!!FOOD!! Podcast --- Ghrelin (Radio show + transcript) & Hormone Class I

Hey guys, here is the link to my podcast on Ghrelin. :) Below is the transcript. ENJOY! :)

  Welcome to the show! Thank you for tuning in Flash in the Pan, and I’m your host Linfei. For today’s episode, we will be talking about why we are always hungry?! Have you ever felt like; umm I want to eat something. Despite you just had a delicious meal, and you were full five minutes ago, our stomachs keep on growling and telling us: FOOD!! We want more! Well, this is because Ghrelin is stimulating the brain and giving rise to an increase in appetite. Ghrelin is the reason why we love food so much and we can’t help but eat more. So, what is this foodie, Ghrelin? Ghrelin is a water-soluble, 28-amino acid hunger stimulating peptide and hormone that is responsible for not only the stimulation in the brain (in order to increase in appetite), but also the accumulation of lipids in visceral fatty tissue. According to the National Digestive Diseases Clearing House, Ghrelin is produced in the stomach and upper intestine in the absence of food in the digestive system. It is produced mainly by P/D1 cells lining the fundus of the human stomachs and epsilon cells of the pancreas that stimulates appetite. Ghrelin is also produced in the hypothalamic arcuate nucleus, where it stimulates the secretion of growth hormone from the anterior pituitary gland. Also, Receptors for ghrelin are expressed by neurons in the arcuate nucleus and the lateral hypothalamus. The ghrelin receptor is a G protein-coupled receptor, formerly known as the GHS receptor (growth hormone secretagogue receptor). 

  On the other hand, Ghrelin can also be secreted by the lungs, pancreatic islets, gonads, adrenal cortex, placenta, kidney, and brain. The diversity in areas of ghrelin production indicates that this hormone has various and numerous biological functions, such as gastrointestinal tract, learning and memory, anxiety response and depression, sleep duration, appetite inducer, chronic stress and PTSD and body weight regulation. So, how does ghrelin work?

  Ghrelin has a negative feedback loop that ghrelin is involved in regulating our bodies. As the body loses weight, ghrelin levels rise in response to the energy deficit. Studies had researched this topic through fasting, but an experiment had not yet been run. Studies found that ghrelin levels increased in response to modest weight loss resulting from exercise without a reduction in food intake. Thus, ghrelin also plays a role in the body’s adaptive response to weight loss, either through reducing food intake or increasing levels of physical activity. Ghrelin and synthetic ghrelin mimetic (the growth hormone secretagogues) increase food intake and increase fat mass by an action exerted at the level of the hypothalamus. They activate cells in the arcuate nucleus that include the orexigenic neuropeptide Y (NPY) neurons. Ghrelin also activates the mesolimbic cholinergic-dopaminergic reward link, a circuit that communicates the hedonic and reinforcing aspects of natural rewards, such as food.

  Do not underestimate ghrelin! It is not just a foodie. It is also a harm/threat to our health. As mentioned before, ghrelin also favors the accumulation of lipids in visceral fatty tissue. This type of accumulated fat in the region of the abdomen that is deemed to be most harmful, as it is accompanied by comorbilities. Also, visceral obesity is related to the risk of getting higher blood pressure or type II diabetes. Moreover, being located in the abdominal zone and in direct contact with the liver, this type of fatty tissue favours the formation of liver fat and increases the risk of developing resistance to insulin. Nevertheless, there are ways to regulate ghrelin from releasing. Factors could affect ghrelin levels are nutrient stimulation of the gastrointestinal tract, diet composition and weight loss. Moreover, as all hormones work on a feed back loop, something triggers its release and something stops it from being released. Therefore, another hormone that is found to be secreted from the stomach in response to food ingestion could moderate ghrelin levels. This hormone is peptide P YY3-36. It can blunt ghrelin secretions; thus, it creates lower appetite and reduces food intake. Leptin could regulate ghrelin as well. Leptin is a 16-kDa adipokine that plays a vital role in regulating energy intake and expenditure, including appetite and hunger, metabolism and behavior. It is one of the most important adipose-derived hormones. Leptin functions by binding to the Leptin receptor (LEP-R), and it is located on chromosome 7 in humans. Besides hormone, scientists have developed an anti-obesity vaccine to regulate ghrelin. The vaccine uses the immune system, specifically antibodies, to bind to selected targets, directing the body's own immune response against them. This prevents ghrelin from reaching the central nervous system, thus producing a desired reduction in weight gain.

Best way to control weight and stay healthy is to eat slowly and to wait twenty minutes to let the body signal to you that you are full. That’s all for today! Thank you for listening, and remember to give your stomach a twenty-minute-break! See you next time!

Three types of Chemical Pathway 

Leptin's sturcture

Ghrelin's sturcture

This is how Ghrelin works! 

Ghrelin action to stimulate GH secretion

Regulation 

Watch out Ghrelin!! 

Work Cited:
1. Alvarez-Castro, P., et al. “Marked GH Secretion after Ghrelin Alone or Combined with GH Releasing Hormone (GHRH) in Obese Patients.” Clinical Endocrinology, 61 (2), 2004. 250-255. Retrieved from: http://www.userwebs.pomona.edu/~ejc14747/student%20presentations/McKibben_Ghrelin.pdf

2. Basque Research. (2009, May 26). Action Of Ghrelin Hormone Increases Appetite And Favors Accumulation Of Abdominal Fat. ScienceDaily. Retrieved February 24, 2014 from www.sciencedaily.com/releases/2009/05/090520055519.htm

3. Kojima, Masayasu, and Kenji Kangawa. “Ghrelin: Structure and Function.” Physiological Reviews, 85 (2), 2005. 495-522. Retrieved from: http://www.userwebs.pomona.edu/~ejc14747/student%20presentations/McKibben_Ghrelin.pdf

4. Williams, D. L., & Cummings, D. E. (2005). Regulation of ghrelin in physiologic and pathophysiologic states. Informally published manuscript, The American Society for Nutritional Sciences, Retrieved from http://nutrition.highwire.org/content/135/5/1320.full

5. Wren, A.M., et al. “Ghrelin Enhances Appetite and Increases Food Intake in Humans.” Journal of Clinical Endocrinology and Metabolism, 86 (12), 2001. Retrieved from: http://www.userwebs.pomona.edu/~ejc14747/student%20presentations/McKibben_Ghrelin.pdf

6. http://www.news-medical.net/health/Ghrelin-What-is-Ghrelin.aspx

7. http://www.healthaliciousness.com/blog/The-Hormones-of-Digestion.php

*Colored parts are in the actual audio 

Cell Respiration

Cellular respiration allows organisms to use (release) energy stored in the chemical bonds of glucose.  The energy in glucose is used to produce ATP. Cells use ATP to supply their energy needs. Cellular respiration is therefore a process in which the energy in glucose is transferred to ATP.

In respiration, glucose is oxidized and thus releases energy. Oxygen is reduced to form water.

The carbon atoms of the sugar molecule are released as carbon dioxide (CO2).
The complete breakdown of glucose to carbon dioxide and water requires two major steps: 

1) glycolysis and 2) aerobic respiration. Glycolysis produces two ATP. Thirty-four more ATP are produced by aerobic pathways if oxygen is present.
In the absence of oxygen, fermentation reactions produce alcohol or lactic acid but no additional ATP.

Electron carriers: 

NAD+ + 2H --> NADH + H+
FAD + 2H --> FADH2

I. Glycolysis:

During glycolysis, glucose (C6) is broken down to two molecules of pyruvate (C3).

Glycolysis occurs in the cytoplasm (cytosol) and does not require oxygen.

1) 2 ATP molecules are used to phosphorylate and activate compounds that will eventually become converted to pyruvate (or pyruvic acid).

2) Two hydrogen atoms are removed by NAD+ forming 2 NADH.

3) Additional phosphorylation results in intermediate 3-carbon molecules with 2 phosphate groups.

4) 4 ATP are produced by substrate-level phosphorylation. Recall that substrate-level phosphorylation is the production of ATP using energy from other high-energy compounds but without the use of the electron transport system in the mitochondria.

And the net yield of ATP in glycolysis is 2 for each glucose molecule (2 are used but 4 are produced).

II. Formation of Acetyl CoA(Coenzyme A) 
Pyruvate produced by glycolysis enters the mitochondrion by active transport and is converted to acetyl CoA as shown below. The remainder of the reactions of cellular respiration occur in the mitochondrion.

pyruvate (C3) --> acetyl CoA (C2) + CO2

A carbon atom is removed from each of the pyruvate molecules forming a two-carbon compound and CO2. Each of the two-carbon compounds are oxidized forming NADH from NAD+.  Coenzyme A is attached to each of the two-carbon compounds producing two acetyl CoA molecules.

III. Krebs Cycle 

The Krebs Cycle is the central metabolic pathway in all aerobic organisms. The cycle is a series of eight reactions that occur in the mitochondrion. These reactions take a two carbon molecule (acetate) and completely oxidize it to carbon dioxide. The cycle is summarized in the following chemical equation:

acetyl CoA + 3 NAD + FAD + ADP + HPO₄^-2 ------> 2 CO₂ + CoA + 3 NADH⁺ + FADH⁺ + ATP

The Krebs Cycle is an aerobic process (one that requires oxygen) that produces ATP by breaking down glucose. The Krebs Cycle is not only part of the pathway for the breakdown of glucose, but also for the breakdown of all metabolites, including other sugars, amino acids and fatty acids. Each of these groups of molecules has a pathway that leads into the Krebs Cycle. 

Steps in the Krebs Cycle:

1. The first reaction in the Krebs Cycle is the conversion of pyruvate to acetyl CoA. In this reaction, pyruvate, a three carbon molecule that is generated in glycolysis and in the metablism of some amino acids, is decarboxylated (a carboxyl group is removed) to the two carbon acetate. The carboxyl group is released as carbon dioxide. This reaction is catalyzed by the enzyme pyruvate dehydrogenase. This reaction is also an oxidation as 2 electrons are removed from pyruvate during the reaction. The two electrons are accepted by NAD and results in the formation of NADH. The oxidation of pyruvate is very exogonic. Some of the energy released from this reaction is transferred with the electrons to NADH and some is used to energize acetate by adding coenzyme A to acetate thus forming acetyl CoA, the actual product of the reaction.

substrates(reactants )	pyruvate	CoA + NAD
enzyme	pyruvate dehydrogenase
products	acetyl CoA	CO2 + NADH

2. This reaction is a condensation reaction (a reaction that joins together two molecules) in which the 2-carbon acetate that was formed from pyruvate in the preceding reaction is attached to a 4-carbon molecule, oxaloacetate (OAA). The reaction creates the 6-carbon molecule (2 carbons from acetate and 4 from OAA) citrate. The joining of the acetate to OAA requires energy and this energy comes from the removal of the coenzyme A from the acetate.

substrates(reactants )	acetyl CoA + oxaloacetate
enzyme	citrate synthase
products	citrate (citric acid)	+ Co A

3. The next reaction is a rearrangement of citrate to isocitrate.

substrates(reactants )	citrate (citric acid)
enzyme	aconitase
products	isocitrate

4. In this reaction, isocitrate is oxidized to alpha ketoglutarate. Being an oxidation reaction, electrons are removed and are transferred, in this instance, to NAD to form NADH. In addition, this oxidation results in the release of carbon dioxide from isocitrate (see yellow atoms) so that the total number of carbons remaining is reduced by 1 to 5.

substrates(reactants )	isocitrate	+ NAD
enzyme	isocitrate dehydrogenase
products	alpha ketoglutarate	+ NADH + CO2

5. In this reaction, the 5-carbon alpha ketoglutarate is converted into the 4-carbon succinate. This is an oxidation reaction (thus forming an NADH) that removes a carbon in the form of carbon dioxide. The remaining 4-carbon molecule will now be converted into oxaloacetate, the molecule that we needed to condense with acetyl CoA. The excess energy is conserved by the addition of Coenzyme A to the succinate thus forming succinyl CoA. 

substrates(reactants )	alpha ketoglutarate	+ CoA + NAD
enzyme	alpha ketoglutarate dehydrogenase
products	succinly CoA	+ NADH + CO2

6. In this reaction, the Coenzyme A is removed forming succinate. The energy that was stored in the linkage of the CoA to succinate is now used to attach a phosphate to GDP to form GTP. GTP is a close cousin to ATP and the cell has enzymes present that are capable of making an ATP from the energy in the GTP. This is not an oxidation reaction so no NADH is formed.

substrates(reactants )	succinyl CoA	+ ADP + PO4
enzyme	succinyl CoA synthetase
products	succinate	+ CoA + ATP

7. This reaction is oxidation reaction, however, unlike the other oxidations that you have met in the cycle, no carbons are lost. In this instance, the succinate is oxidized to fumarate. Since it is an oxidation, electrons and energy are released. However, the amount of energy released in this reaction is not enough to drive the reduction of NAD to NADH and so FAD (flavin adenine dinucleotide) is used in this reaction - When FAD accepts electrons (and is therefore reduced), it becomes FADH. 

substrates(reactants )	succinate	+ FAD
enzyme	succinate dehydrogenase
products	fumarate	+ FADH

8. This is a reaction that essentially rearranges the structure of fumrate into a molecule of malate.

substrates(reactants )	fumarate
enzyme	succinate dehydrogenase
products	malate

9. This is the 'last' reaction of the cycle. In this reaction, malate is oxidized to oxaloacetate. The electron acceptor for this reaction is NAD thus we form another NADH during this reaction. Since we have regenerated the OAA, all we need to begin another cycle is the addition of acetyl CoA.

substrates(reactants )	malate	+ NAD
enzyme	succinate dehydrogenase
products	oxaloacetate	+ NADH

IV. Electron Transport Chain  

The electron transport system is found in the mitochondrion and chloroplast of eucaryotes and in the plasma membrane of procaryotes. It consists of a series of carrier molecules which pass electrons from a high-energy compound to a final low-energy electron acceptor. Energy is released during these oxidation-reduction reactions to produce ATP.  NADH or FADH2 bring electrons to the electron transport system in the mitochondria.

The system contains membrane-bound electron carriers that pass electrons from one to another. When a carrier reduces another, some of the energy that is released as a result of that reduction is used to pump hydrogen ions across the membrane into the intermembrane space. The remaining energy is used to reduce the next carrier.

As a result of the electron transport system, hydrogen ions become concentrated in the intermembrane space.  The enzyme ATP synthaseis able to use the energy of this osmotic gradient to produce ATP as the hydrogen ions move under osmotic pressure through the enzyme back into the matrix of the mitochondrion.

Oxygen is the final electron acceptor. The low-energy electrons that emerge from the electron transport system are taken up by O2. The negatively charged oxygen molecules take up protons from the medium and form water (2H+ + 2e- + 1/2 O2 --> H2O).

Summary: 

Source from: 

1.http://faculty.clintoncc.suny.edu/faculty/michael.gregory/files/bio%20101/bio%20101%20lectures/cellular%20respiration/cellular.htm

2. http://www.austincc.edu/emeyerth/krebs.htm

Enzymes

Enzymes are protein molecules, and so are made up of amino acids. These amino acids are joined together in a long chain, which is folded into different shapes and is folded to produce a special 3D structure.

Structure

Normally, enzymes function as catalysts. Enzymes speed up a chemical reaction by loweing the activation energy needed to start the reaction.

Also, enzymes are required in minute amounts. Enzymes are very efficient molecules. They remain unchanged in the reactions they catalyse, the same enzyme molecules can be used over and over again. Enzymes are unique that each chemical reaction inside a cell is catalysed by a unique enzyme. (AKA enzyme specificity) Only molecules with exactly the right shapes will bind to the enzyme and react. These are the reactant  , or substrate, molecules.And, the part of the enzyme to which the reactant binds is called the active site. 

A substrate is ought to fit into an enzyme's active site. (Lock and Key Hypothesis: The enzyme is the lock, and the reactant is the key.)

Moreover, there are two types of enzyme inhibitors: one is called competitive inhibitor, and the other one is called non-competitive inhibitor.  

Last but not least, temperature and pH values would affect enzymes. Enzymes would change shapes under certain temperature/ pH level; therefore, shape changes would affect the function of enzymes. 

Summary :)