Glycolysis

Carbohydrates serve as the main energy source for organisms. In the diet, carbohydrates are primarily found as polysaccharides (such as starch) and disaccharides (including sucrose, lactose, and maltose). These carbohydrates are broken down into monosaccharides, which are then absorbed into the bloodstream. Glucose, a key monosaccharide, acts as the main fuel for cellular and tissue metabolism. Other monosaccharides are also converted into glucose. Once in the body, glucose undergoes various metabolic processes to generate energy.

1.0What is Glycolysis?

Glycolysis, also referred to as the Embden-Meyerhof-Parnas (EMP) pathway in honour of pioneers Gustav Embden and Otto Meyerhof, is a metabolic process in which a single glucose molecule is transformed into two pyruvate molecules. This pathway, consisting of 10 enzyme-catalyzed steps, occurs in the cytoplasm of nearly all tissue types.

2.0Steps of Glycolysis

• The process consumes 2 ATP molecules initially. During the second phase, glyceraldehyde-3-phosphate molecules are transformed into pyruvate, producing 4 ATP and 2 NADH molecules in the process.
• In all living organisms, whether aerobic or anaerobic, the first step in cellular respiration is the partial breakdown or oxidation of glucose into two molecules of pyruvic acid, a process known as glycolysis. 
• This phase is common to both aerobic and anaerobic respiration. In anaerobic organisms, glycolysis is the sole process in respiration.
• In plants, glucose is obtained from sucrose, a product of photosynthesis, or from starch, a storage carbohydrate. Sucrose is broken down into glucose and fructose by the enzyme invertase, and these monosaccharides enter the glycolytic pathway.
• Glycolysis occurs in the cytoplasm of the cell and is independent of oxygen, meaning it can proceed with or without the presence of O2. The process involves a series of ten enzymatic reactions. Glucose and fructose are first phosphorylated by the enzyme hexokinase to form glucose-6-phosphate and fructose-6-phosphate, respectively. 
• The phosphorylated glucose then isomerizes to produce fructose-6-phosphate. From this point, the metabolic pathways of glucose and fructose converge.In glycolysis, a series of ten reactions, each catalyzed by different enzymes, leads to the production of pyruvate from glucose.

End Product of Glycolysis

1. One molecule of glucose breaks down to form two molecules of pyruvate.

2. During this process, 2 ATP molecules are consumed, and 4 ATP molecules are produced, resulting in a net gain of 2 ATP molecules.

3. Additionally, 2 hydrogen atoms are generated and are accepted by NAD, converting it to NADH + H+. These hydrogen ions are then transferred to the electron transport system.

3.0Fate of Pyruvate

• The pyruvate produced through glycolysis can be further processed through three catabolic pathways:

1. Under aerobic conditions, pyruvate is fully oxidized into CO2 and H2O via  citric acid cycle.

2. In anaerobic conditions, such as in some microorganisms and in skeletal muscles under low oxygen, pyruvate is reduced to lactate through lactic acid fermentation.

3. In certain plant tissues, invertebrates, and microorganisms under hypoxic or anaerobic conditions, pyruvate is converted into ethanol and CO2 through ethanol (alcohol) fermentation.

4.0Glycogenesis

• Glycogenesis is the process through which glucose is converted into glycogen. While the liver and muscles are the primary sites for glycogenesis, this process can occur in all tissues to some extent. Glycogenesis is crucial as it allows excess glucose to be stored as glycogen, which can be utilized when needed. 

5.0Steps in Glycogenesis

• For glycogen synthesis to occur, a pre-existing glycogen chain, known as a glycogen primer, is required. 
• UDP-glucose (UDP-G) transfers a glucose molecule to this glycogen primer. In the presence of the enzyme glycogen synthase, a glycosidic bond is formed between the C-1 of the glucose from UDP-G and the C-4 of a terminal residue of the glycogen primer, releasing UDP in the process. 
• This elongation of the glycogen chain happens one glucose unit at a time through successive α 1-4 linkages. Glycogen synthase is the key enzyme regulating this process and can only add glycosyl residues if the polysaccharide chain has more than four residues.
• Once the chain reaches a minimum of 11 glucose residues, the branching enzyme comes into play. This enzyme transfers a segment of the α 1-4 chain (at least six glucose residues) to a neighbouring chain, creating an α 1-6 linkage and forming a branching point. 
• These branches then grow further through additional α 1-4 glycosyl units and subsequent branching. The resulting glycogen is stored in the liver and muscles.

6.0Deficiency Diseases of Carbohydrates

1. Acidosis: During carbohydrate starvation, the body undergoes a metabolic shift from glycolysis (the breakdown of glucose) to lipolysis (lipids) and ketogenesis to meet its energy requirements. This transition leads to the production of keto acids, which can elevate the acidity levels in the blood and tissues. When the pH of arterial blood falls outside the optimal range of 7.35 to 7.45, it can result in significant cellular damage that may be irreversible.

2. Ketosis: Carbohydrate deficiency leads to the formation of ketone bodies in the liver through the breakdown of fatty acids and the deamination of amino acids, resulting in ketosis. Ketosis can cause prolonged dehydration and decreased bodily secretions.

3. Hypoglycemia: Insufficient glucose availability due to a severe lack of carbohydrates leads to a decrease in blood sugar levels. It occurs when blood glucose levels drop below 70 mg/dL, manifesting typical symptoms such as dizziness, fatigue, and distress.

4. Constipation: Dietary fiber, an essential component found in carbohydrate-rich foods, is known to prevent colorectal cancer and aid digestion. Insufficient intake of dietary fiber can result in constipation.