Question

1. Describe how the unique reactions of GNG represent a pathway distinct from glycolysis based on the free change of the reaction catalyzed by the glycolysis enzyme, phosphofructokinase
2. Describe the functions of phosphoglucomutase and glucose 6-phosphatase enzymes in the pathway connecting glycogen breakdown to glucose export in liver cells.

3. Gluconeogenesis (GNG)

   Review coupled reactions (McKee page 120-121). It is useful and customary to express the number of GTP, UTP, or other nucleotides consumed or produced in a pathway as equivalent to ATP. A cellular reaction that exchanges the terminal phosphate between ADP and another nucleoside diphosphate is catalyzed by nucleoside diphosphate kinase (McKee page 347) One of the reactions of GNG consumes GTP. The task is to find the overall reaction that gives the equivalent change in ATP.

Answer 1

Answer.

The metabolic processes Glycolysis and Glycogenesis are related to carbohydrete metabolism. In glycolysis glucose molecule is broken down whle in glycogenesis glucose molecule is formed.

In Glycolysis, two molecules of ATP (Adenosine triphosphate) is generated that provide energy to the cell for performing different functions required in metabolic processes. Apart from the ATP, two pyruvate molecules are also formed and can be utilised in other metabolic pathways such as in gluconeogenesis (Pyruvate gets converted to lactate), Citric acid cycle (Pyruvate converted to oxaloacetate/citric acid) and transamination reaction (conversion of pyruvate to alanine). While in the process of glycogenesis, glucose is synthesised by amino acids/pyruvate/lactate/fatty acids/glycerol (non carbohydrate residues).

Glycolysis is prevelent in every cell. It also occur in the cells where mitochondria is absent (Red blood cells) and provide instant energy in the form of ATP while Glycogenesis is only restricted to liver/hepatic cells in the organisms and mainly occurs during fasting.

Both of the metabolic functions are coupled with the interaction of various catalytic enzymes. Some of the enzymes are regulatory to the pathways. They can upregulate and down regulate the pathways as requirement of glucose residues and energy needed.

The rate limiting enzyme for the glycolysis is Phosphofructokinase-1 while for gluconeogenesis, it is fructose 1,6-bisphosphatase.

Phosphofructokinase-1 gets activated when the AMP/ADP level is high and inhibited when ATP level is high. It is also affected by (activated/inhibited) by the feed back inhibition of the citrate (product of the TCA cycle). Vice versa is applied in case of fructose 1,6-bisphosphatase (fructose 1,6-bisphosphatase gets activated when AMP/ADP level is low and ATP level is high and citrate level is high). Similarly, in gluconeogenesis pathway, fructose 1,6-bisphosphatase is inhibited when excess of glucose is already present in the liver cell and activated when glucose is scarced.

The hormones Insulin and Glucagon are responsible for the upregulation of both metabolic processes glycolysis and gluconeogenesis respectively.

Insulin down regulates gluconeogenic metabolic pathways while glycolysis is down regulated by Glucagon.

There are many other pathways where energy is generated either in the form of ATP/GTP/UTP/NADPH by the shunting of the glucose molecules generated by gluconeogenesis pathways.

In the process of glycolysis there is net gain of two ATP molecules at the expense of one glucose residues while six ATP/GTP is required to generate aech glucose molecule. Hence, it can be concluded that glycolysis is energy donating process while gluconeogenesis is energy dependent process.

Glucose can also enter in pentose phosphate pathway (PPP) occuring in cytosol of liver/adrenal cortex/RBCs generating nicotinamide adenine dinucleotide phosphate (NADPH) and ribose 5-phosphate from glucose 6-phosphate in the presence of Glucose 6-phosphate dehydrogenase. Cholesterol synthesis/steroid synthesis/reduction of glutathione requires the energy source in the form of NADPH while purine and pyrimidine (nucleotide) synthesis require ribose 5-phosphate. Haemolytic anaemia is a condition which occurs during deficiency of Glucose 6-phosphate dehydrogenase leading to insufficient formation of NADPH. NADPH is essential for inhibiting free radical outburst by reducing glutathione that prevent damage of RBC membranes by excess of hydrogen peroxide and free radicals.