Lecture 13/14. Biochemistry 3521 - Fordham University - 1999

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Some of this material is taken and modified from:

Many Figures were kindly provided by R. Morse at Illinois State University

"Bichemistry" - Stryer (1995)

Biochemistry 3033 at Florida International University (kind permission of Dr. Kelsey Downum)

Biochemistry 242 at Illinois State University (kind permission of Dr. Reef Morse)

Biochemistry 460 at Arizona (Dr. Tischler)

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Version: 2/18/99

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TOPICS TO BE COVERED

A. Bioenergetics, High Energy Phosphates, and Energy Flux in Metabolism

B. Coenzymes

C. Carbohydrates

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Next Lecture

Glycolysis

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For a guide to study metabolism in this course see:

How to Study Metabolism

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A. Bioenergetics, High Energy Phosphates, Energy Flux, and Coenzymes in Metabolism

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Metabolism is the study of energy flow in a biological system.

1) How cells extract energy (ATP) and reducing power from the environment (we will cover in this course)

2) How cells synthesize the precursors of their macromolecular structures (amino acids, lipids, nucleic acids, carbohydrates)(biosynthesis of nucleic acids and proteins will be covered in this course)

Free energy indicates the portion of the total energy of a system that is available for useful work.

The change in free energy for an enzyme reaction in the cell is denoted as G.

delta G = GIBBS FREE ENERGY = delta H - T x delta S

delta H = energy change at constant pressure

delta S = entropy, a measure of the randomness of a system

T = absolute temperature

This term can be calculated (eqn 1) for an enzyme reaction in the cell by knowing the concentrations of the product(s) and reactant(s), and the standard free energy constant, G^o' (the prime indicates that pH = 7.0).

• When considering a metabolic pathway, the G term is the most important, since G^o' is simply a point of reference.
• It is noteworthy that a decrease in product concentration lowers G so that the reaction becomes more favorable (LeChatelier Principle, mass action effect).

When an enzyme reaction in the cell yields energy it is an exergonic reaction and the free energy is negative. Such a reaction proceeds spontaneously.

An enzyme reaction requiring energy input is an endergonic reaction. The free energy is positive and it cannot proceed spontaneously. However, it can be driven by coupling to an exergonic reaction.

There is no net flux (movement) in either direction. Therefore, the free energy (G) is zero and the standard free energy is directly proportional to the equilibrium constant (Keq) (eqn 2). The equilibrium constant is the ratio of product(s) to reactant(s) when the reaction is at equilibrium.

1) decrease in energy

2) increase in entropy

Every metabolic pathway must be a thermodynamically favored process. HOWEVER, many individual reactions are unfavorable.

Reactions are said to be coupled when a thermodynamically unfavorable reaction (the free energy value is positive) is driven by coupling the reaction to a thermodynamically favorable reaction (the free energy value is negative).G for a metabolic pathway is the sum of the G values for each individual enzyme reaction. For a pathway to proceed from beginning to end, the overall G must be negative.

How does this work?

We can calculate whether or not a reaction will procede from reactants to products by using the following equation:

delta G = delta G⁰' + RT log([products]/[reactants])

... math...

K'eq = 10^{-[delta G0'/1.36]}

where -delta G⁰' is in Kcal/mole or kjoul/mol

• What this means is that if the ratio of products to reactants changes by a factor of 10, the energy taken up or given off by that change is 1.36 Kcal.

• delta G is an indication of the spontaneity of a reaction (if delta G is negative, the reaction favors the products).
• delta G is also a function of the ratio of the products to reactants.
• This means that if the ratio of products to reactants is far away from equilibrium, the system has more energy. In a sense, delta G tells us how much the reaction "wants" to go toward equilibrium
• So, delta G depends on the nature of the reactants (delta G^0' )
• delta G depends on the concentration of the reactants (log[products]/[reactants]

HIGH ENERGY PHOSPHATE BONDS:

Energy rich phosphorylated compounds:

• ATP (static figure from Biochemistry Illustrated) is the most common carrier of free energy = intermediate high energy phosphate compound (see also ATP via Chime)
• Other ATP figures (2D and 3D)
• It may be used for motion, signal amplification, biosynthetic processes and active transport and in mammals is derived mostly from the oxidation of fuels such as glucose and fatty acids (Fig. 17-1).
• The energy of ATP is stored in its two phosphoanhydride bonds
• ADP has one high energy phosphate bond whereas AMP has none
• Hydrolysis of one phosphoanhydride bond yields 7.3 kcal/mol (the free energy of hydrolysis is -7.3 kcal/mol showing a spontaneous reaction).
• The energy released drives endergonic reactions (those requiring energy input) allowing various biological processes to occur.
• Release of the terminal phosphate from ATP and other high energy phosphate compounds constitutes the high phosphoryl group transfer potential.
• Other compounds do not release their terminal phosphate easily (e.g., AMP) and this constitutes a low-energy phosphate potential. Oxidation of fuels (for example, carbohydrate and fats) provides the energy for ADP phosphorylation to ATP

 

Amount of ATP in the cell is only enough for 1-2 minutes of cellular activity

Therefore, ATP must be continously formed and replenished

a) Substrate-level phosphorylation whereby phosphate is transferred during enzymatic reactions of metabolic pathways

Direct transfer of a phosphoryl group from a higher energy compound to ADP captures energy released from a reaction

 

b) Oxidative phosphorylation, which occurs when ATP is synthesized using the energy produced during the reduction of oxygen to water in mitochondria

Oxidative phosphorylation and photophosphorylation use the energy produced by generating a proton gradient across a biological membrane to form ATP

 

During ATP utilization, generally inorganic phosphate (Pi) (see phosphate) is removed to produce ADP. Addition of phosphate onto ADP with energy input replaces the ATP.

 

One exception is the adenylate kinase (myokinase) reaction 2 ADP <---> ATP + AMP which is important for producing AMP.

A good example for the role of this enzyme and AMP production is during muscle contraction. With exercise, large amounts of ATP are consumed producing ADP. Because the myokinase reaction operates near equilibrium, the increase in ADP and decrease in ATP pushes the reaction to the right (as drawn above). While this only replaces half of the ATP from which the ADP was produced, more importantly it dramatically increases the concentration of AMP which normally is extremely low (0.2% of ATP). AMP is an important activator of energy producing pathways (e.g., glycolysis). Thus AMP acts as a signal of low energy in the cell and promotes fuel oxidation to replenish ATP supplies. During rest as ATP is replaced the myokinase reaction above operates to the left and lowers AMP concentration to its normal low levels.

• Consumption is coupled to endergonic phosphorylation events which form low energy phosphorylated compounds
• Consumption is required for biosynthetic processes such as DNA , RNA, and protein synthesis
• NTPs for many processes are synthesized from ATP and NDPs
• Consumption of ATP energizes endergonic physiological processes such as muscle contraction, ion transport etc., via conformationsl chancels in proteins (hydrolysis of ATP drives the reaction by making it essentially irreversible)

Average person at rest consumes 3 mol ATP/h, during strenuous exercise 30 mol ATP/hour

Some other compounds have higher energy phosphate bonds and therefore also have a greater potential for transferring the phosphoryl group.

For instance: phosphocreatine + ADP ---> creatine + ATP is favored over the reverse direction because hydrolysis of creatine phosphate yields 10.3 kcal/mole.

 

The energy difference between ATP and creatine phosphate hydrolysis is -3 kcal/mol making the reaction exergonic (giving off energy).

When two or more reactions occur together, the overall free energy change for these reactions equals the sum of the free energy change for the individual steps.

For example:

 

Examples of favorable reactions: (highly energonic)

The first reaction is the more common hydrolysis

 

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See Phosphate for more information on the structure of phosphate esters,

phosphoanhydride, inorganic phosphate, etc 

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• Combination of electrostatic repulsion and resonance stabilization ----->coiled spring analogy
• Note that other phosphate molecules have even higher potential energy -- creatine phosphate, etc.

These large delta G really are due to special properties of reactants and products in the reactions.

for example: (see Stryer p. 446-448 for more detailed discussion)

A and B could be a change in protein conformation, reactants going to products, moving something from one side of a membrane to another (transport), etc.

• NOTE!! The coupling of ATP shifts the equilibrium toward the right by a factor of 10⁸!

1) delta G depends on temperature.

2) delta G^0' is defined at pH 7.0, pH varies.

delta G for hydrolysis of ATP to ADP is more negative in alkaline pH.

ADP-2 <=> ADP-3 + H

 

3) Mg2+, which interacts with the first and second phospate groups of ATP, varies in concentration depending on relative affinities of reactants and products for the ion.

 

4) Most importantly, ATP, ADP, and Pi concentrations vary from standard conditions (1 M).

Actual levels = 8, 1, 8 mM respectively.

Under actual conditions, delta G is actually closer to -12 Kcal/mole. (shifts equilibrium by 6.3 X 10⁸)

• couple exergonic reactions (nutrient oxidations) with endergonic reactions (maintain living state)
• phototrophs / autotrophs
• plants & bacteria use photosynthesis and capture light energy to convert carbon dioxide and water to carbohydrates, etc.
• oxidize organic compounds from outside sources to obtain energy

• anabolism - refers to synthetic processes (e.g. amino acid ---> protein)
• biosynthesis using common intermediates like pyruvate, acetyl CoA, etc. provide starting materials for the synthesis of most biomolecules
• catabolism- refers to degradative processes (e.g. glucose ---> CO₂)
• degradation to form energy (ATP, NADPH)
• large numbers of diverse substrates (carbohydrates, lipids, proteins) are degraded into common intermediates like acetyl CoA, which ends up in the citric acid cycle,
• then the electron transport system to undergo oxidative phosphorylation
• rate limiting step - the slowest reaction in a pathway and therefore determines the rate for the pathway

• reduced molecules --> oxidized molecules + energy
• net product is ATP (which is used to shift reaction equilibria)

See Overview of Intermediary Metabolism

1. Formation of smaller molecules (e.g. proteins to amino acids; fats to fatty acids).

• Fats, Polysaccharides, Proteins = Storage
• Breaking down polymers into individual units produces no useful energy in general
• Fatty acids, glucose, and amino acids

2. Formation of simple units; primarily acetyl CoA.
• Fatty acids, glucose, and amino acids: Break these down to common intermediate = acetyl CoA
• Ex. Glucose via glycolysis.
• This produces some ATP

3. Citric acid cycle (NADH production) and oxidative phosphorylation
• Further oxidation of acetyl-CoA combined with oxidative phosphorylation generates most ATP

General principle: synthesis DOES NOT EQUAL degradation -- these are carried out by different pathways.

• Irreversible - if two metabolites can be interconverted, the pathway from 1 to 2 must be different from 2 to 1; this allows for separate control of the two pathways
• Committed step - pathways operate near equilibrium, but there is usually an irreversible reaction which once is carried out commits the metabolized substrate to be through the pathway
• Regulation of the rate limiting step - control of the pathway usually occurs at the first committed step, which is usually also the rate limiting step
• Compartmentalization (eukaryotic cells) ---> Examples

ATP

mitochondria - ATP is generated

cytosol - ATP is utilized

 

Acetyl CoA

mitochondria - synthesized

cytosol - utilized

• Series of reactions and the energetics of the reactions (ex. leading from nutrients to products)
• Mechanism by which intermediates move on to successor molecules, requiring knowledge about the specific enzymes
• Control mechanisms which regulate the flow of metabolites or substrates through a pathway

 

Metabolism acts as an ATP buffer

That is, it keeps a certain ratio of ATP to its precursors ADP and AMP.

The cell reads this ratio to define its current metabolic state and adjusts the rate of degradative (energy generating) or biosyntheitic pathways (energy utilizing or storage of energy) accordingly.

Energy Charge = [ATP] + 1/2[ADP]/[ATP] + [ADP] + [AMP]

Enzyme kinetics is the simplest means the cell has to control the rate of an enzyme reaction.

For most enzymes, substrates are present near their Km value so that a small change in the concentration of the substrate can produce a significant increase or decrease in flux through that enzyme step. This also ensures uniform flux in a pathway where the product of the preceding enzyme is the substrate for the subsequent enzyme.

 

Allosterism occurs when an inhibitor or activator binds to a site on an enzyme molecule that is distinct from the active site. Binding can have a profound affect on the the rate of a substrate to product conversion that may greatly exceed typical changes in velocity due to alterations in substrate concentrations.

 

Feedback inhibition is negative modulation of enzyme activity by an end product or intermediate of a pathway acting at an earlier regulated step in that pathway (usually an irreversible reaction); sometimes reaction products may feedback to inhibit their own formation if theybecomes excessive.

 

Covalent modification occurs when some chemical group (usually phosphate derived from ATP) is covalently bonded to the enzyme to either increase or decrease the enzyme activity.

Such regulation is generally initiated in response to a hormone signal at the surface of the cell membrane. The interaction at the membrane via a receptor ultimately leads to phosphorylation of enzymes

 Regulatory proteins (e.g., calmodulin ) stimulate or inhibit enzymes by their direct interaction with the catalytic portion of an enzyme.

 

Proteolytic activation involves the removal of a portion of the polypeptide chain of the enzyme to convert it from an inactive to an active form.

Blood coagulation and digestive enzymes

 

Induction involves the biosynthesis of new enzyme molecules by initiating gene transcription

• Induction is generally in response to specific hormonal signals in the nucleus.
• Repression is opposite to this process; that is inhibition of enzyme synthesis.
• The amount of enzyme can be controlled by degradation of enzyme molecules.
• The overall balance of formation and degradation of any protein represents its turnover rate.

 

Compartmentation: Sites of Biochemical Pathways in the Cell

• Glycolysis and fatty acid synthesis occur in the cytosol since they produce some products which may be exported from the tissue.
• Note that certain pathways commence in the mitochondrial matrix and finish in the cytosol.
• This occurs because the starting reactants are found in the mitochondria and the products of these pathways (i.e., glucose, from gluconeogenesis, and urea, from the urea cycle) must be excreted from the organ (liver or kidney).
• The major oxidative processes (citric acid cycle, ß-oxidation of fatty acids) occur in close conjunction with oxidative phosphorylation.

Coenzymes are molecules that cooperate in the catalytic action of an enzyme.

Coenzyme may be tightly bound to the protein = prosthetic group

Ex. = Heme in hemoglobin

 

Or it may be free to diffuse away from the enzyme, acting as an additional substrate = cofactor

Ex. = FAD and NAD (ATP) (Static Images)

see also stick model of NAD

see also ATP using Chime

This could also include cations required for many reactions

Ex. = Mg or Zn

They are moderately reduced compounds (some oxygen associated with them) which can be converted into energy (ATP) quickly

1) Energy storage, fuel, intermediates of metabolism

2) Structural - DNA and RNA, cell walls in plants (cellulose), arthropods skeleton (chitin)

3) Recognition - attached to lipids and proteins (blood types on red blood cells = antigens)

• Building blocks --> polysaccharides (macromolecules)
• D-Configuration is the most common in sugars synthesized by living organisms
• D assignment is based on the configuration of the chiral carbon furthest from the "anomeric" carbon
• C-1 in aldoses & C-2 in ketoses
• Two major monosaccharide classes (see Tutorial at Iowa State for Fisher structures or Stryer Figs. 18-3 and 18-4)

• Aldoses
• Ketoses

• Aldoses
• Structures based on D-glyceraldehyde which is the simplest aldose (3C)(asymmetric carbon)
• D is determined by the asymmetric carbon FURTHEST AWAY from the aldehyde and is drawn to the RIGHT!
• Aldoses contain an aldehyde group
• Have 1-4 chiral centers per molecule
• Be familiar with both open chain & ring forms
• Know structures of glucose



D-glyceraldehyde                               L-glyceraldehyde

• Ketoses
• Structures based on dihydroxyacetone (simplest ketose)
• D is determined by the asymmetric carbon FURTHEST AWAY from the ketone and is drawn to the RIGHT!
• Contain a carbonyl group
• Have 1,2 or 3 chiral carbons per molecule
• Know the structures of ribulose & fructose



dihydroxyacetone

• Nomenclature
• The number of carbons are indicated by the prefix for the sugar such that hexoses (e.g., glucose and fructose) contain 6 carbons and pentoses contain 5 carbons. (see Tutorial at Iowa State for Fisher structures)
• triose 3
• tetrose 4
• pentose 5
• hexose 6
• heptose 7

• Carbohydrates are rich in stereoisomerism
• Enantiomers = isomers that are perfect mirror images (i.e., D- and L- glyceraldehyde)
• Diastereoisomers = not mirror images (i.e., D-erythrose and D-threose)
• Epimers = isomers that differ at a single asymmetric carbon --- Hexose examples
• Glucose vs mannose at carbon 2
• Gucose vs galactose at carbon 4
• see Tutorial at Iowa State for Fisher structures or Stryer Figs. 18-3 and 18-4

• CONFIGURATIONS OF CARBOHYDRATES:
• Asymmetric carbons are those which have four different chemical groups attached.
• Glucose has four different asymmetric carbons (#2,3,4,5).
• Look at epimers of glucose
• Allose, altrose, and mannose
• Carbons in sugars are numbered beginning at the end nearest the aldehyde or ketone group.
• The "D" or "L" designation for a sugar designates the arrangement of the atoms around the asymmetric carbon farthest from the aldehyde or ketone.
• Most sugars in humans are D-sugars.

Glucose = C₆H₁₂O₆

• Anomeric carbon is the new asymmetric carbon formed when an alcohol (COH) group in a monosaccharide reacts with the aldehyde or ketone to form a cyclic compound.
• The anomeric carbon can either be alpha or beta, depending on the orientation of the alcohol group on the anomeric carbon relative to the CH₂OH group.
• Glucose forms a 6-membered pyranose ring consisting of 5 carbons and 1 oxygen. (see below)
• Fructose forms a 5-membered furanose ring containing one less carbon. (see below)
• Found in fruits

• In solution, monosaccharides (aldoses & ketoses) with 5 or more carbons are most stable in their "ring" form
• In the ring form, the carbonyl carbon becomes covalently bound to another OH-group within the chain.
• Carbonyl carbon becomes the "anomeric" carbon after cyclization
• Most common ring structures
• pyranose ring - 6-membered ring (5- or 6-carbon monosaccharides)(see figure with glucose ring formation below)
• Glucose = six-carbon aldose
• C-1 reacts with C-5 OH to form pyranose ring
• Conformation of hydroxyl on carbon 1
• alpha (below plane of ring)
• beta (above plane of ring)
• See Figure Illustrating Aldose Conversion into Pyranose ring for Glucose
• furanose ring - 5-membered ring (most 5-carbon monosaccharides) (see figure with fructose ring formation below)
• Fructose = six-carbon ketose
• C-2 reacts with C-5 OH to form furanose ring
• C-1 reacts with C-5 OH to form pyranose ring
• Conformations (see below)
• See Figure Illustrating Ketose Conversion into Pyranose or Furanose ring for Fructose
• Anomers or Anomeric Carbon = After cyclization, the anomeric OH-group can be above, or below, the plane of the ring
• alpha-D sugars have the OH-group on the anomeric carbon below the plane of the ring
• beta-D sugars have the OH-group on the anomeric carbon above the plane of the ring in glucopyranose
• The beta form (beta-D glucopyranose) is the preferred form (62%), with alpha-D-glucopyranose accounting for the remaining 38%.
• a and b forms interconvert in water through straight-chain forms(mutarotation)
• D-glucose in solution is 1/3 a and 2/3 b (1% open chain) - these are anomers
• Chair vs boat form of pyranose ring

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• After entering a cell, sugars are immediately phosphorylated by addition of phosphate usually derived from ATP.
• Such phosphorylated sugars are key intermediates in metabolic pathways and can interact in electrostatic interactions
• One important reason for phosphorylating sugars is to prevent them from leaving the cell. Phosphate groups accomplish this because they have a high negative charge associated with them readily cross cell membranes. Some phosphorylated sugars are highly reactive and can transfer phosphate to ADP to form ATP.

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• How are the monomers linked together?
• Use the chemistry of hydroxyl and carbonyl groups
• -O- Glycosidic bonds (oxygen) analog of the peptide bond = removal of water
• no mutarotation since opening and re-closing of the ring form no longer possible
• broken down by glycosidases via addition of water

 

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Disaccharides

• Two monosaccharides joined by a O-glycosidic bond (see Stryer Fig. 18-10)
• Glycosidic bond - catalyzed by hydrolase (dehydration reaction) to form R-O-R linkage
• Glycosidic bonds hold together the monosaccharides in a polysaccharide. The bond is formed when the anomeric hydroxyl group condenses with an alcohol group on a second monosaccharide.
• Anomeric OH-group from one sugar reacts with an OH-group on another sugar
• Reaction generally leaves one "anomeric" carbon
• Disaccharides common in nature (see Figures of sucrose, lactose, and maltose)
• sucrose - disaccharide containing fructose + glucose linked via an alpha (1->2) linkage (no free anomeric carbon) glucose alpha(1->2)-beta-fructose
• alpha-D-glucopyranosyl - (1-->2) - beta-D-fructofuranoside
• lactose (milk sugar) - a disaccharide consisting of galactose + glucose linked by a beta (1->4) linkage (free anomeric carbon) - galactose beta (1->4)glucose
• Beta-D-galactopyranosyl - (1-->4) - alpha-D-glucopyranose
• Lactose intolerance
• In the intestine lactase hydrolyzes lactose, a disaccharide, to galactose and glucose by cleaving a ß1,4-galactosidic bond.
• Approximately one in 4 adults is deficient in this enzyme leading to lactose intolerance.
• Up to 90% of Asians and Africans may be lactase-deficient as adults. Lactose accumulates in the intestine due to poor absorption. Bacteria produce metabolites of lactose leading to fluid influx into the intestine. Clinical symptoms include distension, nausea, cramping, watery diarrhea. Lactose must be removed from the diet.
• maltose - 2 glucopyranose units joined by an alpha (1->4) linkage (free anomeric carbon)
• alpha form - glucose alpha (1->4)-alpha-glucose
• beta form - glucose alpha (1->4)-beta-glucose
• Alpha-D-glucopyranosyl - (1-->4) - alpha-D-glucopyranose

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Oligosaccharides - 2-8 monosaccharides linked by glycosidic bonds

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Polysaccharides (glycans) - polymers of monosaccharides (8 or more) linked by glycosidic bonds. In contrast to the other biomolecules, sugars can form branched as well as linear polymers.

Sugar polymers of high molecular weight (can be over 10⁶ residues)(dextrans are alpha 1,6 bonds)

 

Storage (energy) Homopolysaccharides - polysaccharides composed of only one type of sugar involved

• Starch (plants) - consists of two types of glucose homopolysaccharides (storage form of glucose)
• Structural forms
• Alpha-amylose - alpha(1->4) linked glucopyranose polymer
• Unbranched, irregular helical coiled conformation
• Amylopectin - alpha(1->4) glucopyranose polymer with alpha(1->6) branch points
• Branches ~ every 30th bond
• Up to 10⁶ residues
• Starch is plant primary food reserve and is deposited in insoluble granules
• Breakdown of dietary starch in mammals
• enzyme a-amylase (in saliva and pancreas) breaks internal alpha-1,4 linkages to give maltose, maltotriose, and alpha-dextrin (a 1,6's and a 1,4's)
• chain length reduced from 1000s to 8 glucose residues
• we cannot cleave alpha(1->6)

• Glycogen (animals) - storage form of glucose in cytoplasm of most cells, but particularly high in liver & skeletal muscles of animals (stored as granules)
• Glycogen is similar to amylopectin, but more highly branched
• alpha(1->4) linked glucopyranose polymer with alpha(1->6) branch points ~ every 10th bond
• (see Stryer Fig 18-13, p. 473)
• Glycogen requires two enzymes for degradation
• One to hydrolyze alpha(1->4 linkages (alpha-amylase in digestive system or glycogen phosphorylases in cells)
• One to hydrolyze alpha(1->6) linkages (debranching enzyme in cells)
• Glycogenolysis in liver and release of free glucose into blood stream when blood glucose drops
• Glycogenesis in liver when blood glucose is high by transport of glucose into liver and synthesis of glycogen

Structural homopolysaccharides

• Cellulose (plants) - beta(1->4) linked glucopyranose polymer - one of the most resistant natural polymers made (see Stryer Fig. 18-14)
• plant cell walls
• maintains shape
• withstands osmotic pressure changes
• as many as 15,000 D-glucose residues linked by beta-1,4 linkages (we can't digest this linkage)
• ruminants have protozoa and bacteria that contain cellulase (mutualistic symbiosis)
• unbranched - gives straight chain
• stabilized by hydrogen bonds
• makes long fibrils with high tensile strength
• Chitin (invertebrate exoskeleton) - beta(1->4) linked N-acetylglucosamine polymer
• Therefore, like cellulose except N-acetyl group at C-2 in residues

• Cell walls of fungi & algae are also a polymer of N-acetylglucosamine with b 1,4 unbranched linkages  - is very strong

 

Heteropolysaccharides

• Polysaccharides composed of two or more types of monosaccharide units
• Gycosaminoglycans consist of repeating disaccharide units with negatively charged groups
• Many are linked to proteins and are known as proteoglycans
• Important in connective tissue (see Stryer Fig. 18-15), basement membrane, synovial fluid of joints, and in the extracellular matrix between cells -- Examples
• Hyaluronic acid or hyaluronate
• beta(1->3) linked glucuronic (COOH in 6 positions) and N-acetyl-D-glucosamine polymer
• Chondroitin 6-sulfate
• Heparin (anticoagulant)
• Keratin sulfate

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OTHER COMPLEX CARBOHYDRATES

• Glycoproteins ---> CHO residues on Proteins = Involved in Cell Recognition/Cell Adhesion
• Modified monosaccharides (fucose and sialic acid) are often attached at b bends or beta-turns
• O-glycosylation = Polysaccharides are attached to serine or theronine OH forming -O-glycosidic bonds
• Disaccharide core of galactose b 1,3 N-acetylgalactosamine
• Can be branched CHO from this basal unit
• N-glycosylation = Polysaccharides are attached to asparagine R-group amine forming -N-glycosidic bonds
• N-acetylglucoseamine is the first sugar in the unit with branched CHO attached
• N-linked carbohydrates have a common core:




• Another carbohydrate found on proteins is sialic acid

• Common linkage is -gal-sia by an alpha- 2,3 linkage
• Possible role of sialic acid: protein recycling
• New proteins in blood for example, immunoglobins and some hormones, are synthesized with sialic acids present.
• With time, sialic acids are removed (sialidase).
• Enzyme recognized asialoglycoprotein, binds it, and takes it up into liver cells where it is digested.
• Other roles include:
• cell binding
• cell-cell recognition

• UDP-glucose

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Course Study Aid:

How to Study Metabolism 

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Other Internet Sites with Similar or Supporting Material

Carbohydrate Structure Tutorial at Iowa State

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 Lecture 14 - 3521 

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