7.1 Monosaccharides and Disaccharides

Monosaccharides are aldoses or ketoses

Carbohydrates are aldehydes or ketones bearing several hydroxyl groups, together with their derivatives
A monosaccharide cannot be hydrolysed to a smaller sugar unit, while a disaccharide is two monosaccharides joined by a glycosidic bond
Carbon number gives trioses, pentoses and hexoses, and the carbonyl type gives aldoses and ketoses
Glucose is an aldohexose with an aldehyde at C1 and fructose a ketohexose with a ketone at C2
The formula of an unsubstituted monosaccharide is CnH2nOn, yet cells contain many derivatives
Phosphorylation, oxidation and amination change function greatly, so the formula alone does not fix a role

표 7.1-1Aldoses and ketoses compared

Figure 7-1Relation between mono-, di- and polysaccharides and their main functions

Figure 7-2Fischer projections of open-chain D-glucose (an aldose) and D-fructose (a ketose)

Monosaccharides contain chiral centres

A chiral carbon bears four different atoms or groups, and dihydroxyacetone is the exception with none
In a Fischer projection horizontal bonds come toward the viewer and vertical bonds go behind the page
D/L is relative configuration, R/S is CIP absolute configuration and (+)/(-) is measured rotation, and none can be substituted for another
D sugars predominate in biology, though not every biological sugar is D
An epimer differs at exactly one of several chiral centres, so D-mannose is the C2 epimer and D-galactose the C4 epimer of D-glucose
Glucose and fructose differ in carbonyl position and connectivity and are therefore not epimers
With n independent chiral centres there are at most 2 to the n stereoisomers, giving 16 for an aldohexose and 8 for a ketohexose

Figure 7-3Mirror-image relation of D-glucose and L-glucose in open-chain Fischer projections

Figure 7-4Carbon-by-carbon OH arrangement in D-glucose, D-mannose and D-galactose

Figure 7-5Number of possible isomers against the count of chiral centres in open-chain monosaccharides

Common monosaccharides are cyclic

The C5 hydroxyl oxygen of glucose attacks the C1 aldehyde carbon to give an intramolecular hemiacetal and a six-membered pyranose ring
This is an intramolecular nucleophilic addition, not a dehydration condensation, and ketoses form a hemiketal instead
The former carbonyl carbon becomes the anomeric carbon, usually C1 in an aldose and C2 in fructose
In the Haworth projection with C5-CH2OH up, an OH below C1 means alpha and above means beta
The alpha and beta definition rests on the relative arrangement of the anomeric substituent and a reference carbon, so it also applies to L sugars
Mutarotation is the change in observed rotation as ring opening and closing equilibrate the alpha and beta forms
Reported values near 20 degrees Celsius are about +112 degrees for alpha, +19 for beta and +52.7 for the equilibrium mixture
Fructose forms fructofuranose when C5-OH adds and fructopyranose when C6-OH adds, and sucrose contains the furanose form

Figure 7-6Open-chain D-glucose and formation of the intramolecular hemiacetal

Figure 7-7Anomeric substituent orientation in alpha- and beta-D-glucopyranose

Figure 7-8D/L, alpha/beta and optical rotation signs are three separate notation systems

Figure 7-9Mutarotation of alpha- and beta-D-glucose; the time course is a teaching exponential model, not measured data

Figure 7-10Conceptual skeleton of the fructose ring-closure path, omitting per-atom substituent geometry

Cells contain many hexose derivatives

Sugars serve not only as fuel but as surface recognition signals, extracellular matrix components and building blocks of glycans
Glucosamine carries an amino group in place of the C2 hydroxyl, and N-acetylation gives N-acetylglucosamine
Glucuronic acid has an oxidised carboxyl at C6 and exists as glucuronate at physiological pH
Fucose is a 6-deoxy sugar found in glycoproteins and recognition glycans
These modifications change solubility, charge and recognition and thereby determine function

표 7.1-2Representative hexose derivatives

Figure 7-11Representative hexose derivatives and the positions at which they are modified

[Separate note 7-1] Measuring blood glucose in diagnosis

The hexokinase method phosphorylates glucose with ATP and couples glucose 6-phosphate oxidation to reduction of NADP+ to NADPH
The rise in absorbance at 340 nm is proportional to glucose under suitable conditions
Glucose oxidase methods measure oxygen consumption and the resulting hydrogen peroxide or electron-transfer signal
Example: with epsilon 6.22 L per mmol per cm and A340 0.311 the cuvette holds 0.0500 mmol/L, so a 100-fold dilution is 5.00 mmol/L, about 90.1 mg/dL
ADA 2026 criteria for non-pregnant adults: HbA1c at least 6.5 percent, fasting plasma glucose at least 126 mg/dL and a 2-hour value of at least 200 mg/dL after 75 g
With typical hyperglycaemic symptoms a random plasma glucose of at least 200 mg/dL is diagnostic
Without a crisis a confirmatory test is usual, and home meters or continuous monitors must not be the sole basis for a decision

표 7.1-3Prediabetes and diagnostic thresholds in non-pregnant adults

Figure 7-12Main reactions and detection signals of the glucose oxidase and hexokinase methods

Figure 7-13Absorbance against NADPH concentration in the hexokinase method (theoretical calibration line)

Figure 7-14Main glycaemic thresholds for non-pregnant adults; the diagnostic tests differ

Monosaccharides can act as reducing agents

A reducing sugar can be oxidised under suitable conditions and reduce another substance
A free hemiacetal or hemiketal anomeric centre allows the ring to open to the reactive chain form
Glucose, maltose and lactose are reducing, and fructose, though a ketose, rearranges through an enediol to an aldose form in alkali
Cu2+ in Benedict reagent is reduced to Cu+ in hot alkali and gives a brick-red Cu2O precipitate
Colour intensity cannot establish the identity or exact concentration of a particular sugar
Sucrose is not reducing before hydrolysis

Figure 7-15Presence of a free anomeric carbon and its relation to reducing power

Figure 7-16Reduction of Cu(II) by a reducing sugar and formation of Cu2O precipitate

Figure 7-17Expected Benedict results for glucose, fructose, maltose, lactose and sucrose (simulated)

Monosaccharides form disaccharides through glycosidic bonds

A disaccharide is an O-glycosidic structure formed when the hydroxyl of one anomeric centre reacts with a hydroxyl of another sugar
Alpha or beta states the configuration of the participating anomeric centre and (1-4) or (1-2) gives the linked carbons
Cellular synthesis uses activated sugar nucleotides rather than simple condensation of neutral sugars
Maltose with alpha(1-4) and lactose with beta(1-4) retain a free anomeric carbon and are reducing
Sucrose with alpha(1-2)beta and trehalose with alpha(1-1)alpha have both anomeric carbons fixed and are non-reducing
Hydrolysis consumes one water and the enzymes involved are selective for bond configuration and sugar type
Example: 34.23 g of sucrose, 0.1000 mol, gives 0.1000 mol each of glucose and fructose, 18.02 g of each

표 7.1-4Composition and reducing behaviour of the main disaccharides

Figure 7-18Model of O-glycosidic bond formation between two monosaccharides

Figure 7-19Sugar composition and linkage positions of maltose, lactose, sucrose and trehalose

Figure 7-20Substrate selectivity and products of maltase, lactase and sucrase

[Separate note 7-2] Sweetness and what else follows

Sweetness does not correspond directly to whether a sugar is reducing
Sweet-tasting molecules act through T1R2 and T1R3 taste receptors
Glucose, fructose, sucrose and lactose differ in structure, and perceived sweetness changes with concentration, temperature and mixture
The claim that equal sugar mass means equal sweetness and equal blood glucose response does not hold
WHO treats added sugars and the free sugars of honey, syrups and juice as a separate category
Molecular chemistry, food labelling and glucose control are different levels and must be interpreted separately

Figure 7-21Reducing power, sweetness and glycaemic response are independent properties

Figure 7-22Flow of ideas in 7.1, from stereochemistry to biological assay

References

**표 7.1-1**Aldoses and ketoses compared
Feature	Aldose	Ketose
Carbonyl group	Terminal -CHO	Internal >C=O
Examples	Glucose, galactose, ribose	Fructose, dihydroxyacetone
Reactive carbon	Aldehyde carbon (C1 of glucose)	Ketone carbon (C2 of fructose)

**표 7.1-2**Representative hexose derivatives
Derivative	Key structural change	Biological meaning
Glucosamine	C2-OH replaced by -NH2	Building block of amino sugars and glycans
N-Acetylglucosamine	Acetylated amino group at C2	Component of chitin and glycoproteins
Glucuronic acid	C6 primary alcohol oxidised to carboxyl	Conjugation reactions and glycosaminoglycans
Fucose	6-Deoxy form	Glycoprotein and cell-recognition glycans

**표 7.1-3**Prediabetes and diagnostic thresholds in non-pregnant adults
Test	Prediabetes range	Diabetes threshold
Fasting plasma glucose	100-125 mg/dL	at least 126 mg/dL
2-hour oral glucose tolerance	140-199 mg/dL	at least 200 mg/dL
HbA1c	5.7-6.4 percent	at least 6.5 percent
Random plasma glucose	Not used for prediabetes	Typical symptoms or crisis plus at least 200 mg/dL

**표 7.1-4**Composition and reducing behaviour of the main disaccharides
Disaccharide	Monosaccharides	Glycosidic bond	Reducing
Maltose	Glc + Glc	alpha(1-4)	Yes
Lactose	Gal + Glc	beta(1-4)	Yes
Sucrose	Glc + Fru	alpha(1-2)beta, both anomeric carbons	No
Trehalose	Glc + Glc	alpha(1-1)alpha	No

**Figure 7-1**Relation between mono-, di- and polysaccharides and their main functions

**Figure 7-2**Fischer projections of open-chain D-glucose (an aldose) and D-fructose (a ketose)

**Figure 7-3**Mirror-image relation of D-glucose and L-glucose in open-chain Fischer projections

**Figure 7-4**Carbon-by-carbon OH arrangement in D-glucose, D-mannose and D-galactose

**Figure 7-5**Number of possible isomers against the count of chiral centres in open-chain monosaccharides

**Figure 7-6**Open-chain D-glucose and formation of the intramolecular hemiacetal

**Figure 7-7**Anomeric substituent orientation in alpha- and beta-D-glucopyranose

**Figure 7-8**D/L, alpha/beta and optical rotation signs are three separate notation systems

**Figure 7-9**Mutarotation of alpha- and beta-D-glucose; the time course is a teaching exponential model, not measured data

**Figure 7-10**Conceptual skeleton of the fructose ring-closure path, omitting per-atom substituent geometry

**Figure 7-11**Representative hexose derivatives and the positions at which they are modified

**Figure 7-12**Main reactions and detection signals of the glucose oxidase and hexokinase methods

**Figure 7-13**Absorbance against NADPH concentration in the hexokinase method (theoretical calibration line)

**Figure 7-14**Main glycaemic thresholds for non-pregnant adults; the diagnostic tests differ

**Figure 7-15**Presence of a free anomeric carbon and its relation to reducing power

**Figure 7-16**Reduction of Cu(II) by a reducing sugar and formation of Cu2O precipitate

**Figure 7-17**Expected Benedict results for glucose, fructose, maltose, lactose and sucrose (simulated)

**Figure 7-18**Model of O-glycosidic bond formation between two monosaccharides

**Figure 7-19**Sugar composition and linkage positions of maltose, lactose, sucrose and trehalose

**Figure 7-20**Substrate selectivity and products of maltase, lactase and sucrase

**Figure 7-21**Reducing power, sweetness and glycaemic response are independent properties

**Figure 7-22**Flow of ideas in 7.1, from stereochemistry to biological assay