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.

Drunken Monkey Hypothesis

Craving a beer? Feeling bad about it because you think you might be addicted to alcohol? Don't feel bad because all humans are addicted to alcohol...here's why. According to the 'Drunken Monkey Hypothesis', proposed by Dr. Robert Dudley of the University of California- Berkeley, human beings are actually attracted to ethanol (the type of alcohol we drink) because of their huge dependence on fruit throughout our evolutionary journey. Fruit, contains ethanol, and our body craves it as if we were still foraging for food. Along with this hypothesis is our desire for sugars and fats. Why you ask? For the same reasons, however, it is a two-fold answer. Firstly, sugars and fats are very high in calories, fats to be exact are worth twice as many calories as proteins. While proteins are better for us nowadays, if one of our ancestors was able to get double the energy to survive thousands of years ago, that was the better option (obviously). Also, fats and sugars were a whole lot more rare than they are today, so that coupled with the fact that we could gain more energy from these 'horrible' items, over time, ingrained a desire in our genes to crave sugar, fats, and alcohol. So whenever you feel bad about drinking, blame your ancestors of thousands of years ago.

Opposites Attract

I'm sure everybody has heard the saying 'opposites attract' in reference to a multitude of different things, whether that be magnetic charges, animal interactions, etc. Well, research over the last decade or so has come up with actual evidence for this being the case, not only in non-human relationships, but also in human relationships. The basis for this claim rests in the quest for organisms to have stronger, more diverse DNA, which for the most part, results from more exposure to varying nucleotide sequences. There is a complex found in animals (as well as, humans) called the major histocompatibility complex (MHC), which participates in cell recognition, as a major component of the immune system. It is also well known that there are harmful, deleterious effects that occur from mating between family members. This of course has a high probability of hampering offspring development. Due to these deleterious effects resulting from interbreeding, there is actually evidence from studies that people and other animals instinctively (built in from evolution) seek out mates (more so on the female's part because it deals with when they are in a fertile state). What is the way they do this you ask? Through pheromones. Without getting too into the specific details, the DNA and subsequent proteins, code and function in producing representations of the MHC and other DNA components in the form of pheromones that the males and females secrete. The secretions are sensed so that the females and possibly males (in some other form) can seek out a mate, all in an effort to diversify their DNA for evolutionary stability purposes.

FOOD FOR THOUGHT: Other pheromones that females secrete out of the arm pits, are responsible for the alignment of menstruation cycles with women living in a house together for a extended period of time. The pheromones are sensed by glands in the nasal cavity, which send these signals to the brain via an efferent nerve. The brain then determines when the menstruation occurs. Another evolutionary stable move, because animals that have young at the same time, with other animals they are close to, can help raise the offspring, thus reducing the fitness cost (ex: lionesses carrying for cubs that are not theirs).