How Nucleic Acids Go From Here To There

1. How Nucleic Acids Go From Here To There By: Laura Capparilli, Tyler Horton, Zach Johnston, and Kim Hagey

2. DNA • Characteristics of DNA: double-stranded, double helix, antiparallel • Nucleic Acid: polymeric macromolecules made from nucleotide monomers • Nucleotide: An organic molecule that serves as a monomer of nucleic acid • Nucleoside: any various compound of sugar paired with either a purine or pyrimidine

3. RNA • Characteristics: • single-stranded • Uracil replaces Thymine

4. Bases: Purines and Pyrimidines • Purine: A nitrogen-containing substance derived from uric acid • Purine bases: Adenine and Guanine • Pyrimidine: A nitrogenous base with a six-sided structure • Pyrimidine bases: Cytosine, Thymine, Uracil • Base Paring in DNA: A=T, C=G • Base Pairing in RNA: A=U, C=G • Main functions: • 1. DNA/RNA Replication • Short Term energy storage of ATP

5. Breakdown in GI • Mouth – Mastication & Deglutition Esophagus- movement of bolus via peristalsis through LES Stomach- Nucleic Acids dissolve in gastric chyme

6. Digestion in the Small Intestine Chyme enters the duodenum, and the pancreas releases pancreatic juice which contain: Ribonuclease - breaks down RNA into ribonucleotides Deoxyribonuclease - breaks down DNA into deoxyribonucleotides

7. Digestion in the Small Intestine

8. BrushBorder Further digestion occurs at the microvilli in the S.I. from two enzymes: Phosphatases & Nucleosidases

9. Products of Digestion • So your final products are Phosphate ion, pentose sugars, and a nitrogenous base. • Duodenum and Jejunum absorb the products in the epithelial cells.

10. Absorption • Membrane transport proteins carry the products to the simple columnar using active and secondary transport.

11. Absorption • Diffusion of the products from the simple columnar epithelium across the basolateral membrane into the interstitial fluid, into the capillary. • Where the Pyrimidines and Purine bases undergo De-Novo Synthesis, the pathway, and Salvage Pathway

12. De-novo Synthesis • Why? Nucleic acids may not be readily available • De-novo synthesis is the creation of complex molecules from simpler molecules like sugars or amino acids • De-novo synthesis also refers to the process of DNA replication • For example, primase is an RNA polymerase and it can add a primer to an existing strand. DNA polymerase cannot and therefore needs to add the primer, de-novo • The de-novo pathway does not use free bases (A,G,C,T,U)

13. De-novo Pathway • The purine ring is built up one atom or a few atoms at a time and attached to ribose throughout the process • The pyrimidine ring is synthesized as orotate (heterocyclic compound) and attached to ribose phosphate • The ribose phosphate is converted into common pyrimidine nucleotides • The enzymes involved in De-novo synthesis are present as large multienzyme complexes, such as folate, carbon dioxide, and glutamine.

14. Salvage Pathway • Bases and nucleosides are formed during degradations of RNA & DNA • The SALVAGE PATHWAYis used to recover these molecules • This is especially important in tissues that cannot undergo De Novo Synthesis

15. Salvage Pathway

16. Human Urate Homeostasis • Urate is produced as the major end product of purine metabolism by liver, muscles, and intestine. • The biosynthesis of urate is catalyzed by xanthine oxidase (XO). • Approximately two thirds of the daily turnover of urate is accounted for by urinary excretion, with the remaining one third being excreted into the gut as feces.

17. Purine Degredation Guanine and Adenine are converted to Uric Acid

18. Products of pathway • Nuclease frees the nucleotide • Nucleotidase frees guanosine • Guanosine is converted to guanine • Guanine converted to xanthine • Xanthine converted to uric acid

19. Hyperuricemia • An abnormally high level of uric acid in the blood. • High levels of uric acid in the blood can lead to gout, which is a medical condition characterized by recurrent attacks of acute inflammatory arthritis.

20. Gout

21. Valsalva Maneuver • Forceful attempted expulsion of air with plugged nose and closed mouth • Clears pressure in the middle ear

22. Valsalva Maneuver • 4 stages: • Initial Pressure Rise • Reduced Venous Return and Compensation • Pressure Release • Return of Cardiac Output

23. Valsalva Maneuver

24. Valsalva Maneuver • Can help diagnose: • Cardiovascular issues • Neurological issues • Urogenital Problems

25. Valsalva Maneuver • Clinically, the Valsalva Maneuver is done against a closed glottis • This is a common sensation when exerting force such as lifting a heavy object or trying to force defecation

26. Defecation Reflex • Defecation is the final act of digestion by which organisms eliminate solid, semisolid, or liquid waste from the GI tract via the anus

27. Defecation Reflex • The rectum ampulla (dilated section of the rectum where feces is stored until it is expelled) acts as a temporary fecal reservoir • As rectal walls stretch due to filling, stretch receptors stimulate the desire to defecate • This causes contraction of rectal muscles, relaxation of the anal sphincter, and contraction of the external anal sphincter

28. Defecation Reflex • If not acted upon, fecal matter returns to the colon via reverse peristalsis • Water is reabsorbed from fecal matter in the colon • If defecation is prolonged for too long, constipation can occur • If defecation occurs too quickly, diarrhea will occur

29. Defecation Reflex • Defecation is normally assisted by taking a deep breath and trying to expel this air against a closed glottis • The Valsalva Maneuver aids in creating pressure in the chest such that the thorax exerts pressure on the digestive tract in the abdomen

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