Question

Describe the pathway of free glucose in the bloodstream through its complete oxidation to CO₂ and H₂O during cellular respiration. Include relevant signaling molecules, metabolic pathways, key intermediates and locations of all metabolic steps.

Answer 1

Answer:

The overall balanced reaction of cellular respiration is:

C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + ATP                   

glucose + oxygen → carbon dioxide + water + energy         

In this reaction, glucose is oxidized and oxygen is reduced.

Insulin:

Insulin promotes the storage of glucose in the liver in the form of glycogen, while decreasing the blood glucose levels. It also stimulates the synthesis of fatty acids in the liver. If the glycogen stores of liver is saturated, the lipid synthesis is promoted, which are exported from the liver as lipoproteins. The free fatty acids provided by lipoproteins enable the adipose tissue to synthesize triglycerides.

Within adipose tissue, insulin inhibits the breakdown of fatty acids, by inhibiting the action of lipase. Within the adipocytes, the glucose is used to synthesize glycerol (insulin facilitates the entry of glucose into adipose tissue). Glycerol and fatty acids, both are used to synthesize triglycerides in the adipose tissue. Thus, insulin facilitates the synthesis of triglycerides in the adipose tissue by these two mechanisms.

Insulin and glucagon are the two hormones produced by pancreas. They both are chemically protein. But, the physiological actions produced by both the hormones are quite opposite. Insulin reduces the blood glucose level, whereas, glucagon raises the blood glucose level.

Insulin influences glucose metabolism in various tissues, including liver. In liver, it inhibits the glycogen breakdown (glycogenolysis) and the synthesis of new glucose molecules (gluconeogenesis), but stimulates glycogen synthesis. Whereas, the effects produced by glucagon are opposite to insulin. So, these hormones act antagonistic to one another to maintain homeostasis.

The increased levels of blood glucose concentration further activates the Beta Islets of pancreatic langerhans cells to synthesize and release active insulin into the blood stream to act on the blood glucose levels and to further maintain glucose homeostasis.

Preproinsulin (110 amino acids): the inactive preproinsulin will be converted to proinsulin with 51 amino acids of 5.8 kDa molecular weight. Later the proinsulin will be transported to the endoplasmic reticulum for maturation by the golgi vesicles in which it is cleaved to produce active insulin and C-peptide. Finally these two products gets stored in the secretary granules along with islet amyloid polypeptide or amylin. This active insulin will be released into the blood stream by cellular vesicular trafficking. A high affinity calcium sensor in pancreatic beta cells reported that is synaptotagmin.

Glucose metabolism:

Glucose transporters of both GLUT1 and GLUT3 are potentially involved in basal glucose uptake and they transport glucose recurrently into the cells at a constant rate Km and at 1mM concentration.

Normally glucose enters into the cell by passive facilitated diffusion via GLUT 4 (muscle or adipose cells) or via GLUT-2 (brain, kidney, pancreatic beta cells) and will be converted to glucose -6-phosphate (by enzyme glucokinase) later by oxidation process it produces ATP that acts on Kir6. 2 channel subunits of the pancreatic beta-cell. The stimulation of pancreatic Kir6 2 channel subunits results in activation of calcium channels (by depolarization) and further stimulate the vesicular release of insulin from pancreatic beta cells into the blood stream which acts on glucose.

Signaling molecules, metabolic pathways:

Two enzymes MAP-kinase and phophoionositidine-3-kinase are responsible for insulin activity on metabolic process. The glucose which isolated by PIK-3 will be sent to the mitochondria where it undergo oxidative phosphorylation to produce ATP. PIK-3 also enables insulin action for further lipid metabolism and glycogen synthesis by glycolysis.

The pathway of free glucose in the bloodstream through its complete oxidation to CO₂ and H₂O during cellular respiration:

Cellular respiration is the utilization of oxygen by the cell for the synthesis of metabolic products such as sugars, fats, proteins etc. In humans, cellular respiration takes place through the mitochondria (power hoses of the cell), in which the most of the metabolic processes takes place. Blood carries the oxygen to each and every cell in the body and again collects the carbon dioxide.

C₆H₁₂O₆ (s) + 6 O₂ (g) → 6 CO₂ (g) + 6 H₂O (liq) + heat

The first step in cellular respiration is glycolysis.

Glycolysis is an anaerobic process, through which one glucose molecules is breakdown into two molecules of three carbon pyruvate. The glycolysis of each glucose molecule generates 2 ATP molecules.

Glucose + 2 NAD⁺ + 2 P_i + 2 ADP → 2 pyruvate + 2 NADH + 2 ATP + 2 H⁺ + 2 H₂O + heat.

Citric acid cycle:

The pyruvate generated by the glycolysis is converted into acetyl-CoA that enters into the citric acid cycle. Citric acid cycle involves a series of reactions that occur in the presence of oxygen. Citric acid cycle generates NADH, which enters into the oxidative phosphorylation process. This cycle occurs in mitochondrial matrix and generates one ATP molecule only.

Coenzyme A: It is a thiol derivative that further reacts with a acetyl component of carboxylic acids to produce thioesters and finally enable to transfer fatty acids from cytosol to mitochondria.

Oxidative phosphorylation:

Glycolysis (breakdown of glucose), oxidation of fatty acids and citric acid cycle releases NADH (hydrohenated nicotinamide adenine dinucleotide) and FADH₂ (hydrogenated flavin adenine dinucleotide) molecules. These molecules carry electrons with high transfer potential. The oxygen present in the mitochondria is reduced by these electrons to water molecules; this process produces a very high amount of energy (in the form of ATP (adenosine triphosphate)).

“Oxidative phosphorylation (occurs in cristae of mitochondria)” is an aerobic process that involves a series of reactions, which include the transfer of electrons from the NADH or FADH₂ to oxygen. This process involves the transfer of electrons (oxidation) by a series of electron carriers (electron transport system (ETS)) and attachment of phosphate group (phosphorylation).

In all the above reactions the inactive GDP/ATP will converted to GTP/GTP (in the conversion of Succinyl co enzyme A rection) by the active addition of inorganic high energy phosphate (iP) or pyrophosphate (in case of AMP or GMP). This process is done by ATP synthase by using the protons at the F1- particles (Fernadez moran particle) in the inner mitochondrial membrane. The active from of the phosphorylases only can promote ATP or GTP energy molecule synthesis because these enzymes possess the active site to carry the high inorganic phosphate and add them to the substrate molecule competitively in a reversible manner.

The free energy released by oxidative phosphorylation contributes to the major part (nearly above 90%) of energy expenditure of our daily activities.

Key reactants and products of fermentaiton: Fermentation is a process of anaerobic catabolism. It is the continuation of glycolysis in the absence of oxygen. However, this process needs the supply of NAD+ as an electron acceptor. NAD+ is produced in aerobic conditions, fermentation occurs as long as NAD+ reserves are available. During fermentation, pyruvate is metabolized to lactic acid and produces 2 molecules of ATP.