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Metabolism & Nutrition – Lecture 4: Carbohydrate metabolism

After the fat lectures today, the 4th lecture in the RuG Metabolism & Nutrition course was about carbodydrate metabolism.

Carbohydrate chemistry

Carbohydrates (CH₂O)m range from monosaccharides (glucose, fructose, galactose), and disaccharides (saccharose, lactose, maltose, isomaltose), through polysaccharides. Polysacharides are divided in α-glucosides (starch, glucogen) and β-glucosides (cellulose). Starch (plant-based) and glycogen (animal-based) are easily digestible. Cullulose is not digestible in the small intestine, and only marginally digestible in the colon.

Carbohydrate digestion & absorption

Most sugars are absorbed in the small intestine. Only monosaccharides are absorbed. Larger carbohydrates (disaccharides) have to be split first. Disaccharide bio-availability is high, but they have to be split first: lactose is split into galactose + glucose by lactase and saccharose is split into fructose + glucose by sucrase.

Starch (amylose/amylopectine polysacharides) is broken down into glucose monosaccharides.

Fructose is absorbed by GLUT5 transporter, glucose/galactose by SGLT1.

Glucose homeostatis

When you consume 100g sugar (400 calories), initially, you get some energy. Later (~40min), you get tired and lack of focus. During digestion, blood glucose rises rapidly (hyperglycemia). β-cells produce insulin, which prompt body cells to store glucose, leading to hypoglycemia. Glucagon triggers to conversion of glycogen back to glucose. By eating complex carbohydrate that are less easily digestible, the hypoglycemic dip following the hyperglycemic peak can be avoided.

Insulin stimulates anabolic pathways (storage, synthesis, etc.), so that proteins are synthesized.

Glucagon stimulates catabolic pathways (breakdown, energy production), so that proteins are broken down.

During fasting, blood glucose levels are kept within the 4–6mM range. After a meal, blood sugar can peak beyond 6mM, but it has to stay below 7.8mM.

  • Brain and nerve cells require glucose as fuel; they cannot oxidize fatty acids; they can oxidize ketone bodies (produced by the liver during long-term fasting, or while following an Atkinson-like diet) to produce glucose.
  • Red blood cells have no mitochondria and can only convert glucose into lactate for ATP production.
  • Liver cells (and kidney cells) synthesize glucose and secrete glucose in order to main blood [glucose] at ~5mM.
  • Liver cells synthesize ketone bodies when glucogen stores are insufficient. And excess of glucose is stored as glycogen and, if necessary, as fat. This fat is exported from the liver to the extrahepatic tissues as VLDL.
  • Muscle cells can oxidize glucose and fatty acids. Glucose absorption by muscle cells is prompted by insulin. Glycogen is synthesized from excess glucose.
  • Fat cells‘ glucose uptake is insulin-dependent. Much of this glucose is used for fat synthesis. Besides glucose, fatty acids can also be stored as fats, if they’re not oxidized as a direct energy source.

Insuline secretion

Insulin is secreted by beta-cells (50%) in Islands of Langerhans (3%) in pancreas. Pancreatic B-cells positively correlate insulin secretion to blood plasma [glucose]. This sensoring is done by glucokinase (in pancreas, liver and brain cells), which, to this end, has a very low KM (5.5 mmol/l). Hexokinase (other cells) has a much larger KM.

Carbohydrate metabolism

Glycogen → Glucose 1-phosphate → Glucose 6-phosphate

Fasting (low glucose): glucagon released by α-cells in the pancreas. Glucagon stimulates the conversion of glycogen to glucose. Adrenaline does the same.

Carbohydrate-related chronic disease

  • Bio-availability of lactose depends on lactase activity. This is high in babies, because mother’s milk contains 7% lactose. Lactase activity lowers between 3–7 years of age to 10% of initial activity. In lactose intolerant people, lactase activity seizes completely.
  • Galactosemia is a defect in the enzyme that converts galactose (one of the two monosaccharides produced by the breaksdown of lactose by lactase).
  • Tooth caries incidence and severity is hightened by amount and frequency of intake of ‘simple sugars’.

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