Carbohydrates
Overview
Definitions
- Carbohydrates: Compounds consisting of carbon, oxygen, and hydrogen that are classified as either simple (e.g., glucose, fructose, sucrose) or complex sugars (e.g., starch).
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Monosaccharide: a simple carbohydrate that cannot be further broken down by simple hydrolysis
- Examples: glucose, fructose, or galactose
- Disaccharide: formed by the union of two monosaccharides linked by a glycosidic bond
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Polysaccharide: formed by many monosaccharides bound by glycosidic bonds
- Examples: glycogen, cellulose, starch, peptidoglycans, glycosaminoglycans
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Glycosidic bond: linkage between a carbohydrate and another molecule (e.g., carbohydrate, alcohol)
- Two forms:
- 1,4 α-glycosidic bond (OH group below the plane of the ring)
- Example: maltose
- 1,4 β-glycosidic bonds (OH above the plane of the ring)
- Examples: lactose and cellulose
- 1,4 α-glycosidic bond (OH group below the plane of the ring)
- Two forms:
Lactase is the only enzyme in the human body that can cleave β-glucosidic bonds, but only those of the disaccharide lactose. There are no enzymes in the digestive tract that can cleave β-glycosidic bonds of polysaccharides. Cellulose therefore remains undigested in the intestine and is referred to as fiber!
Important disaccharides | |
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Name | Composed of |
Common table sugar |
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Maltose |
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Digestion and reabsorption
Carbohydrates in food
- Sources: table sugar, cereals, fruits, and vegetables
- About ⅔ in the form of starch (polysaccharide)
- About ⅓ in the form of disaccharides (e.g., lactose, sucrose)
Digestion
- Monosaccharides: absorbed directly by enterocytes
- Polysaccharides: broken down by enzymes into monosaccharides via hydrolytic cleavage of α-glycosidic bonds
Enzyme | Site | Chemical reaction |
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α-Amylase |
| Polysaccharides → maltose, isomaltose, maltotriose, other oligosaccharides |
Lactase |
| Lactose → galactose + glucose |
Sucrase-isomaltase | Maltose, isomaltose, maltotriose, saccharose → glucose + fructose | |
Maltase-glucoamylase | Polysaccharides, oligosaccharides, disaccharides → glucose |
- Lactase production decreases after breastfeeding, which leads to many individuals developing lactose intolerance.
Absorption
Glucose enters intestinal epithelial cells and proximal renal tubular cells via Na+-glucose-cotransporters (SGLT). In all other cells of the body, glucose uptake occurs through specific membranous glucose transporters (GLUT).
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Intestinal glucose absorption
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Sodium-dependent glucose cotransporter 1 (SGLT1)
- Specific transporter on the luminal side of mucosa cells, as well as the proximal straight tubule in the kidney
- The driving force is a sodium concentration gradient, which is maintained by basal Na+/K+ ATPase by transporting sodium out of the cell (secondary active transport).
- Sodium moves down its concentration gradient into the cell and takes a glucose molecule with it each time.
- Also absorbs galactose.
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Sodium-dependent glucose cotransporter 1 (SGLT1)
- Transport into blood: via GLUT2 and circulates unbound in blood
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Glucose uptake into cells
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Glucose transporter (GLUT)
- Group of specific glucose transporters that are present in the plasma membranes of almost all cells of the body.
- Passive transport via facilitated diffusion
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Glucose transporter (GLUT)
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Renal glucose reabsorption
- Free filtration of glucose by the kidneys
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Complete reabsorption in the proximal tubules via 2 types of SGLT → urine normally glucose free
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SGLT2: reabsorbs ∼ 98% of urinary glucose in the proximal convoluted tubule (PCT)
- One molecule of glucose is absorbed together with one molecule of sodium.
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SGLT1: reabsorbs the remaining glucose (∼ 2%) as well as galactose in the PST
- One molecule of glucose is absorbed together with two molecules of sodium.
- Fructose is absorbed via GLUT5 (glucose transporter).
- Reabsorption also relies on a sodium concentration gradient via Na+/K+ ATPase.
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SGLT2: reabsorbs ∼ 98% of urinary glucose in the proximal convoluted tubule (PCT)
Important glucose transporters
Name | Site | Special function | Insulin-dependent |
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GLUT1 |
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GLUT2 |
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GLUT3 |
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GLUT4 |
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GLUT5 |
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Only GLUT4 is insulin-dependent!
Maldigestion and malabsorption
- Lactose intolerance
- Fructose malabsorption
- Sucrose malabsorption (sucrase-isomaltase deficiency)
- Sorbitol malabsorption
Glucose metabolism
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See breakdown and synthesis of glucose for:
- Glucose degradation
- Glucose synthesis: gluconeogenesis
- See glycogen metabolism for glucose storage.
Galactose metabolism
Absorption of galactose
Galactose is part of lactose (found in milk products).
- Lactose is cleaved in the small intestine by the lactase.
- Freed galactose is absorbed by enterocytes via SGLT1.
- Transported into blood via GLUT2
- Circulates to the liver for further metabolism
Breakdown of galactose
Galactose metabolism converges with glucose metabolism after some intermediate steps: galactose → galactose-1-phosphate → UDP-galactose → UDP-glucose → glucose-1-phosphate (enters glycolysis).
- Galactokinase activates galactose: galactose + ATP → galactose-1-P + ADP
- Galactose-1-phosphate uridylyltransferase: galactose-1-P + UDP-glucose → UDP-galactose + glucose-1-P (can be fed into glycolysis)
- UDP-galactose 4-epimerase: UDP-galactose → UDP-glucose
If an individual is deficient of the enzyme galactose-1-phosphate UDT transferase (classical galactosemia), galactose and lactose (galactose + glucose) have to be removed from the diet!
High blood levels of galactose also result in conversion to the osmotically active galactitol via aldose reductase. In individuals with galactokinase deficiency, excess galactitol forms in the lens of the eye and leads to early-onset cataracts!
Galactose synthesis
- Metabolic site: lactating breast (lactose is the main sugar of breast milk)
- Reversal of all reactions
Disorders of galactose metabolism
Fructose metabolism
Absorption of fructose
Fructose is part of sucrose (a common table sugar).
- Sucrose is cleaved in the small intestine by sucrase-isomaltase.
- Freed fructose is absorbed into enterocytes via facilitated diffusion by GLUT5.
- Transported into blood via GLUT2
- Circulates to the liver for further metabolism
Breakdown of fructose (fructolysis)
Fructose metabolism converges with glucose metabolism after some intermediate steps: fructose + ATP → fructose-1-P → glyceraldehyde-3-P → glycolysis
- Fructokinase activates fructose: fructose + ATP → fructose-1-P + ADP
- Aldolase B splits hexose into two trioses: fructose-1-P → dihydroxyacetone-P + glyceraldehyde
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Conversion to glyceraldehyde-3-P:
- Triosephosphate isomerase: dihydroxyacetone-P (can directly enter glycolysis) → glyceraldehyde-3-P
- Triose kinase: glyceraldehyde + ATP → glyceraldehyde-3-P
- Glyceraldehyde-3-P is fed into glycolysis
If an individual is deficient in the enzyme aldolase B (hereditary fructose intolerance), both fructose and sucrose (glucose + fructose) have to be removed from the diet!
Fructose synthesis
Fructose can be produced from glucose via sorbitol (osmotically active sugar alcohol) without using ATP.
- Aldose reductase reduces glucose to sorbitol: glucose + NADPH → sorbitol
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Sorbitol dehydrogenase oxidates sorbitol to fructose: sorbitol + NAD+ → fructose
- In liver, ovaries, seminal vesicles
- In the body, fructose is the primary source of energy for spermatozoa.
Tissues that do not have sorbitol dehydrogenase activity (e.g., lens, retina, kidneys, Schwann cells) accumulate sorbitol. Excess sorbitol causes osmotic damage and explains changes seen in hyperglycemic diabetic patients such as diabetic cataracts, diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy.
Disorders of fructose metabolism
- Hereditary fructose intolerance (autosomal recessive defect of aldolase B)
- Essential fructosuria (autosomal recessive defect of fructokinase)