pathway)
- Inhibiting this enzyme can reduce the cholesterol level in the body
- Statins are drugs which have similar chemical properties as HMG CoA
- } Statins can competitively inhibit HMG CoA reductase
- Statins are used to treat hypercholesterolemia
List 3 post-transcriptional modifications and explain their importance
- 5’ capping → prevents degeneration of mRNA & helps to form initiation complex of translation
- Polyadenylation → prevents from degeneration
- Splicing and ligation → removes non-coding introns from pre-mRNA
Explain how alternative splicing increases the functional capacity of the genome
- Process by which a single gene can give rise to multiple different mRNA and therefore different proteins
- Achieved by creating different combinations of exons during splicing and ligation of pre-mRNA
- Allows a single gene to produce multiple protein isoforms
- Can expand the proteome without additional genes
- Different protein isoforms can have distinct functions enabling cells to adapt to various physical or environmental stresses
- Alternative splicing enables different tissues or developmental stages to produce proteins best suited to their needs from the same gene
- } Alternative splicing increases the functional capacity of the genome
Explain the biochemical basis of vitamin C deficiency
- Collagen is a key, structural protein in the body, which provides strength and support for various tissues
- Essential for the integrity and strength of connective tissues
- Collagen is synthesized as alpha chains + alpha chains form triple helical structure to form mature collagen
- Triple helical structure of collagen is mainly stabilized by hydrogen bonds
- Hydroxylation of proline and lysine residues increases the formation of hydrogen bonds
- Vitamin C is a co-factor of the enzymes responsible for this hydroxylation process
- If vitamin C is deficient, hydroxylation + hydrogen bond formation between alpha chains is reduced
- Causes production of weak collagen molecules
- Leads to more fragile blood vessels that bleed more easily contributing to gum bleeding & subcutaneous hemorrhage
