Metabolism of Monosaccharides and Disaccharides - PowerPoint PPT Presentation

About This Presentation
Title:

Metabolism of Monosaccharides and Disaccharides

Description:

Title: PowerPoint Presentation Last modified by: Administrator Created Date: 1/1/1601 12:00:00 AM Document presentation format: On-screen Show (4:3) – PowerPoint PPT presentation

Number of Views:1080
Avg rating:3.0/5.0
Slides: 21
Provided by: lectureug9
Category:

less

Transcript and Presenter's Notes

Title: Metabolism of Monosaccharides and Disaccharides


1
Metabolism of Monosaccharides and Disaccharides
  • ASAB
  • Tahir A. Baig

2
OVERVIEW
  • Glucose is the most common monosaccharide
    consumed by humans, and its metabolism has been
    discussed extensively.
  • However, two other monosaccharidesfructose and
    galactoseoccur in significant amounts in the
    diet, and make important contributions to energy
    metabolism.
  • In addition, galactose is an important component
    of cell structural carbohydrates.
  • Figure shows the metabolism of fructose and
    galactose as part of the essential pathways of
    energy metabolism in the body.

3
(No Transcript)
4
FRUCTOSE METABOLISM
  • About 10 of the calories contained in the
    Western diet are supplied by fructose
    (approximately 50 g/day).
  • The major source of fructose is the disaccharide
    sucrose, which, when cleaved in the intestine,
    releases equimolar amounts of fructose and
    glucose.
  • Fructose is also found as a free monosaccharide
    in many fruits, in honey, and in high-fructose
    corn syrup (55 fructose/45 glucose), which is
    used to sweeten soft drinks and many foods.
  • Entry of fructose into cells is not
    insulin-dependent and in contrast to glucose,
    fructose does not promote the secretion of
    insulin.

5
A. Phosphorylation of fructose
  • For fructose to enter the pathways of
    intermediary metabolism, it must first be
    phosphorylated (Figure 12.2).
  • This can be accomplished by either hexokinase or
    fructokinase (also called ketohexo-kinase).
  • Hexokinase phosphorylates glucose in all cells of
    the body, and several additional hexoses can
    serve as substrates for this enzyme. However, it
    has a low affinity for fructose.
  • Therefore, unless the intracellular concentration
    of fructose becomes unusually high, the normal
    presence of saturating concentrations of glucose
    means that little fructose is converted to
    fructose 6-phosphate by hexokinase.
  • Fructokinase provides the primary mechanism for
    fructose phosphorylation (Figure 12.2).
  • It is found in the liver (which processes most of
    the dietary fructose), kidney, and the small
    intestinal mucosa, and converts fructose to
    fructose 1-phosphate, using ATP as the phosphate
    donor.
  • Note These three tissues also contain aldolase
    B, discussed below.

6
B. Cleavage of fructose 1-phosphate
  • Fructose 1 -phosphate is not phosphorylated to
    fructose 1,6-bisphos-phate as is fructose
    6-phosphate, but is cleaved by aldolase B (also
    called fructose 1-phosphate aldolase) to
    dihydroxy-acetone phosphate (DHAP) and
    glyceraldehyde.
  • Note Both aldolase A (found in all tissues) and
    aldolase B cleave fructose 1,6-bisphosphate
    produced during glycolysis to DHAP and
    glyceraldehyde 3-phosphate, but only aldolase B
    cleaves fructose 1-phosphate R DHAP can directly
    enter glycolysis or gluconeogene-sis, whereas
    glyceraldehyde can be metabolized by a number of
    pathways, as illustrated in Figure 12.3.
  • C. Kinetics of fructose metabolism
  • The rate of fructose metabolism is more rapid
    than that of glucose because the trioses formed
    from fructose 1 -phosphate by pass
    phos-phofructokinasethe major rate-limiting step
    in glycolysis.

7
D. Disorders of fructose metabolism
  • A deficiency of one of the key enzymes required
    for the entry of fructose into intermediary
    metabolic pathways can result in either a benign
    condition (fructokinase deficiency), or a severe
    disturbance of liver and kidney metabolism as a
    result of aldolase B deficiency (hereditary
    fructose intolerance, HFI), which is estimated to
    occur in 120,000 live births (Figure 12.3).
  • The first symptoms of HFI appear when a baby is
    weaned and begins to be fed food containing
    sucrose or fructose. Fructose 1-phosphate
    accumulates, resulting in a drop in the level of
    inorganic phosphate (Pi) and, therefore, of ATP
    As ATP falls, AMP rises. In the absence of Pj,
    AMP is degraded, causing hyperuricemia.
  • The decreased availability of hepatic ATP affects
    gluconeogenesis (causing hypoglycemia with
    vomiting), and protein synthesis (causing a
    decrease in blood clotting factors and other
    essential proteins).
  • Diagnosis of HFI can be made on the basis of
    fructose in the urine, or by a restriction
    fragment length polymorphism test (RFLP).
  • In HFI, sucrose as well as fructose, must be
    removed from the diet to prevent liver failure
    and possible death.

8
E. Conversion of mannose to fructose 6-phosphate
  • Mannose, the C-2 epimer of glucose, is an
    important component of glycoproteins.
  • Hexokinase phosphorylates mannose, producing
    mannose 6-phosphate, which, in turn, is
    (reversibly) isomerized to fructose 6-phosphate
    by phospho-mannose isomerase.
  • Note There is little mannose in dietary
    carbohydrates. Most intracellular mannose is
    synthesized from fructose, or is preexisting
    mannose produced by the degradation of structural
    carbohydrates and salvaged by hexokinase.

9
(No Transcript)
10
F. Conversion of glucose to fructose via sorbitol
  • Most sugars are rapidly phosphorylated following
    their entry into cells.
  • They are thereby trapped within the cells,
    because organic phosphates cannot freely cross
    membranes without specific transporters.
  • An alternate mechanism for metabolizing a
    monosaccharide is to convert it to a polyol by
    the reduction of an aldehyde group, thereby
    producing an additional hydroxyl group.
  • Synthesis of sorbitol
  • Aldose reductase reduces glucose, producing
    sorbitol (glucitol, Figure 12.4).
  • This enzyme is found in many tissues, including
    the lens, retina, Schwann cells of peripheral
    nerves, liver, kidney, placenta, red blood cells,
    and in cells of the ovaries and seminal vesicles.
  • In cells of the liver, ovaries, sperm, and
    seminal vesicles, there is a second enzyme,
    sorbitol dehydrogenase, that can oxidize the
    sorbitol to produce fructose (Figure 12.4).
  • The two-reaction pathway from glucose to fructose
    in the seminal vesicles is for the benefit of
    sperm cells, which use fructose as a major
    carbohydrate energy source.
  • The pathway from sorbitol to fructose in the
    liver provides a mechanism by which any available
    sorbitol is converted into a substrate that can
    enter glycolysis or gluconeogenesis.

11
(No Transcript)
12
2. The effect of hyperglycemia on sorbitol
metabolism
  • Because insulin is not required for the entry of
    glucose into the cells listed in the previous
    paragraph, large amounts of glucose may enter
    these cells during times of hyperglycemia, for
    example, in uncontroller diabetes.
  • Elevated intracellular glucose concentrations and
    a adequate supply of NADPH cause aldose reductase
    to produce a significant increase in the amount
    of sorbitol, which cannot pass efficiently
    through cell membranes and, therefore, remains
    trapped inside the cell (Figure 12.4).
  • This is exacerbated when sorbitol dehydrogenase
    is low or absent, for example, in retina, lens,
    kidney, and nerve cells.
  • As a result, sorbitol accumulates in these cells,
    causing strong osmotic effects and, therefore,
    cell swellin as a result of water retention.
  • Some of the pathologic alterations associated
    with diabetes can be attributed, in part, to this
    phenomenon, including cataract formation,
    peripheral neuropathy, and vascular problems
    leading to nephropathy and retinopathy.

13
(No Transcript)
14
III. GALACTOSE METABOLISM_
  • The major dietary source of galactose is lactose
    galactosyl ß-1,4-glucose) obtained from milk and
    milk products.
  • Some galactose can also be obtained by lysosomal
    degradation of complex carbohydrates, such as
    glycoprotein and glycolipids, which are important
    membrane components.
  • Like fructose, the entry of galactose into cells
    is not insulin-dependent.

A. Phosphorylation of galactose Like fructose,
galactose must be phosphorylated before it can be
further metabolized. Most tissues have a specific
enzyme for this purpose, galactokinase, which
produces galactose 1-phosphate (Figure 12.5). As
with other kinases, ATP is the phosphate
donor. B. Formation of UDP- galactose Galactose
1-phosphate cannot enter the glycolytic pathway
unless it is first converted to UDP-galactose
(Figure 12.5). This occurs in an exchange
reaction, in which UDP-glucose reacts with
galactose 1-phosphate, producing UDP-galactose
and glucose 1-phosphate (Figure 12.6). The enzyme
that catalyzes this reaction is galactose
1-phosphate uridyltransferase.
15
(No Transcript)
16
  • C. Use of UDP- galactose as a carbon source for
    glycolysis or gluconeogenesis
  • For UDP- galactose to enter the mainstream of
    glucose metabolism, it must first be converted to
    its C-4 epimer, UDP-glucose, by UDP-hexose
    4-epimerase.
  • This "new" UDP-glucose (produced from the
    original UDP-galactose) can then participate in
    many biosynthetic reactions, as well as being
    used in the Uridyltransferase reaction described
    above, converting another galactose 1 -phosphate
    into UDP-galactose, and releasing glucose 1
    -phosphate, whose carbons are those of the
    original galactose. (Figure 12.5).
  • D. Role of UDP-galactose in biosynthetic
    reactions
  • UDP-galactose can serve as the donor of galactose
    units in a number of synthetic pathways,
    including synthesis of lactose (see below),
    glycoproteins, glycolipids, and
    gly-cosaminoglycans.
  • Note If galactose is not provided by the diet
    (for example, when it cannot be released from
    lactose as a result of a lack of p-galactosidase
    in people who are lactose- intolerant), all
    tissue requirements for UDP-galactose can be met
    by the action of UDP-hexose 4-epimerase on
    UDP-glucose, which is efficiently produced from
    glucose 1 -phosphate (Figure 12.5).

17
(No Transcript)
18
  • E. Disorders of galactose metabolism
  • Gatactose 1 -phosphate Uridyltransferase is
    missing in individuals with classic galactosemia
    (Figure 12.5).
  • In this disorder, galactose 1 -phosphate and,
    therefore, galactose accumulate in cells.
  • Physiologic consequences are similar to those
    found in essential fructose intolerance, but a
    broader spectrum of tissues is affected.
  • The accumulated galactose is shunted into side
    pathways such as that of galactitol production.
    This reaction is catalyzed by aldose reductase,
    the same enzyme that converts glucose to
    sor-bitol (39). Note A more benign form of
    galactosemia is caused by a deficiency of
    galactokinase (see Figure 12.5).

19
IV. LACTOSE SYNTHESIS__
  • Lactose is a disaccharide that consists of a
    molecule of ß -galactose attached by a ß(1-4)
    linkage to glucose.
  • Therefore, lactose is galactosyl
    ß(1-4)-glucose. Lactose, known as the "milk
    sugar," is produced by the mammary glands of most
    mammals. Therefore, milk and other dairy products
    are the dietary sources of lactose.
  • Lactose is synthesized in the Golgi by lactose
    synthase (UDP-galactoseglucose
    galactosyltransferase), which transfers galactose
    from UDP-galactose to glucose, releasing UDP
    (Figure 12.7).
  • This enzyme is composed of two proteins, A and B.
    Protein A is a ß-D-gatactosyltransferase, and is
    found in a number of body tissues. In tissues
    other than the lactating mammary gland, this
    enzyme transfers galactose from UDP-galactose to
    N-acetyl-o glucosamine, forming the same ß(1 -gt4)
    linkage found in lactose, and producing
    N-acetyllactosaminea component of the
    structurally important N-linked-glycoproteins.
  • In contrast, protein B is found only in lactating
    mammary glands. It is a-lactalbumin, and its
    synthesis is stimulated by the peptide hormone,
    prolactin.
  • Protein B forms a complex with the enzyme,
    protein A, changing the specificity of that
    transferase so that lactose, rather than
    N-acetyllactosamine, is produced (Figure 12.7).

20
(No Transcript)
Write a Comment
User Comments (0)
About PowerShow.com