Krebs Cycle Broken Down

The Krebs cycle, also known as the Citric Acid cycle, is a very important process in cellular respiration. Without this portion, respiration would not be possible. This is because the Krebs cycle uses the pyruvate molecules from glycolysis to produce high energy molecules essential for the electron transport chain (ETC) which follows soon after. Here we will go over the different processes that occur during the Krebs cycle, breaking it down molecule by molecule.

FUNCTION: To produce high energy molecules such as NADH and FADH2, which act as electron carriers in the electron transport chain. The ETC is where most of the cell's ATP (energy currency) is produced. Additionally, many different precursor molecules are made that can be utilized by a cell.

The Krebs cycle is what is known as Amphibolic, in that it is both catabolic (breaks down molecules) and anabolic (builds molecules).

LOCATION: Mitochondrial matrix

NET PRODUCTS: 2 GTP, 6 NADH, 2QH2 (ubiqinone), 2 FADH2, 2 CO2, minimal ATP

Step 1. Pyruvate molecules (3-carbon) from glycolysis are converted into another type of molecule called Acetyl-CoA in a process known as pyruvic oxidation. This conversion occurs when the pyruvate is broken down by an enzyme, releasing a carbon atom which goes on to form carbon dioxide (CO2). The 2 remaining carbon molecules bond with coenzyme A forming Acetyl-CoA. During this process, electrons and a hydrogen ion are passed to NAD+, thus oxidizing the pyruvate, hence the name of the process.

Step 2. The Acetyl-CoA then enters the Krebs cycle. It initially combines with a 4-carbon molecule called oxoaloacetic acid, forming a 6-carbon molecule of citric acid (citrate). This reaction is catalyzed by the enzyme citrate synthase.  Upon this formation, the coenzyme A is released.

Step 3. The citrate molecule is then dehydrated (H20 molecule is removed) and then rehydrated by the the enzyme aconitase. The resulting molecule is just a rearranged form of citrate known as isocitrate.

Step 4. Next, isocitrate undergoes what is known as a oxidative carboxylation, which simply means that a carbon and hydrogen are given off. The result of this is a 5-carbon molecule called alpha-ketoglutarate. This process is catalyzed by the enzyme isocitrate dehydrogenase. Additionally, the carbon that broke off forms CO2, while the hydrogen reduces NAD+ to form NADH.

Step 5. In the next reaction, alpha-ketoglutarate has yet another carbon molecule removed and is then transferred to a CoA molecule by the enzyme alpha-ketoglutarate dehydrogenase. The resulting product is a 4-carbon molecule of Succinyl-CoA. Additionally, CO2 and NADH is formed.

Step 6. After succinyl-CoA is formed, the molecule then undergoes the removal of the CoA carrier, resulting in the production of succinate. Additionally, the enzyme succinyl-CoA synthetase that removes the CoA also produces GTP through substrate level phosphorylation (phosphate molecule directly added to another molecule). GTP is a high energy molecule similar to ATP.

Step 7. Next, succinate is dehydrated by the enzyme succinate dehydrogenase. The resulting product is furmate.

Step 8. Furmate is then hydrated by enzyme furmase to form malate.

Step 9. Lastly, the malate is dehydrogenated by the enzyme malate dehydrogenase, forming the original molecule oxaloacetate. From this reaction, NADH and H+ are also produced.

Once the oxaloacetate molecule has been regenerated, the Krebs cycle can repeat. With the completion of this cycle, the electron transport chain (ETC) and subsequent oxidative phosphorylation occurs, resulting in the production of 36-38 ATP, providing the cell with energy.

Renin-Angiotensin-Aldosterone Made Simple

The body has many systems that work together in order to maintain homeostasis. The renin-angiotensin-aldosterone pathway is no different. It has 3 functions: (1) to maintain a proper blood pressure/blood flow, (2) to maintain the right concentration of sodium (Na+) in the blood, and finally, (3) to maintain the right amount of water in the blood. To make sure that these 3 things stay at proper levels, several hormones and several organs work together to accomplish this task. Now to break the pathway down!

RENIN-ANGIOTENSIN-ALDOSTERONE PATHWAY

This process starts out in the kidneys, but becomes very systemic (all over body) throughout the pathway. It does return to the kidneys at several instances. 

1. Low blood pressure/blood flow is sensed by the Juxtaglomerular apparatus in the kidney (which are cells next to the glomerulus). This is because a decrease in Na+ will reduce the amount of water in the blood, thus the blood will have a lower pressure. This follows the principle of osmosis, which states that water will diffuse to areas that have highly concentrated solutes.

2.  In response to this, the glomerulus  (the bed of capillaries that is wrapped up by Bownan's capsule and is next to the proximal convoluted tubule) releases a hormone known as renin into the blood stream.

3. Renin then moves to the liver, where is converts an inactive peptide (protein) angiotensinogen to an active angiotensin I.

4. Angiotensin I then travels to the lungs where an enzyme known as the Angiotensin Converting Enzyme (ACE), converts Angiotensin I to Angiotensin II. One effect Angiotensin II has on the body is in its ability to constrict blood vessel, thus increasing blood pressure. Another function of it is to stimulate the adrenal glands on top of the kidneys to produce the hormone Aldosterone.

5. Aldosterone stimulates the reabsorption of sodium (Na+) in the distal convoluted tubules. Increasing sodium reabsorption means that water and chloride (Cl-) will follow, thus increasing blood volume.

6. An increase in blood volume may also trigger the release of a hormone known as Atrial Natriuretic Hormone, which inhibits the release of Aldosterone, keeping the body's water and sodium levels at the homeostatic levels.This last step is known as a negative feedback loop.

And that is the renin-angiotensin-aldosterone pathway. If one can grasp the concept of osmosis and how water follows highly concentrated solutes, one will be able to understand blood pressure and other methods of osmoregulation (water balancing) in the kidneys.