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Items: 3

1.

Glycolysis Pathway

In glycolysis, the six-carbon sugar glucose is oxidized and split in two halves, to create two molecules of pyruvate (3 carbons each) from each molecule of glucose. Along the way, the cell extracts a relatively small amount of energy from glucose in the form of ATP, 2 ATP molecules collected for each glucose molecule that starts down the glycolytic path. The pyruvate produced has one of three metabolic fates, to either become acetyl-CoA, ethanol, or lactate. When oxygen is available, the pyruvate can be converted to acetyl-CoA and enter the Krebs Cycle, where the acetyl-CoA will be completely oxidized and generate ATP through oxidative phosphorylation. Fermentation is much less efficient than oxidative phosphorylation in making ATP, creating only 2 ATP per glucose while oxidative phosphorylation creates 36 ATP per glucose in mammalian cells. Oxidative phosphorylation does not work in the absence of oxygen, however, and in the absence of oxygen glycolysis is forced to a halt due to a lack of NAD+, unless NAD+ is regenerated through fermentation. In mammalian muscle, strenuous exertion can create conditions in which oxygen is consumed faster than blood can provide it, forcing the muscle to use fermentation and create lactic acid; it is the lactic acid that makes your muscles sore after a workout. There are ten enzymes that catalyze the steps in glycolysis that convert glucose into pyruvate, and the entire pathway is located in the cytoplasm of eukaryotic cells. The activity of the pathway is regulated at key steps to ensure that glucose consumption and energy production match the needs of the cell. The steps along the pathway each involve a change in the free energy of the products and reactants, and as long as the overall change in free energy is negative, the reaction continues forward, like water flowing down hill to its lowest energy point. The key steps in the regulation of glycolysis, or any pathway, are those that catalyze the rate-limiting, irreversible steps along the pathway. In glycolysis in mammals, the key regulatory enzyme is phosphofructokinase, which catalyzes the rate-limiting committed step. Phosphofructokinase is activated by AMP and inhibited by ATP, among other regulatory mechanisms. Thus, when ATP is low (and AMP is high), phosphofructokinase will be activated and generate more ATP. Similarly, when ATP is abundant, phosphofructokinase will be inhibited to prevent wasting glucose on making energy when it is not needed. Failure to provide energy can have lethal consequences for cells - the absence of oxygen caused by a stroke or a heart attack that prevents ATP generation can have lethal consequences for the cells involved. Cancer cells often generate energy through glycolytic fermentation more than oxidative phosphorylation, suggesting that manipulation of metabolism may provide a therapeutic strategy. Well known glycolytic enzymes such as glyceraldehyde-3-phosphate dehydrogenase may play roles in other cellular processes such as apoptosis. [from NCI_BioC]

MedGen UID:
268138
Concept ID:
C1512233
Molecular Function
2.

Tricarboxylic acid cycle disorder

MedGen UID:
832806
Concept ID:
CN227000
Disease or Syndrome
3.

Citrate Cycle (TCA Cycle) Pathway

The citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form of acetate, derived from glycolysis and pyruvate oxidation of carbohydrates and from beta oxidation of fatty acids. The two-carbon acetyl group in acetyl-CoA is transferred to the four-carbon compound of oxaloacetate to form the six-carbon compound of citrate. In a series of reactions two carbons in citrate are oxidized to CO2 and the reaction pathway supplies NADH for use in the oxidative phosphorylation and other metabolic processes. The pathway also supplies important precursor metabolites including 2-oxoglutarate. At the end of the cycle the remaining four-carbon part is transformed back to oxaloacetate. According to the genome sequence data, many organisms seem to lack genes for the full cycle, but contain genes for specific segments. [from NCI_KEGG]

MedGen UID:
273947
Concept ID:
C1516586
Molecular Function
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