20241206_Carbs2

The main precursors for glucogenesis are predominantly lactic acid, glycerol, and amino acids.

Gluconeogenesis primarily occurs in the liver, with the kidney cortex and intestinal epithelia as minor contributors.

1. Carboxylation of pyruvate to oxaloacetate – catalyzed by pyruvate carboxylase.

2. Decarboxylation of oxaloacetate to PEP – catalyzed by PEP carboxykinase. This step essentially reverses the reaction catalyzed by pyruvate kinase.

3. Hydrolysis of fructose 1,6-bisphosphate – catalyzed by F,16-bisphosphatase. This reverses the PFK reaction in glycolysis.

4. Hydrolysis of glucose-6-phosphate to glucose – catalyzed by G-6-phosphatase. This enzyme reverses the reaction catalyzed by hexokinase (or glucokinase).

1 molecule of hexose yields 12 NADPH and 6 CO2.

The enzymes of the Pentose Phosphate Pathway are found in the cytosol. No ATP is required once glucose-6-phosphate (G-6-P) is formed.

The Pentose Phosphate Pathway is the primary source of reduced NADP+, which is essential for the biosynthesis of fatty acids and cholesterol.

The Pentose Phosphate Pathway provides a source of pentose (ribose), which is required for the biosynthesis of nucleotides and nucleic acids.

The initial substrate is beta-Glucose 6-phosphate, and it is catalyzed by the enzyme Glucose 6-phosphate dehydrogenase.

The reactants are C5 + C5, and the enzyme is transketolase.

The products are ribulose-5-phosphate, carbon dioxide (CO2), and two molecules of NADPH.

The overall reaction is: 6 G-6-P + 12 NADP+ → 5 G-6-P + 6 CO2 + 12 NADPH + Pi, which is equivalent to the complete degradation of a hexose unit.

NADPH enters the mitochondria by reacting with NAD+ in a reaction catalyzed by nucleoside transhydrogenase, resulting in NADP+ and NADH.

The net ATP production is 35 ATP, calculated from 12 NADPH formed (12 x 3 ATP = 36) minus 1 ATP used for G-6-P synthesis.

Under anoxic conditions, glucose-6-phosphate (G-6-P) is diverted to the pentose phosphate pathway (PPP), leading to the production of NADPH, which is then used for fatty acid synthesis. This metabolic shift is important for maintaining energy production and biosynthesis when oxygen is limited.

The pentose phosphate pathway is important in the metabolism of erythrocytes (red blood cells) for maintaining membrane structure. It provides NADPH, which is essential for protecting cells from oxidative damage and for the synthesis of nucleotides and nucleic acids.

Glucose-6-phosphate dehydrogenase catalyzes the rate-limiting step in the pentose phosphate pathway, generating NADPH, which is essential for protecting the red blood cell membrane against oxidative damage.

Glutathione is a small peptide made up of three amino acids: glutamate, cysteine, and glycine.

NADPH reduces the disulfide form of glutathione to its sulfhydryl form by transferring electrons to FAD in glutathione reductase, which then transfers them to the disulfide bridge of glutathione.

Reduced glutathione is essential for maintaining the normal structure of red blood cells (RBC).

G6PD (Glucose-6-phosphate dehydrogenase) facilitates the conversion of glucose-6-phosphate to 6-phosphogluconate, which results in the reduction of NADP to NADPH. This process is crucial for maintaining the cellular levels of NADPH, which is essential for various biosynthetic reactions and for protecting against oxidative stress.

NADPH acts as a reducing agent in the non-enzymatic reduction of oxidized pamaquine to reduced pamaquine, facilitating the transfer of electrons and protons in the process.

This reaction is significant because it leads to the production of the hydroxyl radical (OH•), which is highly reactive and can damage polysaccharides, DNA, proteins, and lipids. This contributes to the mechanisms of chronic iron toxicity.

Glutathione acts as a reducing agent that helps remove peroxides generated by oxidative agents. In G6PD deficiency, lower levels of glutathione make cells more susceptible to hemolysis due to oxidative stress.

Nonenzymatic oxidative agents such as pamaquine generate peroxides, which can lead to oxidative damage and hemolysis in red blood cells, especially in individuals with G6PD deficiency.

Oxidative attack by reactive oxygen species leads to hemolysis of red blood cells, particularly in those with lowered glutathione levels, as seen in G6PD deficiency.

Glutathione helps maintain the reduced form of sulfhydryl groups in hemoglobin (Hb). In G6PD deficiency, lower levels of glutathione lead to increased susceptibility to hemolysis due to oxidative stress.

In G6PD deficiency, the sulfhydryl groups of hemoglobin cannot maintain their reduced form, leading to crosslinking of hemoglobin and the formation of Heinz bodies on cell membranes.

Oxidative stress makes red blood cell membranes more prone to deformation, which increases the likelihood of lysis in G6PD deficiency.

Muscle tissues store between 250-450g of glycogen, which is about 0.7-1.3% by weight.

Glycogen contains α(1→4) bonds and α(1→6) bonds. α-Amylase acts on the α(1→4) bonds to produce malto-oligosaccharides and oligosaccharides.

In the liver, glycogen synthesis increases with excess glucose from the diet, while breakdown is activated when the brain needs glycogen stores. Glycolysis is inhibited during glycogen breakdown. In muscle, glycogen is utilized when energy demands increase, with glycolysis and breakdown activated simultaneously, controlled by muscular contraction events and calcium ions as signals.

Nonreducing ends are crucial for enzymatic action as they provide accessible sites for enzymes like α-amylase to initiate the breakdown of polysaccharides, allowing for efficient energy release and utilization.

1. α-1,4 to α-1,4 glucan transferase: Transfers three residues as a trisaccharide unit to another branch, exposing the glucose unit attached by the α1,6-glucosidic bond.

2. Amylo 1,6-glucosidase: Hydrolyzes the α1,6-glucosidic bond to release free glucose.

Free glucose is released by the enzyme glucose-6-phosphatase, which catalyzes the conversion of G-6-P to free glucose.

The first step in glycogen biosynthesis is the formation of G-6-P from glucose and ATP, catalyzed by hexokinase.

The glycemic index classifies foods based on their potential to raise blood glucose levels.

The glycemic index indicates the body's insulin response to carbohydrate-containing food.

Foods with a high glycemic index trigger a sharp rise in blood glucose, followed by a dramatic fall.

Foods with a low glycemic index trigger slower and more modest changes in blood glucose levels.

Insulin is released by the pancreas in response to elevated blood glucose levels. It facilitates the transport of glucose into cells and promotes the conversion of glucose into glycogen for storage, thereby lowering blood glucose levels.

Glucagon is released by the pancreas when blood glucose levels are low. It stimulates the breakdown of glycogen into glucose and increases gluconeogenesis, raising blood glucose levels back to normal.