Glycosidic bonds

Connect a sugar molecule to something else

Covalent bonds between:

 The -OH group on the anomeric carbon (usually C1) of a sugar
 The -OH group of another compound (may be another sugar molecular or something
else)
 Bond formation results in loss of H2O
 Named based on which carbons were joined together and the anomerism of the anomeric
carbon. E.g., α-1,4-glycosidic bonds joins the C1 (anomeric) carbon of the first
saccharide (whose hydroxyl group was oriented in the α configuration) to the hydroxyl
group on the C4 carbon of the next saccharide.
Digestion of Carbohydrates
Carbohydrates are primarily digested by amylases and brush border enzymes. Carbohydrates
can only be absorbed as monosaccharides, so these enzymes break large starch molecules all the
way down into single monosaccharides.

Note: Many dietary carbohydrates are in the form of starch, which is a mixture of amylose and
amylopectin (both are made entirely of glucose molecules):

 Amylose is a straight chain of glucose molecules joined with α-1,4-glycosidic bonds.

 Amylopectin includes numerous branches formed by α-1,6-glycosidic bonds.

Amylases
 Cleave α-1,4 glycosidic bonds between sugar molecules
 Create smaller and smaller polysaccharide chains until most α-1,4 glycosidic bonds are
broken leaving:
1. Monosaccharides
2. Disaccharides
3. Oligosaccharides
4. Indigestible starches (sugars joined by other types of bonds)
Active at higher pH:
 Active in the mouth and small intestines
 Inactivated in the stomach
Types and location of amylase:
 Salivary amylase: secreted in the mouth by salivary glands
 Pancreatic amylase: secreted into the duodenum by the exocrine pancreas
Amylopectin is partially digested by amylase.
Amylopectin molecules are chains of glucose,
joined together by α-1,4-glycosidic bonds
(create a straight chain of glucose molecules)
and α-1,6-glycosidic bonds (create a branch off
the straight chain). Amylase breaks the α-1,4-
glycosidic bonds.
.
Brush border enzymes
Brush border

enzymes
are membrane-bound
proteins
on the luminal surface of enterocytes in the
small intestine
. There are 4 major brush-border
enzymes
involved in carbohydrate
digestion
.

 Isomaltase: cleaves α-1,6-glycosidic bonds

 Maltase: Splits maltose → glucose + glucose

Splits maltotriose → glucose + glucose + glucose

Lactase: splits lactose → glucose + galactose
Sucrase: Splits sucrose → glucose + fructose
Splits other small oligosaccharides

Absorption of Carbohydrates
After digestion, carbohydrates are absorbed and transported via the blood to the portal
circulation. Transport may be either an active, facilitated, or passive mechanism.
 Active transport involves the use of transporter enzymes, which uses energy to move
carbohydrates across the plasma membrane even against the concentration gradient.
 Facilitated diffusion occurs down concentration gradients with the additional aid of
transmembrane enzymes that do not require energy.
  Passive absorption moves sugars down concentration gradients without enzymatic
assistance or energy needed; it is the slowest mechanism.

Transporters have specific roles, and their functions may be active, facilitated, or passive.

Sodium–glucose-linked transporter 1 (SGLT1):

 Found in the luminal membrane of enterocytes in the small intestine
 Functions to transport glucose and galactose into the enterocytes
 Relies on an actively generated sodium gradient generated by a Na+/K+-ATPase
 Transports 2 sodiums, 1 glucose or galactose, and water
Glucose transporter 2 (GLUT2)
 Found in kidney, liver, and pancreas and on the basolateral membrane of enterocytes in
the small intestine
 Transports all 3 primary monosaccharides (glucose, galactose, and fructose) via
facilitated diffusion
 With regard to absorption: GLUT2 moves monosaccharides out of the enterocytes and
into the interstitial space.
 Bidirectionality allows for a change in function depending on cellular conditions.
GLUT5
 Transports fructose via facilitated diffusions

Passive glucose absorption represents a minority of absorptive capabilities. Most absorption

occurs in the 1st part of the small intestine (duodenum, jejunum).
Order of events in monosaccharide absorption:
1. Absorption into the enterocytes across the apical membrane:
 Glucose and galactose: via SGLT1
 Fructose: via GLUT5
2. Release into the interstitial space through GLUT2 on the basolateral membrane via
facilitated diffusion
3. Absorption into capillaries from the interstitial space
4. Capillaries drain into veins → portal vein → liver for metabolism
Absorption of monosaccharides across enterocytes
SGLT1: sodium–glucose-linked transporter
GLUT5: glucose transporter 5
GLUT2: glucose transporter 2
Monosaccharide Transport Within the Body
Once in the blood, monosaccharides are transported to cells throughout the body and absorbed
into peripheral cells by a number of different transporters. Several important glucose transporters
include:

GLUT4:
Most important glucose-uptake transporter
Expressed the most in skeletal muscle and adipose tissue
Stimulated by insulin to move circulating glucose into cells for use and/or storage
SGLT2:
Located in the proximal convoluted tubule (PCT) in the kidneys
Responsible for > 90% of filtered glucose reabsorption
Clinical Relevance
Lactose intolerance: malabsorptive GI disorder caused by a deficiency in lactase, a brush border
enzyme involved in the digestion and absorption of lactose. Lactose is a disaccharide composed
of glucose and galactose. Patients with lactose intolerance present with abdominal pain, diarrhea,
and flatulence after consuming lactose products. Treatment is dietary modification or lactase
supplementation in milder cases.
Galactosemia: autosomal recessive condition that prevents galactose processing due to a
deficiency in 1 of 3 key enzymes, the most common is galactose-1-phosphate uridylyltransferase.
Galactosemia is a serious condition that presents early in life in infants, who experience lethargy,
nausea, vomiting, diarrhea, and jaundice. Later manifestations can include neurodevelopmental
symptoms, cataracts, growth delay, and premature ovarian insufficiency. Treatment is dietary
modification.
Diabetes mellitus: metabolic condition caused by chronic hyperglycemia. Diabetes mellitus is
due to deficiency in or resistance to insulin. GLUT4 transporters are insulin-sensitive and help
promote the storage of glucose under certain conditions. Patients with type 2 diabetes mellitus
have a disruption in their response to insulin and thus glucose accumulates in the blood, causing
the chronic hyperglycemia. Symptoms include urinary frequency, increased thirst, and increased
appetite. Serious complications of diabetes mellitus include diabetic ketoacidosis, cardiovascular
disease, neuropathy, and kidney disease.