L ASER G ODED

Carbohydrates are important macronutrients containing carbon, hydrogen and oxygen. They are commonly classified by their chemical characteristics based upon the Food and Agriculture Organization/World Health Organization Expert Consultation in 1997 (FAO/WHO, 1998). From these characteristics, carbohydrates can be divided into three groups: monosaccharides and disaccharides (sugars), oligosaccharides and polysaccharides (expressed in table one).

This classification however, provides some challenges, particularly in nutritional research as many of the chemically different carbohydrates present similarities in both physiology and health effects, thus rendering a chemical classification unsuitable at times (Mann, et al., 2007). Carbohydrates can therefore be classified in other ways. One such classification is distinguishing between digestible and non-digestible carbohydrates.

The Scientific Advisory Committee on Nutrition (2015), defines digestible carbohydrates as those that can be absorbed and digested in the small intestines whilst non-digestible carbohydrates are not digested in the small intestines (due to their resistant to hydrolysis) and make their way to the large intestines where their partial fermentation by bacteria occurs.

19 Table 1: Chemical classification of carbohydrates

Class Sub-group Components

Sugars Monosaccharides

Disaccharides

Glucose, Fructose, Galactose

Sucrose, Lactose, Maltose Oligosaccharides Malto-oligosaccharides Non-digestibles Maltodextrins Raffinose, Stachyose, Verbascose, Fructo-oligosaccharides Polysaccharides Starch Non-starch Polysaccharides Amylose, Amylopectin, Modified starches. Cellulose, Hemicellulose Pectin, Hydrocolloids (gum) Source: SACN (2015)

20 2.2.2: The Digestive System

2.2.2.1: Digestion

Globally, cereals such as corn, rice, wheat, starchy roots and legumes, supply the body with the large amounts of carbohydrates it requires (Brand-Miller, et al., 2008). Data from the National Diet and Nutrition Survey shows that in the United Kingdom, adults over the age of 65 receive most of their carbohydrates from bread (of note white bread), breakfast cereals, potato-based foods (chips, roasted, mashed) and fruit juices (Bates, et al., 2014).

In order for the human body to convert glucose to energy, carbohydrates must be broken down first through the process of digestion. Human digestion starts in the mouth. Complex carbohydrates such as starch and glycogen are broken down via the secretion of salivary a- amylase that targets internal a-1-4 glycosidic bonds within these nutrients specifically (Devlin, 2006). This process occurs during the chewing of the food and the movements of the tongue, rolling the hydrolysed food into a ball (bolus) which makes its way down the oesophagus to the stomach. In the stomach, salivary a-amylase is deactivated due to the stomach’s acidic nature. The enzyme can continue to function inside the bolus as long as it is not in contact with stomach acids (Binder and Rueben, 2009).

Complex carbohydrates (oligo, di, and polysaccharides) must be broken down into simple monosaccharides in order to be absorbed into the blood stream. This absorption occurs in the small intestines and only the monosaccharaides glucose and galactose can be actively absorbed via the sodium(Na+) dependent glucose transporter (SGLT1) during this process (Thoerens and Mueckler, 2010).

21 Pancreatic juices are secreted once the food reaches the lumen. These juices neutralise the gastric acid and contain pancreatic a-amylase. Whilst the digestion of starch polysaccharides begins via the secretion of salivary a-amylase, pancreatic a-amylase also targets a-1-4 glycosidic bonds and plays a more significant role in the digestive process breaking down complex carbohydrates even further, into simple carbohydrates (Binder and Rueben, 2009). The resulting products of the actions of pancreatic a-amylase are further acted upon by enzymes located on the plasma membranes of the brush borders of the intestinal epithelial cells. Where complex carbohydrates present resistant glycosidic bonds which cannot be broken down into monosaccharides by either pancreatic a-amylase or the brush border enzymes they are passed on to the large intestines where they are acted upon my specialised bacteria (Flint, et al., 2012).

2.2.2.2: Absorption

The carbohydrates which are broke down into monosaccharaides are then taken up by intestinal absorptive cells (enterocytes) via specialised protein transporters. SGLT1 aids in the active absorption of glucose as well as galactose. The glucose substrate , for example will bind itself to the transporter and take advantage of the high Na+ gradient outside the cell (this occurs due to the presence of Na+ K+ ATPases), allowing it to move from an area of high concentration of Na+ into the intracellular environment (lower Na+ concentration) (Binder and Reuben, 2009). Conversely, when the intracellular concentration of glucose is high, the glucose substrate can diffuse to lower concentrations outside the cell via diffusion transporters (GLUT2). These transporters are specific to different monosaccharaide substrates (glucose, galactose and fructose) they transport. Unlike glucose and galactose, which are aided by SGLT1 in active absorption, the diffusion transporter GLUT5 takes up fructose (Manolescu, et al., 2007).

22 The substrates of sugar (glucose, galactose and any remaining fructose) can now easily leave the cells pass across the concentration gradient into the adjacent blood supply of the intestinal epithelial cells with the aid of their diffusion transporters. Energy conversion can now occur. The processes of digestion and absorption are highlighted in the diagram below (Figure 1).

Figure 1: Diagram of the digestion and absorption of carbohydrates

23 2.2.3: Metabolism of Glucose

The metabolism of glucose involves different pathways. These pathways all have the common objective of producing energy for the body. The glycolytic pathway involves the breakdown of a glucose molecule into two pyruvate molecules and storing the energy released as ATP and NADPH (Nelson, et al., 2013). In instances where blood glucose levels are high, glycogen is synthesised to store glucose via the glycogenesis pathway and stored primarily in the liver. On the other hand, when glucose levels are low this glycogen is broken down into glucose via the process of glycogenolysis to reduce the glucose deficit (McKee and McKee, 2012). Non- carbohydrate molecules such as pyruvate, lactate, glycerol etc. can also be converted to glucose when the body’s glucose levels are diminished. This pathway is referred to as gluconeogenesis and is the inverse/ opposite of the glycolytic pathway (Maughan, 2008). The pentose phosphate pathway is another form of glucose metabolism that produces glucose through an alternative pathway (Nelson, et al., 2013).

2.2.3.1: The Glycolytic Pathway

Once glucose enters the blood stream it can be broken down to create energy. The glycolytic pathway is considered anaerobic as it does not require oxygen molecules to create energy and is the only method of energy production in some tissues (Nelson, et al., 2013). Glycolysis involves two stages. In stage one four steps occur causing glucose to form two molecules of glyceraldehyde-3-phosphate using up two ATP molecules in the process.

Firstly, glucose must be undergo phosphorylation to prevent its transport outside of the cell. ATP, hexokinase and Mg2+ are all necessary for this reaction. Once glucose has been phosphorylated and becomes glucose-6-phosphate, it is then converted to fructose-6- phosphate in a reaction which involves the enzyme phosphor-glucose isomerase.

24 Fructose-6-phosphate is then phosphorylated to become fructose-1, 6-bisphosphate. This reaction requires the presence of ATP, Mg2+ and PFK1 (phosphofructo-kinase1). Stage 1 then ends with the cleavage of fructose-1, 6-bisphosphate aided by the aldolase enzyme to create dihydroxyacetone phosphate and glyceralydehyde-3-phosphate.

Stage two of the glycolytic pathway is focused on the conversion of glyceralydehyde-3- phosphate into pyruvate producing four ATP and two NADPH molecules. In order to avoid the loss of glyceraldehyde-3-phosphate a reversible reaction occurs via the triose phosphate isomerase enzyme creating another glyceraldehyde-3-phosphate (G3P) from dihydroxyacetone phosphate. The original glucose molecule from stage one, is now converted to two molecules of G3P. G3P is then oxidised and phosphorylated creating glycerate-1, 3- biphosphate. The phosphoryl group of this product is then transferred to form glycerate-3- phosphate in the presence ADP, Mg2+ and phosphoglycerate kinase. This process also produces two ATP molecules. G3P is then interconverted to G2P, which is then dehydrated via the enzyme enolase to become phosphoenolpyruvate (PEP). Finally, to create pyruvate, the phosphoryl group of PEP is transferred via pyruvate kinase to ADP. Two molecules of ATP are thus formed from each glucose molecule. The entire glycolytic pathway is expressed in the illustration below in Figure 2.

25 Figure 2: Stage 1 (a) and stage 2(b) of the 10-step process of the Glycolytic Pathway.

26 Two important peptide hormones control the glycolytic process: glucagon and insulin. Both hormones are secreted by the pancreas and are responsible in ensuring that blood glucose levels remain stable. Healthy adult individuals present normal blood sugar levels between 4.0 to 5.4 mmol/L (72 to 99 mg/dL) when fasting (National Institute for Clinical Evidence, 2012). A detailed explanation of normal blood sugar levels in those with and without diabetes is given in table 2 below. Glucagon is released by the alpha cells of the pancreas when blood glucose levels (BGL) decrease while insulin, secreted by the beta cells of the same organ is released when blood glucose levels rise (McKee and McKee, 2012). In effect, increased secretion of glucagon inhibits all enzymes participating in glycogenesis while activating those in glycogenolysis. The opposite occurs in the presence of increased insulin secretion (Hall, 2015). A rise in blood glucose concentration levels however, is dependent on the rate of absorption, the rate of gastric emptying and, of interest to the author, the characteristics of the foods consumed (Scientific Advisory Committee on Nutrition, 2015).

Table 2: National Institute for Clinical Excellence (NICE) recommended target BGL

Target Levels by Type

Upon waking Before meals (pre-prandial)

At least 90 minutes after meals

(post prandial)

Non-diabetic* 4.0 to 5.4

mmol/L

under 7.8 mmol/L

Type 2 diabetes 4 to 7 mmol/L under 8.5 mmol/L

Type 1 diabetes 5 to 7 mmol/L 4 to 7 mmol/L 5 to 9 mmol/L

Children w/ type 1 diabetes

4 to 7 mmol/L 4 to 7 mmol/L 5 to 9 mmol/L