Sugar is a general term used to describe small mono and disaccharides found in food. Monosaccharides include glucose, fructose, and galactose. Disaccharides include sucrose(a disaccharide of glucose and fructose), lactose(galactose and glucose) and maltose (glucose and glucose). Glucose is absorbed into the human body by glucose transporters(GLUT1, GLUT2, GLUT3, GLUT4). Once in the blood glucose is stored in the form of glycogen in humans.

Glucose is broken down and converted to energy(ATP) by glycolysis, a process by which glucose moves through a sequence of enzymes. Many of the reactions involved in glycolysis require magnesium as an enzyme cofactor. Blood sugar levels are regulated by the release of glucagon and insulin. Insulin removes glucose from the blood stream, moving it into the cells. Glucagon raises the blood sugar concentration, extracting glucose from the cells.

Excess amounts of glucose that are not used for fuel are turned into fat. This is because the liver converts the glucose-6-phosphate into pyruvate and ultimately acetyl CoA. If the Acetyl CoA is not used to produce energy it is converted into fatty acids which are released into the blood as VLDL's and stored in adipose tissue as fat.

Glucose is the primary energy source of the human brain, red blood cells, reproductive organs, embryonic tissue and the renal medulla.



Common Carbohydrates

Sucrose

Sucrose is the table sugar we are most familiar with. It is extracted mostly from sugarcane, a plant with high sucrose concentration. It is the most common disaccharide seen in living organisms. In a sucrose molecule, an alpha-1,2-glycosidic bond connects glucose and fructose molecules together. Sucrose is known as a nonreducing sugar, meaning it dose not react with oxidizing agents. In this case, the oxygens in the aldehyde functional groups of both the fructose and glucose molecules are occupied in the bond connecting the two rings and therefore there is now reaction with the oxidizing agent.

Maltose

Maltose is a disaccharide of two glucose molecules connected by an alpha-1,4-glycosidic bond. It comes from malt, the juices of cereal grains. Maltose acts as a reducing sugar because the hemiacetal functional group is at equilibrium with its aldehyde form, exposing the oxygen of the aldehyde form for an oxidation-reduction reaction.

Lactose

Lactose is known for its presence in milk. Some people have a deficiency of lactase, the enzyme that break lactose down, this is known as lactose intolerance. Lactose is a disaccharide of glucose and galactose connected by a beta,1-4, glycosidic bond. Lactose is considered a reducing sugar.

Glucose(C6H12O6)

Glucose molecules are six membered ring structures with the ring made up of five carbons and one oxygen molecule. The carbons are attached to OH functional groups making glucose water soluble.



Sugar and Health

Dietary guidelines recommend to limit consumption of added sugars to less than 10% of calories per day. The term "added sugars" includes syrups, sucrose, corn syrups, sugar, maltose, honey, fructose, nectars, and any type of sugar. A high intake of added sugar has been associated with obesity, diabetes, liver effects, and a variety of other hormonal effects. Excess sugar that the body dose not utilize for energy is turned into fat.

Glycolysis

During glycolysis, one glucose molecule is acted on by a number of different enzymes with the final result being 2 molecules of pyruvate. This process results in the production of 2 pyruvate molecules, 2 ATP molecules(net gain) and 2 NADH molecules. The NADH molecules are converted to NAD+ by the electron transport chain within the mitochondria, producing more ATP through aerobic respiration. Glycolysis occurs in the cytoplasm of cells.

Steps of Glycolysis:

1) The hydroxyl group on the #6 carbon is phosphorylated forming glucose-6-phosphate.

2) Glucose-6-phosphate is converted into fructose-6-phosphate by the enzyme phosphohexose isomerase.

3) Fructose-6-phosphate is further phosphorylated by the enzyme PFK-1, producing fructose-1,6-bisphosphate. This reaction is irreversible.

4) Aldolase (fructose-1,6-bisphophate aldolase) cleaves fructose-1,6-bisphophate through a condensation reaction to produce glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

5) Triose phosphate isomerase converts the dihydroxyacetone phosphate into glyceraldehyde-3-phosphate. Only the glyceraldehyde-3-phosphate can move on to the next step of glycolysis, the remaining dihydroxyacetone phosphate is converted into glyceraldehyde-3-phosphate so it too can continue through glycolysis.

6) Glyceraldehyde-3-phosphate is then oxidized and converted to 1,3-bisphosphoglycerate by the enzyme Glyceraldehyde-3-phosphate dehydrogenase.

7) The enzyme phosphoglycerate kinase generates ATP by transferring a phosphate group from the 1,3-bisphosphoglycerate to ADP. The resulting products are 3-phosphoglycerate and ATP. This enzyme can also catalyze the reverse reaction.

8) Phosphoglycerate mutase(enzyme) shifts the phosphoric group from carbon three to carbon two, converting 3-phosphoglycerate to 2-phosphoglycerate.

9) Enolase catalyzes a dehydration reaction of 2-phosphoglycerate, producing phosphoenolpyruvate. Phosphoenolpyruvate allows the following reaction to occur with a higher delta G value, giving it stronger phosphoryl transferring ability.

10) Pyruvate kinase catalyzes the removal of the phosphoryl group from phosphoenolpyruvate, and adds this phosphoryl group to ADP, this results in the production of ATP and pyruvate.



Gluconeogenesis

Gluconeogenesis occurs in plants, animals and microorganisms. It is the conversion of pyruvate or lactate into glucose through a series of enzymatic reactions, resulting in glucose production. It occurs in the cytoplasm of cells. Many of the reactions involved in gluconeogenesis require magnesium as an enzyme cofactor. It is the organism's way of producing glucose from pyruvate and other small organic compounds. It occurs when glycogen stores are insufficient and the organism still requires energy such as during long periods without eating or after strenuous exercise. This process takes place in the liver, in the epithelial cells of the intestines, and in the renal medulla to some degree.

Lactic acid from anaerobic glycolysis is converted to glucose in the liver and sent back to the muscles(cori cycle). Several of the reactions in gluconeogenesis utilize the same enzymes as glycolysis, catalyzing the reaction in the opposite direction, but three enzyme catalyzed reactions are unique to gluconeogenesis.

Reactions unique to gluconeogenesis (the other steps are the reverse reactions of the glycolysis enzymes):

Conversion of pyruvate to phosphoenolpyruvate(PEP) occurs through a mechanism unique to gluconeogenesis and involves enzymes within the mitochondria and cytoplasm. There are two possible pathways, one which occurs mostly when alanine or pyruvate is the starting substrate, and another when lactate is the starting substrate.

1) Pyruvate carboxylase(this enzyme uses biotin as a coenzyme) converts pyruvate to oxaloacetate. Preceding this reaction, pyruvate is transferred into the mitochondria from the cytosol, the pyruvate carboxylase reaction takes place in the mitochondria. This reaction uses pyruvate HCO3- and ATP to produce oxaloacetate and ADP. If the starting substrate is alanine, a transamination reaction occurs within the mitochondria converting alanine to pyruvate. Malate dehydrogenase in the mitochondria then converts the oxaloacetate to malate, because only malate can be transported across its membrane(Oxaloacetate + NADH + H+ => Malate + NAD+). Once in the cytoplasm, it is reconverted to oxaloacetate(Malate + NAD+ => oxaloacetate + NADH + H+). Once in the cytoplasm, oxaloacetate is converted to PEP by phosphoenolpyruvate carboxykinase. If lactate is the precursor, it is converted to pyruvate by lactase dehydrogenase to begin the same reaction.

2) Fructose-1,6-bisphosphatase(FBP-1) catalyzes the production of fructose-6-phosphate from fructose-1,6-bisphophate through a hydrolysis reaction. This reaction is for the most part irreversible because it is very exergonic.

3) Glucose-6-phosphatase converts glucose-6-phosphate into glucose through a hydrolysis reaction(Glucose-6-phosphate + H2O => glucose + P). This enzyme exists in the liver, kidney, and epithelium of the small intestines.

Glycogen

Within living organisms, glucose is stored by the formation of long chains of glucose molecules. These long polysaccharides are called starch in plants, and glycogen in humans, they differ by the molecular bonding and branching patterns. In humans, glycogen is mostly stored in the muscle and liver cells. Glycogen stores within the muscle give the body a way to store energy that can be used if the body undergoes exercise or strenuous activity. Glycogen in the liver can be broken down into glucose and released into the blood stream where it can then supply tissues and organs with glucose if there is a deficient amount in the bloodstream.

Glycogen Metabolism

Glycogen phosphorylase cleaves the alpha 1-4 glycosidic bonds of glycogen, starting at the nonreducing end of the glycogen branch. This enzyme uses phosphate and attaches it to the leaving glucose molecule resulting in glucose-1-phosphate and the remaining glycogen branch. Pyridoxal phosphate is a cofactor for this reaction. Pyridoxal phosphate acts as an acid to promote phosphates attachment. This reaction occurs in the skeletal muscle and liver. Glycogen phosphorylase repeats this reaction until it is 4 glucose residues away from a branch point. In the intestines a different type of reaction occurs, with amylase catalyzing hydrolysis for the glycogen breakdown instead of phosphorolysis.

Oligo-glucan-transferase is the debranching enzyme that transfers the remaining branch of 4 glucose residues to the neighboring, longer glycogen chain, at which point the glycogen phosphorylase can continue to breakdown glycogen.

Phosphoglucomutase then converts the glucose-1-phosphate molecules into glucose-6-phosphate molecules, which can then undergo glycolysis. The liver contains glucose-6-phosphatase which can convert glucose-6-phosphate to glucose, which can then be released into the bloodstream.

Glycogen Synthesis

1) Phosphoglucomutase converts glucose-6-phosphate to glucose-1-phosphate. This reaction is reversible.

2) UDP-Glucose-pyrophosphorylase converts glucose-1-phosphate to UDP-glucose(Glucose-1-phosphate + UTP => UDP-glucose + Phosphate).

3) Glycogen synthase adds the glucose residue from the UDP-glucose to the non-reducing end of the glycogen chain. Glycogen synthase acts on a chain of 8 glucose residues, with the initial chain being formed by glycogenin. Glycogenin is an enzyme and a primer for glycogen synthesis which uses UDP-glucose molecules to form the initial chain of glucose residues.

4) Glycosyl transferase cleaves a portion of the glycogen chain (6-7 glucose residues long) and bonds the base of the cleaved chain to the C-6 of a glucose residue in or near the middle of the glycogen polymer, creating a branch.



Insulin

Insulin is released from the beta islet cells of the pancreas and acts on the receptors of muscle, liver and adipose tissue causing them to take glucose into the cells and convert it to glucose-6-phosphate. Insulin acts on liver cells, causing them to activate glycogen synthase, causing more glucose to be stored as glycogen. Insulin stimulates glycolysis resulting in Acetyl CoA production and can ultimately lead to glucose being turned into fat. Insulin causes more glucose to be stored as glycogen and as fat.



Sources:

1. Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. New York: W.H. Freeman, 2008. Print.

2. Brown, William Henry, Brent L. Iverson, Eric V. Anslyn, and Christopher S. Foote. Organic Chemistry. Australia: Cengage Learning, 2009. Print.

3. U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. December 2015. Available at http://health.gov/dietaryguidelines/2015/guidelines/.