Tag Archives: carbohydrates

Cori cycle: definition, function, biochemistry, involved tissues

What is the Cori cycle?

The Cori cycle, or glucose-lactate cycle, was discovered by Carl Ferdinand Cori and Gerty Theresa Radnitz, a husband-and-wife team, in the ‘30s and ‘40s of the last century . They demonstrated the existence of a metabolic cooperation between the skeletal muscle working under low oxygen conditions and the liver. This cycle can be summarized as follows:

  • the conversion of glucose to lactic acid, or lactate, by anaerobic glycolysis in skeletal muscle cells;
  • the diffusion of lactate from muscle cells into the bloodstream, by which it is transported to the liver;
  • the conversion of lactate to glucose by hepatic gluconeogenesis;
  • the diffusion of glucose from the hepatocytes into the bloodstream, by which it is transported back to the skeletal muscle cells, thereby closing the cycle.

Summarizing, we have: part of the lactate produced in skeletal muscle is converted to glucose in the liver, and transported back to skeletal muscle, thus closing the cycle.

Glucose → Lactate →Glucose

The importance of this cycle is demonstrated by the fact that it may account for about 40% of plasma glucose turnover.

Where does the Cori cycle occur?

In addition to skeletal muscle, this metabolic cooperation was also demonstrated between other extrahepatic tissues and liver.  Indeed, like the glucose-alanine cycle, the glucose-lactate cycle is active between the liver and all those tissues that do not completely oxidize glucose to CO2 and H2O, in which case pyruvate for conversion to lactate or, by transamination, to alanine would lack (see below).
In addition to skeletal muscle cells, examples of cells that continually produce lactic acid are red blood cells, immune cells in the lymph nodules,  proliferating cells in the bone marrow, and epithelial cells in the skin.
Note: skeletal muscle produces lactate even at rest, although at low rate.

Cori Cycle
Fig. 1 – The Cori Cycle

From a biochemical point of view, the Cori cycle links gluconeogenesis with anaerobic glycolysis, using different tissues to compartmentalize opposing metabolic pathways. In fact, in the same cell, regardless of the cell type, these metabolic pathways are not very active simultaneously. Glycolysis is more active when the cell requires ATP; by contrast, when the demand for ATP is low, gluconeogenesis, in those cells where it occurs, is more active.
And it is noteworthy that, although traditionally the metabolic pathways, such as glycolysis, citric acid cycle, or gluconeogenesis, are considered to be confined within individual cells, the Cori cycle, as well as the glucose-alanine cycle, occurs between different cell types.
Finally, it should be underscored that the Cori cycle also involves the renal cortex, particularly the proximal tubules, another site where gluconeogenesis occurs.

The steps of the Cori cycle

The analysis of the steps of the Cori cycle is made considering the lactate produced by red blood cells and skeletal muscle cells.
Mature red blood cells are devoid of mitochondria, nucleus and ribosomes, and obtain the necessary energy only by glycolysis. The availability of NAD+ is essential for glycolysis to proceed as well as for its rate: the oxidized form of the coenzyme is required for the oxidation of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate in the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12).

Glyceraldehyde 3-phosphate + NAD+ → 1,3-Bisphosphoglycerate + NADH + H+

The accumulation of NADH is avoided by the reduction of pyruvate to lactate, in the reaction catalyzed by lactate dehydrogenase (EC 1.1.1.27), where NADH acts as reducing agent.

Pyruvate + NADH + H+ → Lactate + NAD+

The skeletal muscle, particularly fast-twitch fibers which contain a reduced number of mitochondria, under low oxygen condition, such as during intense exercise, produces significant amounts of lactate. In fact, in such conditions:

  • the rate of pyruvate production by glycolysis  exceeds the rate of its oxidation by the citric acid cycle, so that less than 10% of the pyruvate enters the citric acid cycle;
  • the rate at which oxygen is taken up by the cells is not sufficient to allow aerobic oxidation of all the NADH  produced.

And, like in red blood cells, the reaction catalyzed by lactate dehydrogenase, regenerating NAD+, allows glycolysis to proceed.
However, lactate is an end product of metabolism that must be converted back into pyruvate to be used.
The plasma membrane of most cells is freely permeable to both pyruvate and lactate that can thus reach the bloodstream. And, regarding for example the skeletal muscle, the amount of lactate that leaves the cell is greater than that of pyruvate due to the high NADH/NAD+ ratio in the cytosol and to the catalytic properties of the skeletal muscle isoenzyme of LDH.
Once into the bloodstream, lactate reaches the liver, which is its major user, where it is oxidized to pyruvate in the reaction catalyzed by the liver isoenzyme of lactate dehydrogenase (see below).

Lactate + NAD+ → Pyruvate + NADH + H+

In the hepatocyte, this oxidation is favored by the low NADH/NAD+ ratio in the cytosol.
Then, pyruvate enters the gluconeogenesis pathway to be converted into glucose.
Glucose leaves the liver, enters into the bloodstream and is delivered to the muscle, as well as to other tissues and cells that require it, such as red blood cells and neurons, thus closing the cycle.

Lactate dehydrogenase

The enzyme is a tetramer composed of two different types of subunits, designed as:

  • H subunit (heart) or B chain;
  • M subunit (muscle) or A chain.

The H subunit predominates in the heart, whereas the M subunit predominates in the  skeletal muscle and liver. Typically, tissues in which a predominantly or exclusively aerobic metabolism occurs, such as the heart, synthesize H subunits to a greater extent than M subunits, whereas tissues in which anaerobic metabolism is important, such as skeletal muscle, synthesize M subunits to a greater extent than H subunits.
The two subunits associate in 5 different ways to form homopolymers, that is, macromolecules formed by repeated, identical subunits, or heteropolymers, that is, macromolecules formed by different subunits. Different LDH  isoenzymes have different catalytic properties, as well as different distribution in various tissues, as indicated below:

  • H4, also called type 1, LDH1, or A4, a homopolymer of H subunits, is found in cardiac muscle, kidney, and red blood cells;
  • H3M1, also called type 2, LDH2, or A3B, has a tissue distribution similar to that of LDH1;
  • H2M2, also called type 3, LDH3, or A2B2, is found in the spleen, brain, white cells, kidney, and lung;
  • H1M3, also called type 4, LDH4, or AB3, is found in the spleen, lung, skeletal muscle, lung, red blood cells, and kidney;
  • M4, also called type 5, LDH5, or B4, a homopolymer of M subunits, is found in the liver, skeletal muscle, and spleen.

The H4 isoenzyme has a higher substrate affinity than the M4 isoenzyme.
The H4 isoenzyme is allosterically inhibited by high levels of pyruvate (its product), whereas the M4 isoenzyme is not.
The other LDH isoenzymes have intermediate properties, depending on the ratio between the two types of subunits.
It is thought that the H4 isoenzyme is the most suitable for catalyzing the oxidation of lactate to pyruvate that, in the heart, due to its exclusively aerobic metabolism, is then completely oxidized to CO2 and H2O. Instead, the M4 isoenzyme is the main isoenzyme found in skeletal muscle, most suitable for catalyzing the reduction of pyruvate to lactate, thus allowing glycolysis to proceed in anaerobic conditions.

Other metabolic fates of lactate

From the above, it is clear that lactate is not a metabolic dead end, a waste product of glucose metabolism.
And it may have a different fate from that entering the Cori cycle.
For example, in skeletal muscle during recovery following an exhaustive exercise, that is, when oxygen is again available, or if the exercise is of low intensity, lactate is re-oxidized to pyruvate, due to NAD+ availability, and then completely oxidized to CO2 and H20, with a greater production of ATP than in anaerobic condition. In such conditions, the energy stored in NADH will be released, yielding on average 2.5 ATP per molecule of NADH.
In addition, lactate can be taken up by exclusively aerobic tissues, such as heart, to be oxidized to CO2 and H20.

Energy cost of the Cori cycle

The Cori cycle results in a net consumption of 4 ATP.
The gluconeogenic leg of the cycle consumes 2 GTP and 4 ATP per molecule of glucose synthesized, that is, 6 ATP.
The ATP-consuming reactions are catalyzed by:

  • pyruvate carboxylase (EC 6.4.1.1): an ATP;
  • phosphoenolpyruvate carboxykinase (EC 4.1.1.32): a GTP;
  • glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12): an ATP.

Since two molecules of lactate are required for the synthesis of one molecule of glucose, the net cost is 2×3=6 high energy bonds per molecule of glucose.
Conversely, the glycolytic leg of the cycle produces only 2 ATP per molecule of glucose.
Therefore, more energy is required to produce glucose from lactate than that obtained by anaerobic glycolysis in extrahepatic tissues. This explains why the Cori cycle cannot be sustained indefinitely.

Is the Cori cycle a futile cycle?

The continuous breakdown and resynthesis of glucose, feature of the Cori cycle, might seem like a waste of energy. Indeed, this cycle allows the effective functioning of many extrahepatic cells at the expense of the liver and partly of the renal cortex. Below, two examples.

  • Red blood cells
    These cells, lacking a nucleus, ribosomes, and mitochondria, are smaller than most other cells. Their small size allows them to pass through tiny capillaries. However, the lack of mitochondria makes them completely dependent on anaerobic glycolysis for ATP production. Then, the lactate is partly disposed of by the liver and renal cortex.
  • Skeletal muscle
    Its cells, and particularly fast-twitch fibers contracting under low oxygen conditions, such as during intense exercise, produce much lactate.
    In such conditions, anaerobic glycolysis leads to the production of 2 ATP per molecule of glucose, 3 if the glucose comes from muscle glycogen, therefore, much lower than the 29-30 ATP produced by the complete oxidation of the monosaccharide. However, the rate of ATP production by anaerobic glycolysis is greater than that produced by the complete oxidation of glucose. Therefore, to meet the energy requirements of contracting muscle, anaerobic glycolysis is an effective means of ATP production. But this could lead to an intracellular accumulation of lactate, and a consequent reduction in intracellular pH. Obviously, such accumulation does not occur, due also to the Cori cycle, in which the liver pays the cost of the disposal of a large part of the muscle lactate, thereby allowing the muscle to use ATP for the contraction.
    And the oxygen debt, which always occurs after a strenuous exercise, is largely due to the increased oxygen demand of the hepatocytes, in which the oxidation of fatty acids, their main fuel, provides the ATP required for gluconeogenesis from lactate.
  • During trauma, sepsis, burns, or after major surgery, an intense cell proliferation occurs in the wound, that is a hypoxic tissue, and in bone marrow. This in turn results in greater production of lactate, an increase in the flux through the Cori cycle and an increase in ATP consumption in the liver, which, as previously said, is supported by an increase in fatty acid oxidation. Hence, the nutrition plan provided to these patients must be taken into account this increase in energy consumption.
  • A similar condition seems to occur also in cancer patients with progressive weight loss.
  • The Cori cycle is also important during overnight fasting and starvation.

The Cori cycle and glucose-alanine cycle

These cycles are metabolic pathways that contribute to ensure a continuous delivery of glucose to tissues for which the monosaccharide is  the primary source of energy.
The main difference between the two cycles consists in the three carbon intermediate which is recycled: in the Cori cycle, carbon returns to the liver in the form of pyruvate, whereas in the glucose-alanine cycle in the form of alanine.
For more information, see: glucose-alanine cycle.

References

Bender D.A. Introduction to nutrition and metabolism. 3rd Edition. Taylor & Francis, 2004

Berg J.M., Tymoczko J.L., and Stryer L. Biochemistry. 5th Edition. W. H. Freeman and Company, 2002

Iqbal S.A., Mido Y. Biochemistry. Discovery Publishing House, 2005 [Google eBook]

Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 6th Edition. W.H. Freeman and Company, 2012

Newsholme E.A., Leech T.R. Functional biochemistry in health and disease. John Wiley J. & Sons, Inc., Publication, 2010 [Google eBook]

Rawn J.D. Biochimica. Mc Graw-Hill, Neil Patterson Publishers, 1990

Rosenthal M.D., Glew R.H. Medical biochemistry – Human metabolism in health and disease. John Wiley J. & Sons, Inc., Publication, 2009

Shils M.E., Olson J.A., Shike M., Ross A.C. Modern nutrition in health and disease. 9th Ed., by Lippincott, Williams & Wilkins, 1999

Stipanuk M.H., Caudill M.A. Biochemical, physiological, and molecular aspects of human nutrition. 3rd Edition. Elsevier health sciences, 2013 [Google eBooks]

Gluten: definition, structure, properties, wheat, cereal list

What is gluten?

Gluten
Fig. 1 – Wheat

Gluten is not a single protein but a mixture of cereal proteins, about 80% of its dry weight (for example gliadins and glutenins in wheat grains), lipids, 5-7%, starch, 5-10%, water, 5-8%, and mineral substances, <2%.
It forms when components naturally present in the grain of cereals, the caryopsis, and in their flours, are joined together by means of mechanical stress in aqueous environment, i.e. during the formation of the dough.
The term is also related to the family of proteins that cause problems for celiac patients (see below).
Isolated for the first time in 1745 from wheat flour by the Italian chemist Jacopo Bartolomeo Beccari, it can be extracted from the dough by washing it gently under running water: starch, albumins and globulins, that are water-soluble, are washed out, and a sticky and elastic mass remains, precisely the gluten (it means glue in Latin).

Cereals containing gluten

It is present in:

  • wheat, such as:

durum wheat (Triticum durum); groats and semolina for dry pasta making are obtained from it;
common wheat or bread wheat (Triticum aestivum), so called because it is used in bread and fresh pasta making, and in bakery products;

  • rye (Secale cereale);
  • barley (Hordeum vulgare);
  • spelt, in the three species:

einkorn (Triticun monococcum);
emmer (Triticum dicoccum Schrank);
spelta (Triticum spelta);

  • khorasan wheat (Triticum turanicum); a variety of it is Kamut®;
  • triticale (× Triticosecale Wittmack), which is a hybrid of rye and common wheat;
  • bulgur, which is whole durum wheat, sprouted and then processed;
  • seitan, which is not a cereal, but a wheat derivative, also defined by some as “gluten steak”.

Given that most of the dietary intake of gluten comes from wheat flour, of which about 700 million tons per year are harvested, representing about 30% of the global cereal production, the following discussion will focus on wheat gluten, and mainly on its proteins.

Note: the term gluten is also used to indicate the protein fraction that remains after removal of starch and soluble proteins from the dough obtained with corn flour: however, this “corn gluten” is “functionally” different from that obtained from wheat flour.

Cereal grain proteins

Gluten
Fig. 2 – Cereal Grain Proteins

The study of cereal grain proteins, as seen, began with the work of Beccari. 150 years later, in 1924, the English chemist Osborne T.B., which can rightly be considered the father of plant protein chemistry, developed a classification based on their solubility in various solvents.
The classification, still in use today, divides plant proteins into 4 families.

  • Albumins, soluble in water.
  • Globulins, soluble in saline solutions; for example avenalin of oat.
  • Prolamins, soluble in 70% alcohol solution, but not in water or absolute alcohol.
    They include:

gliadins of wheat;
zein of corn;
avenin of oats;
hordein of barley;
secalin of rye.

They are the toxic fraction of gluten for celiac patients.

  • Glutelins, insoluble in water and neutral salt solutions, but soluble in acidic and basic solutions.
    They include glutenins of wheat.

Albumins and globulins are cytoplasmic proteins, often enzymes, rich in essential amino acids, such as lysine, tryptophan and methionine. They are found in the aleurone layer and embryo of the caryopsis.
Prolamins and glutelins are the storage proteins of cereal grains. They are rich in glutamine and proline, but very low in lysine, tryptophan and methionine. They are found in the endosperm, and are the vast majority of the proteins in the grains of wheat, corn, barley, oat, and rye.
Although Osborne classification is still widely used, it would be more appropriate to divide cereal grain proteins into three groups: structural and metabolic proteins, storage proteins, and defense proteins.

Wheat gluten proteins

Proteins represent 10-14% of the weight of the wheat caryopsis (about 80% of its weight consists of carbohydrates).
According to the Osborne classification, albumins and globulins represent 15-20% of the proteins, while prolamins and glutelins are the remaining 80-85%, composed respectively of gliadins, 30-40%, and glutenins, 40-50%. Therefore, and unlike prolamins and glutelins in the grains of other cereals, gliadins and glutenins are present in similar amounts, about 40%.
Technologically, gliadins and glutenins are very important. Why?
These proteins are insoluble in water, and in the dough, that contains water, they bind to each other through a combination of intermolecular bonds, such as:

  • covalent bonds, i.e. disulfide bridges;
  • noncovalent bonds, such as hydrophobic interactions, van der Waals forces, hydrogen bonds, and ionic bonds.

Thanks to the formation of these intermolecular bonds, a three-dimensional lattice is formed. This structure entraps starch granules and carbon dioxide bubbles produced during leavening, and gives strength and elasticity to the dough, two properties of gluten widely exploited industrially.
In the usual diet of the European adult population, and in particular in Italian diet that is very rich in derivatives of wheat flour, gliadin and glutenin are the most abundant proteins, about 15 g per day. What does this mean? It means that gluten-free diet engages celiac patients both from a psychological and social point of view.

Note: the lipids of the gluten are strongly associated with the hydrophobic regions of gliadins and glutenins and, unlike what you can do with the flour, they are extracted with more difficulty (the lipid content of the gluten depends on the lipid content of the flour from which it was obtained).

Gliadins: extensibility and viscosity

Gluten
Fig. 3 – Wheat Grain Proteins

Gliadins are hydrophobic monomeric prolamins, of globular nature and with low molecular weight. On the basis of electrophoretic mobility in low pH conditions, they are separated into the following types:

  • alpha/beta, and gamma, rich in sulfur, containing cysteines, that are involved in the formation of intramolecular disulfide bonds, and methionines;
  • omega, low in sulfur, given the almost total absence of cysteine and methionine.

They have a low nutritional value and are toxic to celiac patients because of the presence of particular amino acid sequences in the primary structure, such as proline-serine-glutamine-glutamine and glutamine-glutamine-glutamine-proline.
Gliadins are associated with each other and with glutenins through noncovalent interactions; thanks to that, they act as “plasticizers” in dough making. Indeed, they are responsible for viscosity and extensibility of gluten, whose three-dimensional lattice can deform, allowing the increase in volume of the dough as a result of gas production during leavening. This property is important in bread-making.
Their excess leads to the formation of a very extensible dough.

Glutenins: elasticity and toughness

Glutenins are polymeric proteins, that is, formed of multiple subunits, of fibrous nature, linked together by intermolecular disulfide bonds. The reduction of these bonds allows to divide them, by SDS-PAGE, into two groups.

  • High molecular weight (HMW) subunits, low in sulfur, that account for about 12% of total gluten proteins. The noncovalent bonds between them are responsible for the elasticity and tenacity of the gluten protein network, that is, of the viscoelastic properties of gluten, and so of the dough.
  • Low molecular weight (LMW) subunits, rich in sulfur (cysteine residues).
    These proteins form intermolecular disulfide bridges to each other and with HMW subunits, leading to the formation of a glutenin macropolymer.

Glutenins allow dough to hold its shape during mechanical (kneading) and not mechanical stresses (increase in volume due to both the leavening and the heat of cooking that increases the volume occupied by gases present) which is submitted. This property is important in pasta making.
If in excess, glutenins lead to the formation of a strong and rigid dough.

Properties of wheat gluten

From the nutritional point of view, gluten proteins do not have a high biological value, being low in lysine, an essential amino acid. Therefore, a gluten-free diet does not cause any important nutritional deficiencies.
On the other hand, it is of great importance in food industry: the combination, in aqueous solution, of gliadins and glutenins to form a three-dimensional lattice, provides viscoelastic properties, that is, extensibility-viscosity and elasticity-tenacity, to the dough, and then, a good structure to bread, pasta, and in general, to all foods made with wheat flour.
It has a high degree of palatability.
It has a high fermenting power in the small intestine.
It is an exorphin: some peptides produced from intestinal digestion of gluten proteins may have an effect in central nervous system.

Gluten-free cereals

The following is a list of gluten-free cereals, minor cereals, and pseudocereals used as foods.

  • Cereals

corn or maize (Zea mays)
rice (Oryza sativa)

  • Minor cereals
    They are defined “minor” not because they have a low nutritional value, but because they are grown in small areas and in lower quantities than wheat, rice and maize.

Fonio (Digitaria exilis)
Millet (Panicum miliaceum)
Panic (Panicum italicum)
Sorghum (Sorghum vulgare)
Teff (Eragrostis tef)
Teosinte; it is a group of four species of the genus Zea. They are plants that grow in Mexico (Sierra Madre), Guatemala and Venezuela.

  • Pseudocereals.
    They are so called because they combine in their botany and nutritional properties characteristics of cereals and legumes, therefore of another plant family.

Amaranth; the most common species are:

Amaranthus caudatus;
Amaranthus cruentus;
Amarantus hypochondriacus.

Buckwheat (Fagopyrum esculentum)
Quinoa (Chenopodium quinoa), a pseudocereal with excellent nutritional properties, containing fibers, iron, zinc and magnesium. It belongs to Chenopodiaceae family, such as beets.

  • Cassava, also known as tapioca, manioc, or yuca (Manihot useful). It is grown mainly in the south of the Sahara and South America. It is an edible root tuber from which tapioca starch is extracted.

It should be noted that naturally gluten-free foods may not be truly gluten-free after processing. Indeed, the use of derivatives of gliadins in processed foods, or contamination in the production chain may occur, and this is obviously important because even traces of gluten are harmful for celiac patients.

Oats and gluten

Oats (Avena sativa) is among the cereals that celiac patients can eat. Recent studies have shown that it is tolerated by celiac patients, adult and child, even in subjects with dermatitis herpetiformis. Obviously, oats must be certified as gluten-free (from contamination).

References

Beccari J.B. De Frumento. De bononiensi scientiarum et artium instituto atque Academia Commentarii, II. 1745:Part I.,122-127

Bender D.A. “Benders’ dictionary of nutrition and food technology”. 8th Edition. Woodhead Publishing. Oxford, 2006

Berdanier C.D., Dwyer J., Feldman E.B. Handbook of nutrition and food. 2th Edition. CRC Press. Taylor & Francis Group, 2007

Phillips G.O., Williams P.A. Handbook of food proteins. 1th Edition. Woodhead Publishing, 2011

Shewry P.R. and Halford N.G. Cereal seed storage proteins: structures, properties and role in grain utilization. J Exp Bot 2002:53(370);947-958 [Abstract]

Yildiz F. Advances in food biochemistry. CRC Press, 2009

Digestion of starch and alpha-amylase

Factors affecting relationship between starch and alpha-amylase

alpha-amylase
Fig. 1 – Spaghetti

Amylose and amylopectin, the two families of homopolysaccharides constituting starch, during their biosynthesis within vegetable cells, are deposited in highly organized particles called granules.
Granules have a partially crystalline structure and diameter ranging from 3 to 300 µm.
The access of the alpha-amylase, the enzyme that catalyzes the breakdown of amylose and amylopectin into maltose, maltotriose, and alpha-dextrins or alpha-limit dextrins, to carbohydrates making up granules varies as a function of:

  • amylose-amylopectin ratio;
  • temperature and packaging of amylose and amylopectin;
  • granules-associated proteins;
  • presence of fibers.

Amylose-amylopectin ratio

Starch for foodstuff use is obtained from various sources, the most important of which are corn (normal, waxy or high amylose content), potatoes, rice, tapioca and wheat.
Depending on botanical origin, molecular weight, degree of branching, and amylose-amylopectin ratio will vary.
Generally, there is 20-30% amylose and 70-80% amylopectin, even if there are starches with high amylose or amylopectin content (e.g. waxy corn). These differences justify the existence of starches with different chemical-physical characteristics and, to a certain extent, different digestibility.

  • corn: 24% amylose, 76% amylopectin;
  • waxy corn: 0,8% amylose, 99.2% amylopectin;
  • Hylon VII corn: 70% amylose, 30% amylopectin;
  • potatoes: 20% amylose, 80% amylopectin;
  • rice: 18.5 amylose, 81.5% amylopectin;
  • tapioca: 16.7% amylose, 83.3% amylopectin;
  • wheat: 25% amylose, 75% amylopectin.

Temperature and packaging of amylose and amylopectin

The chains of amylose, and to a lesser extent ramifications of amylopectin, thanks to the formation of hydrogen bonds with neighboring molecules and within the same molecules, have the tendency to aggregate. For this reason, pure amylose and amylopectin are poorly soluble in water at below 55 °C (131°F), and are more resistant to alpha-amylase action (resistant starch).
However, in aqueous solution, these granules hydrate increasing in volume of about 10%.
Above 55°C (131°F), the partially crystalline structure is lost, granules absorb further water, swell and pass to a disorganized structure, that is, starch gelatinization occurs, by which starch assumes an amorphous structure more easily attachable by alpha-amylase.

Granules-associated proteins

In granules, starch is present in association with proteins, many of which are hydrophobic, that means with low affinity for water. This association have the effect to hinder the interaction, in the intestinal lumen, between alpha-amylase, a polar protein, and the polysaccharides making up starch granules.
The physical processes to which cereals undergo before being eaten, such as milling or heating for several minutes, change the relationship between starch and the associated proteins, making it more available to α-amylase action.

Fibers

Alpha-amylase activity may also be hindered by the presence of nondigestible polysaccharides, the fibers: cellulose, hemicellulose and pectin.

Conclusions

The presence of inhibitors, of both chemical and physical type, hinders starch digestion, even when pancreatic α-amylase secretion is normal. This means that a part of starch, ranging from 1% to 10%, may escape the action of the enzyme, being then metabolized by colonic bacteria.
Refined starch is instead hydrolyzed efficiently, even when there is an exocrine pancreatic insufficiency (EPI), condition in which alpha-amylase concentration in gut lumen may be reduced to 10% of the normal.

References

Arienti G. “Le basi molecolari della nutrizione”. Seconda edizione. Piccin, 2003

Belitz .H.-D., Grosch W., Schieberle P. “Food Chemistry” 4th ed. Springer, 2009

Bender D.A. “Benders’ Dictionary of Nutrition and Food Technology”. 8th Edition. Woodhead Publishing. Oxford, 2006

Cozzani I. and Dainese E. “Biochimica degli alimenti e della nutrizione”. Piccin Editore, 2006

Giampietro M. “L’alimentazione per l’esercizio fisico e lo sport”. Il Pensiero Scientifico Editore, 2005

Mahan LK, Escott-Stump S.: “Krause’s foods, nutrition, and diet therapy” 10th ed. 2000

Mariani Costantini A., Cannella C., Tomassi G. “Fondamenti di nutrizione umana”. 1th ed. Il Pensiero Scientifico Editore, 1999

Osorio-Dıaz P., Bello-Perez L.A., Agama-Acevedo E., Vargas-Torres A., Tovar J., Paredes-Lopez O. In vitro digestibility and resistant starch content of some industrialized commercial beans (Phaseolus vulgaris L.). Food Chem 2002;78:333-7 [Abstract]

Shils M.E., Olson J.A., Shike M., Ross A.C. “Modern nutrition in health and disease” 9th ed., by Lippincott, Williams & Wilkins, 1999

Stipanuk M.H.. “Biochemical and physiological aspects of human nutrition” W.B. Saunders Company-An imprint of Elsevier Science, 2000

Maltodextrin, fructose and endurance sports

Carbohydrate ingestion can improve endurance capacity and performance.
The ingestion of different types of carbohydrates, which use different intestinal transporters, can:

  • increase total carbohydrate absorption;
  • increase exogenous carbohydrate oxidation;
  • and therefore improve performance.

Glucose and fructose

When a mixture of glucose and fructose is ingested (in the analyzed literature, respectively 1.2 and 0.6 g/min, ratio 2:1, for total carbohydrate intake rate to 1.8 g/min), there is less competition for intestinal absorption compared with the ingestion of an iso-energetic amount of glucose or fructose,  two different intestinal transporters being involved. Furthermore, fructose absorption is stimulated by the presence of glucose.

This can:

The combined ingestion of glucose and fructose allows to obtain exogenous carbohydrate oxidation rate around 1,26 g/min, therefore, higher than the rate reported with glucose alone (1g/min), also in high concentration.
The observed difference (+0,26 g/min) can be fully attributed to the oxidation of ingested fructose.

Sucrose and glucose

The ingestion of sucrose and glucose, in the same conditions of the ingestion of glucose and fructose (therefore, respectively 1.2 and 0.6 g/min, ratio 2:1, for total carbohydrate intake rate to 1.8 g/min), gives similar results.

Glucose, sucrose and fructose

Very high oxidation rates are found with a mixture of glucose, sucrose, and fructose (in the analyzed literature, respectively 1.2, 0.6 and 0.6 g/min, ratio 2:1:1, for total carbohydrate intake rate to 2.4 g/min; however, note the higher amounts of ingested carbohydrates).

Maltodextrin and fructose

Maltodextrin and Fructose: Oxidation of Ingested Carbohydrates
Fig. 1 – Oxidation of Ingested Carbohydrates

High oxidation rates are also observed with combinations of maltodextrin and fructose, in the same conditions of the ingestion of glucose plus fructose (therefore, respectively 1.2 and 0.6 g/min, ratio 2:1, for total carbohydrate intake rate to 1.8 g/min).

Such high oxidation rates can be achieved with carbohydrates ingested in a beverage, in a gel or in a low-fat, low protein, low-fiber energy bar.

The best combination of carbohydrates ingested during exercise seems to be the mixture of maltodextrin and fructose in a 2:1 ratio, in a 5% solution, and in a dose around 80-90 g/h.
Why?

  • This mixture has the best ratio between amount of ingested carbohydrates and their oxidation rate and it means that smaller amounts of carbohydrates remain in the stomach or gut reducing the risk of gastrointestinal complication/discomfort during prolonged exercise (see brackets grafa in the figure).
  • A solution containing a combination of multiple transportable carbohydrates and a carbohydrate content not exceeding 5% optimizes gastric emptying rate and improves fluid delivery.

Example of a 5% carbohydrate solution containing around 80-90 g of maltodextrin and fructose in a 2:1 rate; ingestion time around 1 h.

Conclusion

During prolonged exercise, when high exogenous carbohydrate oxidation rates are needed, the ingestion of multiple transportable carbohydrates is preferred above that of large amounts of a single carbohydrate.
The best mixture seems to be maltodextrin and fructose, in a 2:1 ratio, in a 5% concentration solution, and at ingestion rate of around 80-90 g/h.

References

Prolonged exercise and carbohydrate ingestion

Prolonged Exercise: Open Water Swimming
Fig. 1 – Open Water Swimming

During prolonged exercise (>90 min), like marathon, Ironman, cross-country skiing, road cycling or open water swimming, the effects of supplementary carbohydrates on performance are mainly metabolic rather than central and include:

  • the provision of an additional muscle fuel source when glycogen stores become depleted;
  • muscle glycogen sparing;
  • the prevention of low blood glucose concentrations.

How many carbohydrates should an athlete take?

The optimal amount of ingested carbohydrate is that which results in the maximal rate of exogenous carbohydrate oxidation without causing gastrointestinal discomfort”. (Jeukendrup A.E., 2008).

Prolonged exercise: which carbohydrates should an athlete take?

Until 2004 it was believed that carbohydrates ingested during exercise (also prolonged exercise) could be oxidized at a rate no higher than 1 g/min, that is, 60 g/h, independent of the type of carbohydrate.
Exogenous carbohydrate oxidation is limited by their intestinal absorption and the ingestion of more than around 60 g/min of a single type of carbohydrate will not increase carbohydrate oxidation rate but it is likely to be associated with gastrointestinal discomfort (see later).
Why?
At intestinal level, the passage of glucose (and galactose) is mediated by a sodium dependent transporter called SGLT1. This transporter becomes saturated at a carbohydrate intake about 60 g/h and this (and/or glucose disposal by the liver that regulates its transport into the bloodstream) limits the oxidation rate to 1g/min or 60 g/h. For this reason, also when glucose is ingested at very high rate (>60 g/h), exogenous carbohydrate oxidation rates higher 1.0-1.1 g/min are not observed.

The rate of oxidation of ingested maltose, sucrose, maltodextrins and glucose polymer is fairly similar to that of ingested glucose.

Fructose uses a different sodium independent transporter called GLUT5. Compared with glucose, fructose has, like galactose, a lower oxidation rate, probably due to its lower rate of intestinal absorption and the need to be converted into glucose in the liver, again like galactose, before it can be oxidized.

Prolonged Exercise: Maltodextrin and Fructose: Oxidation of Ingested Carbohydrates
Fig. 1 – Oxidation of Ingested Carbohydrates

However, if the athlete ingests different types of carbohydrates, which use different intestinal transporters, exogenous carbohydrate oxidation rate can increase significantly.
It seems that the best mixture is maltodextrins and fructose.

Note: the high rates of carbohydrate ingestion may be associated with delayed gastric emptying and fluid absorption; this can be minimized by ingesting combinations of multiple transportable carbohydrates that enhance fluid delivery compared with a single carbohydrate. This also causes relatively little gastrointestinal distress.

Conclusion

The ingestion of different types of carbohydrates that use different intestinal transporters can:

References

Carbohydrate ingestion during exercise of relatively short duration and high intensity

Intermittent high intensity exercise and carbohydrate ingestion

High Intensity: During-Exercise Nutrition
Fig. 1- During-Exercise Nutrition

Carbohydrate ingestion during intermittent high intensity or prolonged (>90 min) sub-maximal exercise can:

  • increase exercise capacity;
  • improve exercise performance;
  • postpone fatigue.

The intake of very small amounts of carbohydrates or carbohydrate mouth rinsing (for example with a 6% maltodextrin solution) may improve exercise performance by 2-3% when the exercise is of relatively short duration (<1 h) and high intensity (>75% VO2max), that is, an exercise not limited by the availability of muscle glycogen stores, given adequate diet.
The underlying mechanisms for the ergogenic effect of carbohydrates during this type of activity are not metabolic but may reside in the central nervous system: it seems that carbohydrates are detected in the oral cavity by unidentified receptors, promoting an enhanced sense of well-being and improving pacing.
These effects are independent of taste or sweet and non-sweet of carbohydrates but are specific to carbohydrates.

It should be noted that performance effects with drink ingestion are similar to the mouth rinse; therefore athletes, when they don’t complain of gastrointestinal distress when ingesting too much fluid, may have an advantage taking the drink (in endurance sports, dehydration and carbohydrate depletion are the most likely contributors to fatigue).

Conclusion

It seems that during exercise of relatively short duration (<1 h) and high intensity (>75% VO2max) it is not necessary to ingest large amounts of carbohydrates: a carbohydrate mouth rinsing or the intake of very small amounts of carbohydrates may be sufficient to obtain a performance benefit.

References

Hydration before endurance sports

Dehydration and endurance sports

Pre-hydration
Fig. 1 – Pre-hydration

In endurance sports, like Ironman, open water swimming, road cycling, marathon, or cross-country skiing, the most likely contributors to fatigue are dehydration and carbohydrate (especially liver and muscle glycogen) depletion.

Pre-hydration

Due to sweat loss needed to dissipate the heat generated during exercise, dehydration can compromise exercise performance.
It is important to start exercising in a euhydrated state, with normal plasma electrolyte levels, and attempt to maintain this state during any activity.
When an adequate amount of beverages with meals are consumed and a protracted recovery period (8-12 hours) has elapsed since the last exercise, the athlete should be euhydrated.
However, if s/he has not had adequate time or fluids/electrolytes volume to re-establish euhydration, a pre-hydration program may be useful to correct any previously incurred fluid-electrolyte deficit prior to initiating the next exercise.

Pre-hydration program

If during exercise the nutritional target is to reduce sweat loss to less than 2–3% of body weight, prior to exercise the athlete should drink beverages at least 4 hours before the start of the activity, for example, about 5-7 mL/kg body weight.
But if the urine is still dark (highly concentrated) and/or is minimal, s/he should slowly drink more beverages, for example, another 3-5 mL/kg body weight, about 2 hours before the start of activity so that urine output normalizes before starting the event.

It is advisable to consume small amounts of sodium-containing foods or salted snacks and/or beverages with sodium that help to stimulate thirst and retain the consumed fluids.
Moreover, palatability of the ingested beverages is important to promote fluid consumption before, during, and after exercise. Fluid palatability is influenced by several factors, such as:

  • temperature, often between 15 and 21 °C;
  • sodium content;
  • flavoring.

And hyper-hydration?

Hyper-hydration, especially in the heat, could improve thermoregulation and exercise performance, therefore, it might be useful for those who lose body water at high rates, as during exercise in hot conditions or who have difficulty drinking sufficient amounts of fluid during exercise.
However there are several risks:

  • fluids that expand the intra- and extra-cellular spaces (e.g. glycerol solutions plus water) greatly increase the risk of having to void during exercise;
  • hyper-hydration may dilute and lower plasma sodium which increases the risk of dilutional hyponatraemia, if during exercise, fluids are replaced aggressively.

Finally, it must be noted that plasma expanders or hyper-hydrating agents are banned by the World Anti-Doping Agency (WADA).

Conclusion

“Pre-hydrating with beverages, if needed, should be initiated at least several hours before the exercise task to enable fluid absorption and allow urine output to return toward normal levels. Consuming beverages with sodium and/or salted snacks or small meals with beverages can help stimulate thirst and retain needed fluids” (Sawka et al., 2007).

References

Ingestion of solid, liquid or gel carbohydrates 60 min before exercise

Liquid Carbohydrate Ingestion
Fig. 1 – Liquid Carbohydrate Ingestion

The form of carbohydrates ingested before exercise may have different effects on both metabolism and performance. Moreover, the ingestion of solid foods slows gastric empty, digestion and absorption rates compared with liquid foods and this has a different impact on glycemia.
For these reasons, several studies have investigated the effects of the form of carbohydrates on glycemic responses, oxidation rates and performance.

  • Studies comparing solid versus liquid carbohydrates and solid versus gel carbohydrates have found no difference in glycemic responses between groups.
  • Studies that have investigated difference in performance effects have found no differences.
  • Furthermore, no differences are found in carbohydrate oxidation rates between the carbohydrate ingestion in the three forms during exercise.

Therefore, it seems not to be the form of ingested carbohydrates that can enhance or reduce performance (in addition, even glycogen synthesis doesn’t vary; study conducted with liquid or solid carbohydrates).

Conclusion

It is advisable that athlete ingests whichever form of carbohydrates best suits, based on his experience and cost-effectiveness of the product.

References

Hypoglycemia and carbohydrate ingestion 60 min before exercise

Hypoglycemia: strategies to limit it in susceptible subjects

Hypoglycemia: Fatigue
Fig. 1 – Fatigue

From several studies it appears that the risk of developing hypoglycemia (blood glucose < 3.5 mmol /l or < 63 mg/l) is highly individual: some athletes are very prone to develop it and others are much more resistant.
A strategy to minimize glycemic and insulinemic responses during exercise is to delay carbohydrate ingestion just prior to exercise: in the last 5-15 min before exercise or during warm-up (even though followed by a short break).
Why?

  • Warm-up and then exercise increase catecholamine concentrations blunting insulin response.
  • Moreover, it has been shown that ingestion of carbohydrate-containing beverages during a warm-up (even if followed by a short break) does not lead to rebound hypoglycemia, independent of the amount of carbohydrates, but instead increases glycemia. When carbohydrates are ingested within 10 min before the onset of the exercise, exercise will start before the increase of insulin concentration.

Therefore, this timing strategy would provide carbohydrates minimizing the risk of a possible reactive hypoglycaemia.
In addition, it is possible to choose low glycemic index carbohydrates that lead to more stable glycemic and insulinemic responses during subsequent exercise.

Example: a 5-6% carbohydrate solution, often maltodextrin (i.e. 50-60 g maltodextrin in 1000 ml) or maltodextrin plus fructose (e.g. respectively 33 g plus 17 g in 1000 ml).

An intriguing observation is the lack of a clear relation between hypoglycaemia and its symptoms (likely related to a reduced delivery of glucose to the brain). In fact, symptoms are often reported in the absence of true hypoglycemia and hypoglycemia is not always associated with symptoms. Though the cause of the symptoms is still unknown, it is clearly not related to a glycemic threshold.

Conclusion

Some athletes develop symptoms similar to those of hypoglycemia, even though they aren’t always linked to actual low glycemia. To minimize these symptoms, for these subjects an individual approach is advisable. It may include:

  • carbohydrate ingestion just before the onset of exercise or during warm-up;
  • choose low-to-moderate GI carbohydrates that result in more stable glycemic and insulinemic responses;
  • or avoid carbohydrates 90 min before the onset of exercise.

References

Carbohydrate ingestion 60 min before exercise

Introductory statement

Carbohydrates
Fig. 1 – Carbohydrates

An high-carbohydrate diet in the days before exercise, as well as ingestion of meals high in carbohydrate 3-4 h before exercise, better if with low glycemic index, can have positive effects on athlete’s performance.

For many years it has been suggested that ingestion of carbohydrates 30-60 min before exercise may adversely affect performance because it could cause hypoglycemia (blood glucose < 3.5 mmol/l or < 63 mg/l), a major contributor to fatigue. In fact, a typical athlete’s mantra is: “Avoid carbohydrate in the hour before exercise”!
What is the reason of that?
Glucose ingestion may cause hyperglycaemia followed by hyperinsulinaemina that may result in:

  • a rapid decline in glycemia 15-30 minutes after the onset of exercise, called rebound or reactive hypoglycaemia, most likely the result of:

I. an increase in muscle glucose uptake (due to the mobilization of GLUT-4 transporters by the action of insulin but also from physical activity itself);
II. the reduction in liver glucose output;

  • in addition, higher availability of carbohydrates to the muscle stimulates glycolysis and this, in combination to insulin-induced inhibition of lipolysis in both adipose tissue and muscle, results in a reduction in fat oxidation (apparently long-chain fatty acids, not medium-chain fatty acids). This may lead to premature glycogen depletion and early onset of fatigue (glycogen would be almost the only available fuel for working muscle).
    This effect is temporary, approximately lasting only for the first 20 min of exercise so, it is likely that this little glycogen breakdown has no significant effect on exercise performance.

Therefore, at least in theory, carbohydrate ingestion 60 minutes before exercise could affect performance but only two studies (Foster et al. 1979, e Kovisto et al. 1981) have reported a reduced endurance capacity while the majority of studies have reported no change or an improvement in performance.
To clarify these results, a systematic series of studies was done in trained subjects. The conclusion of these studies was that:

  • There is no effect of pre-exercise carbohydrate feeding on performance, even though in some cases hypoglycaemia did develop”.
  • There was no relationship between low blood glucose concentrations and performance”. (Jeukendrup and Killer S.C. 2010)

Conclusion

Ingestion of meals rich in carbohydrates 3-4 h before exercise is important for the increase of liver and muscle glycogen stores, or for their resynthesis in previously depleted muscle and liver.
Carbohydrate ingestion 30-60 min before exercise may be important in topping-up liver glycogen stores which serve to maintain blood glucose concentrations during exercise.
Based on the currently available scientific evidences, there is no reason to avoid carbohydrates 60 min before the onset of exercise, because they don’t seem to have any detrimental effect on performance.

References