where'd the sugar go?

part ii

margie sanchez, science contributor

let's follow the sugars

    Remember that Jacob’s saliva begins to digest simple starch as soon as the cereal enters his mouth due to the presence of salivary amylase. This enzyme is only the first of many that the milk and cereal will encounter as we track and follow the glycolytic and gluconeogenic pathways in Jacob’s metabolism. Amylase splits starch into smaller polysaccharides. Then, further digestion continues in Jacob’s small intestine where pancreatic amylase completes the breakdown of starch into the disaccharide called maltose. This maltose generated from starch is hydrolyzed to glucose by the enzyme maltase in Jacob’s intestine. Maltase is one in a family of intestinal disaccharidases, each specific for a different disaccharide sugar.

   The lactose from the milk and the sucrose in the cereal are hydrolyzed by other members of this family of disaccharidases- lactase and sucrase. (Please note that lactose intolerance is due to the absence or insufficient levels of lactase.) The breakdown of lactose results in one molecule each of glucose and galactose. When sucrose is broken down it yields one molecule of glucose and one of fructose.  

     The glucose, fructose, and galactose molecules are now absorbed by Jacob’s intestine, through intestinal epithelial cells. The microvilli of these cells project into the lumen of Jacob’s intestine, thereby increasing the absorptive surface of each intestinal cell. Only two layers of cells separate the lumen from the blood in Jacob’s capillaries. Some sugars like fructose can freely move across the plasma membrane of an epithelial cell by facilitated diffusion since the concentration of these sugars is lower in capillary blood than in the intestinal lumen. However, glucose must be moved across by active transport due to its high concentration in Jacob’s blood.

     Fructose and galactose are transported by Jacob’s bloodstream to various tissues through Jacob’s body. These sugars are eventually absorbed by Jacob’s body cells and converted to intermediates in the glycolytic pathway. The pathway for galactose utilization is somewhat complex, requiring five reactions to convert galactose into glucose-6-phosphate. A genetic defect known as galactosemia prevents normal metabolism of galactose, resulting in high levels of galactose in the blood and high levels of galactose-1-phosphate in tissues. This disorder has serious consequences like mental retardation, but if the condition is diagnosed early in infancy, symptoms and problems can be eliminated by removing galactose sources like milk from the diet.

     Of course the main sugar in Jacob’s blood is glucose. After a meal like Jacob’s bowl of milk and cereal, in a few hours the concentration of glucose in Jacob’s blood will be about 80mg%, or 80 milligrams per 100 milliliters, or 4.4 m/M. The level could rise to 120mg% soon after Jacob has eaten but most of the time Jacob’s blood glucose level remains stable within a fairly narrow range. Maintaining blood glucose is one of the most important regulatory functions in Jacob’s body, especially for a healthy brain and nervous system. Jacob’s body is well equipped to regulate blood glucose by use of major regulatory hormones like insulin, glucagon, epinephrine, and norepinephrine.

   Once glucose enters Jacob’s bloodstream, it is transported to cells throughout his body. The glucose then encounters any one of four main outcomes:

·      It may be oxidized completely by aerobic respiration to CO₂

·      It may be fermented anaerobically to lactate

·      It may be synthesized into the polysaccharide glycogen

·      Or it may be converted to body fat

Aerobic respiration is the most common fate of glucose since most of the tissues in our bodies function aerobically, at least most of the time. Jacob’s brain in particular requires glucose because it is a most noteworthy aerobic organ, especially during tests or Fourth Grade spelling bees. In fact, Jacob’s brain requires large amounts of energy in order to maintain membrane potentials critical for rapid transmission of nerve impulses. His brain depends almost exclusively on glucose to meet those needs.  Indeed, Jacob’s brain utilizes about 120 grams of glucose every day. That accounts for approximately 15% of Jacob’s total energy consumption! At rest, the human brain uses about 60% of total glucose available and accounts for 20% of total oxygen consumption. Because the brain has no significant stores of glycogen, the supply of both oxygen and glucose to Jacob’s brain must be constant and steady. Even a short interruption or shortage can have serious consequences. Jacob’s heart has similar needs since it, too, is an aerobic organ with few energy reserves. Yet, unlike is brain, Jacob’s heart can use alternative fuel molecules such as lactate and fatty acids.

     The second outcome for glucose is its conversion to lactate. Glucose can be catabolized to lactate anaerobically as a consequence of fermentation, especially in red blood cells as well as skeletal muscle cells. Because red blood cells do not have mitochondria they must rely on glycolysis to meet their energy needs. Skeletal muscle functions with or without the presence of oxygen. During a soccer game, Jacob’s skeletal muscles work very hard and energy needs increase rapidly, thereby limiting oxygen. Therefore, glycolysis exceeds aerobic respiration, and several things occur:

·      Excess pyruvate is converted to lactate

·      Lactate then enters the bloodstream where it is….

·      Used for fuel in the heart and…

·      And used by gluconeogenic tissues, especially the liver

·      In the liver, lactate is reoxidized into pyruvate,

·      Then used to make glucose by gluconeogenesis

Glucose can now return to Jacob’s bloodstream where it can be used by skeletal muscle cells again. So, now Jacob can continue playing soccer with plenty of fuel to meet his body’s demand for increased energy requirements.

   Skeletal muscle is the primary source of blood lactate while the liver is the primary site of gluconeogenesis. Therefore a cycle is set up to balance the necessary pathways and reactions:

·      Glycolysis produces lactate under hypoxic (oxygen limited) muscle cells

·      Lactate is then transported from the muscle cells via the bloodstream to the liver

·      Gluconeogenesis occurs at the liver, converting lactate to glucose

·      Glucose is released into the blood

This process is called the Cori cycle, after Carl and Gerti Cori whose research in the 1930s and 1940s first described their observations. The next time you exert yourself, think about what is happening in your body as you are resting, attempting to “catch your breath”. Your muscle cells have just released lactate into your bloodstream, the lactate reaches your liver, and is then converted back into glucose. You are breathing hard so that your body uptakes as much oxygen as possible in order to return your body to aerobic conditions, to make ATP and GTP for gluconeogenesis in your liver, and to restore body glycogen levels.

    The third major fate for blood glucose is glycogen storage. Glycogen is stored mainly in the liver cells and skeletal muscle cells. Muscle glycogen is there to supply glucose during times of strenuous activity. On the other hand, liver glycogen is used as a source for glucose when the liver is cued by hormones to release glucose into the bloodstream to maintain the blood glucose level. Jacob probably won’t need this biochemical pathway when he plays video games, but it’s very useful when he sprints from third base and slides into home, or the catcher if he’s in Jacob’s way.

     The fourth possible fate of blood glucose is for synthesizing body fat.  For a trim, active little guy like Jacob this fourth outcome for glucose is a welcome one. But for some of us, well, let’s just say we really have to watch this last one. Like the initial phase of aerobic respiration, the pathway to fat is via pyruvate to acetyl CoA. When Jacob eats more food than his body needs for energy or for synthesizing other molecules, several steps occur to store that glucose as fat for later use:

·      First, excess glucose is oxidized to acetyl CoA

·      Acetyl CoA is then used to synthesize triacylglycerols

·      Triacylglycerol is stored as body fat, primarily in adipose (fat) tissue because it is specialized for that specific purpose

Therefore, Jacob’s body, like all humans, has three main sources of energy at all times for available use:

·      The glucose in the blood

·      The glycogen in liver and skeletal muscle cells

·      And the triacylglycerols in the adipose tissue

    

So, where did the sugar go after Jacob ate his milk and cereal? Jacob’s body engaged two major biochemical pathways to break down and store sugar for later use.  Glycolysis and gluconeogenesis are the two reverse reaction pathways that Jacob’s physiology utilized for the catabolism and anabolism of glucose. Glycolysis catabolizes, or breaks down glucose ultimately into pyruvate if oxygen is available. If oxygen is not available then glucose is ultimately converted to lactate and stored in red blood cells as well as skeletal muscle. Glucose can also be converted to glycogen and stored in liver and skeletal muscle cells, or triacylglycerol and stored in adipose tissue.  So then, when blood glucose levels run low, gluconeogenesis makes new glucose out of lactate, pyruvate, glycogen, or triacylglycerol. 

     All the glucose and other sugars in the body originate in the food we eat, either as monosaccharides already or from breaking down disaccharides and polysaccharides in the intestine. The major outcome for glucose is oxidation to CO₂ and water which we ultimately exhale and excrete. In the meantime, glucose circulates in the bloodstream or can be stored as glycogen in the liver and skeletal muscle, available for use as needed. Blood glucose is available for immediate use for oxidation by aerobic tissues like the brain. Glucose may be converted to lactate as part of the Cori cycle, or converted and stored for later use as glycogen or fat.

   Jacob likes milk and cereal. That’s a good thing because that bowl of cereal he’s eating for breakfast provides not just nutrients like calcium and Vitamin D, but fuel for his brain and muscles. All carbohydrates have the potential to provide energy to fuel our cells’ needs. The chemistry and the biochemical reactions required to catabolize and metabolize vary according to the size of each starch and sugar, but ultimately they can all be used to fuel the energy requirements of all the cells in our bodies. Just one caveat… most of us should really really try to avoid the conversion of excess glucose to fat. Remember the triacylglycerol conversion? Stored as fat in adipose tissue? Yeah, too much sugar really can make us FAT!