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What is the definition of a carbohydrate?

Polyhydroxy aldehydes or ketones, or molecules that yield them on hydrolysis; empirical formula (CH2O)n, though amino and deoxy sugars do not fit exactly.

How are carbohydrates classified by carbonyl group?

Aldose: carbonyl at C-1 (aldehyde). Ketose: carbonyl at C-2 (ketone).

How are carbohydrates classified by carbon number?

Triose (3C), tetrose (4C), pentose (5C), hexose (6C).

How are carbohydrates classified by size?

Monosaccharide (1 unit), disaccharide (2 units), oligosaccharide (3-10 units), polysaccharide (many units).

What is the D/L rule for sugars?

Find the highest-numbered chiral carbon (farthest from carbonyl). -OH on the right = D; -OH on the left = L.

Why are human sugars D?

Human enzymes and transporters are stereospecific for D-sugars; D-glucose is the biological form, not L-glucose.

How many stereoisomers exist for a molecule with n chiral centers?

2^n. An aldohexose has 4 chiral centers → 16 isomers (8 D, 8 L).

What are constitutional isomers?

Same molecular formula but different connectivity (e.g., glucose vs fructose: aldose vs ketose).

What are enantiomers?

Non-superimposable mirror images; differ at every chiral center (e.g., D-glucose vs L-glucose).

What are diastereomers?

Stereoisomers that are NOT mirror images; differ at some but not all chiral centers.

What are epimers?

Diastereomers that differ at exactly one chiral center.

What are glucose's two important epimers?

Galactose (C-4 epimer) and mannose (C-2 epimer).

What is the relationship between galactose and mannose?

They differ at two carbons (C-2 and C-4), so they are diastereomers but NOT epimers.

What are anomers?

Epimers that differ only at the anomeric carbon, formed on ring closure (e.g., α-D-glucose vs β-D-glucose).

What happens when a sugar cyclizes in water?

An -OH on the same chain attacks the carbonyl: aldehyde + alcohol → hemiacetal; ketone + alcohol → hemiketal.

What is the anomeric carbon?

The former carbonyl carbon, which becomes a new chiral center on ring closure (C-1 in glucose, C-2 in fructose).

What is the difference between pyranose and furanose?

Pyranose = six-membered ring (e.g., glucose). Furanose = five-membered ring (e.g., fructose).

In a Haworth projection, what does α vs β mean?

α: anomeric -OH down (trans to CH2OH). β: anomeric -OH up (cis to CH2OH).

What is mutarotation?

α and β anomers interconvert through the open chain until equilibrium (~63% β, ~36% α, <1% open chain).

What is a reducing sugar?

A sugar with a free anomeric carbon that can open to an aldehyde and reduce Cu2+ (Benedict's test: blue → brick-red Cu2O).

Are all monosaccharides reducing?

Yes, including fructose, because it can isomerize to an aldose under alkaline test conditions.

What is sucrose's reducing status and why?

Sucrose is NON-reducing because both anomeric carbons (glucose C-1 and fructose C-2) are locked in the glycosidic bond.

What is the difference between O-glycosidic and N-glycosidic bonds?

O-glycosidic: sugar-sugar or sugar-Ser/Thr. N-glycosidic: sugar-base in nucleotides or sugar-Asn in N-linked glycoproteins.

What is the notation for a glycosidic bond?

e.g., Glc-α(1→4)-Glc: anomer, first carbon number, arrow, second carbon number.

What is a sugar alcohol?

A sugar whose carbonyl is reduced to -OH (e.g., sorbitol, xylitol, mannitol). No carbonyl → no ring, no anomeric carbon, not reducing.

Why is xylitol used in sugar-free gum?

Sugar alcohols are poorly fermented by oral streptococci, so little acid is produced and enamel demineralization is reduced.

What are amino sugars?

Sugars with -OH replaced by -NH2, often N-acetylated (e.g., glucosamine, GlcNAc, GalNAc). Found in GAGs, mucins, bacterial cell walls.

What are sugar acids?

Sugars with carbon oxidized to -COOH (e.g., glucuronic acid in GAGs; sialic acid capping glycoproteins).

What are deoxy sugars?

Sugars with an -OH replaced by -H (e.g., 2-deoxyribose in DNA; fucose in blood-group antigens).

What are the monosaccharides and linkage of maltose?

Glucose + glucose; Glc-α(1→4)-Glc; reducing; digested by maltase.

What are the monosaccharides and linkage of lactose?

Galactose + glucose; Gal-β(1→4)-Glc; reducing; digested by lactase (a β-galactosidase).

What are the monosaccharides and linkage of sucrose?

Glucose + fructose; Glc-α(1↔2)β-Fru; NON-reducing; digested by sucrase.

Which disaccharide is non-reducing and why?

Sucrose, because both anomeric carbons are involved in the glycosidic bond, so no free aldehyde can form.

Why is sucrose especially cariogenic?

S. mutans glucosyltransferases split sucrose and use its bond energy to build sticky, insoluble glucans that form the plaque matrix; released sugars are fermented to lactic acid.

What is the Stephan curve?

A graph of plaque pH after sugar exposure: pH falls below the critical ~5.5 within minutes, then recovers over 30-60 minutes as saliva buffers.

Why does frequency of sugar exposure matter more than amount?

Each exposure restarts the pH drop, keeping plaque pH below the critical threshold for longer, increasing demineralization.

What is the critical pH for enamel demineralization?

~5.5; below this, hydroxyapatite begins to dissolve.

What is amylose?

Linear α(1→4)-linked glucose polymer from plant starch; coils into a helix.

What is amylopectin?

Plant starch with α(1→4) backbone and α(1→6) branches every ~24-30 residues.

What is glycogen?

Animal storage polysaccharide with α(1→4) backbone and α(1→6) branches every ~8-12 residues; more branched than amylopectin.

Why is glycogen more branched than amylopectin?

More branches = more non-reducing ends = faster glucose release when needed.

What is cellulose?

β(1→4)-linked glucose polymer; humans lack enzymes to cleave β(1→4) bonds, so it is indigestible fiber.

Why can humans digest starch but not cellulose?

Starch is α-linked; human amylase and α-glucosidases cleave α bonds. Cellulose is β(1→4)-linked; no human enzyme cleaves that bond.

What are N-linked glycoproteins?

Glycans attached to asparagine (Asn) residues; added in ER/Golgi.

What are O-linked glycoproteins?

Glycans attached to serine/threonine (Ser/Thr) residues; often start with GalNAc.

What are salivary mucins?

MUC5B and MUC7; heavily O-glycosylated proteins that lubricate oral tissues, form acquired pellicle, and aggregate bacteria.

What are glycosaminoglycans (GAGs)?

Long unbranched repeats of amino sugar + uronic acid, often sulfated and strongly negative; hold water. Examples: hyaluronan, chondroitin sulfate, heparan sulfate.

What is the ABO antigen core?

A shared H antigen core (...Gal + Fuc). Type A adds GalNAc; Type B adds Gal; Type O adds nothing.

What does lysozyme do?

Hydrolyzes the β(1→4) bond between NAM and NAG in bacterial peptidoglycan, lysing bacteria (especially Gram-positive).

Where is salivary α-amylase active and what does it do?

In the mouth; cleaves internal α(1→4) bonds of starch → maltose, maltotriose, α-limit dextrins. It cannot cut α(1→6).

What happens to salivary amylase in the stomach?

Gastric acid (pH 1.5-3.5) denatures it, so little carbohydrate digestion occurs there.

Where does starch digestion resume?

In the small-intestinal lumen, by pancreatic α-amylase after bicarbonate neutralizes chyme.

What brush-border enzymes finish carbohydrate digestion?

Maltase (maltose → glucose), sucrase (sucrose → glucose + fructose), isomaltase (α(1→6) bonds → glucose), lactase (lactose → glucose + galactose).

What form of carbohydrate is absorbed?

Only monosaccharides are absorbed; all di- and oligosaccharides must be hydrolyzed first.

How is glucose absorbed at the apical membrane?

SGLT1: Na+-coupled secondary active transport (glucose or galactose with 2 Na+).

How is fructose absorbed at the apical membrane?

GLUT5: facilitated diffusion.

How do monosaccharides exit the enterocyte?

GLUT2 at the basolateral membrane: facilitated diffusion of glucose, galactose, and fructose into the blood.

Where do absorbed monosaccharides go first?

Hepatic portal vein → liver.

What is the basis of oral rehydration therapy (ORT)?

SGLT1 co-transports glucose and Na+; water follows osmotically, making ORT more effective than water alone.

Which glucose transporter is insulin-responsive?

GLUT4, in skeletal muscle and adipose tissue; insulin moves it to the membrane.

Which glucose transporter is the β-cell glucose sensor?

GLUT2, in liver and pancreatic β-cells; low affinity, high capacity.

Which glucose transporter supplies the brain?

GLUT1, in brain and red blood cells; high affinity, always active.

Which glucose transporter is fructose-specific?

GLUT5, in the intestine (apical).

What is lactose intolerance?

Lactase deficiency → lactose reaches the colon undigested → osmotic diarrhea and bacterial fermentation (gas, organic acids).

What are the types of lactose intolerance?

Primary (age-related decline after weaning; most common), secondary (after gut injury), congenital (rare, from birth).

A patient develops bloating and diarrhea after milk. What enzyme is deficient and what bond is not hydrolyzed?

Lactase (β-galactosidase); the Gal-β(1→4)-Glc bond of lactose is not hydrolyzed.

Why does uncontrolled diabetes increase caries risk?

High blood glucose spills into saliva and gingival fluid, and reduced salivary flow decreases buffering, leading to more acid attacks on enamel.

Why does uncontrolled diabetes cause fruity breath?

Without effective insulin, cells cannot use glucose (GLUT4), so the body burns fat and makes ketone bodies; acetone gives the fruity odor.

Why defer elective invasive dental treatment in a patient with glucose 520 mg/dL and ketonuria?

Uncontrolled diabetes with possible ketoacidosis: impaired healing and high infection risk; refer to physician first.

A patient sips a sweetened drink slowly over two hours. Explain caries risk using the Stephan curve.

Each sip restarts the pH drop, so plaque pH stays below ~5.5 for most of the two hours instead of recovering; frequency drives demineralization.

Starch and cellulose are both glucose polymers. Why can we digest only one?

Starch is α-linked and human amylase/α-glucosidases cleave α bonds. Cellulose is β(1→4)-linked and no human enzyme cleaves that bond.

A freshly dissolved sample of pure α-D-glucose slowly changes optical rotation. Why?

Mutarotation: the ring opens and recloses through the open chain until α and β reach equilibrium (~36% α, ~63% β).

Why can sorbitol not form a glycosidic bond as the anomeric partner?

It is a sugar alcohol: its carbonyl has been reduced, so it cannot cyclize and has no anomeric carbon.

What is the net yield of glycolysis per glucose?

2 ATP, 2 NADH, and 2 pyruvate.

Where does glycolysis occur?

In the cytosol; no oxygen is required.

What are the three stages of glycolysis?

Stage 1 (steps 1-3): trap and prime, 2 ATP spent. Stage 2 (steps 4-5): cleave to two trioses. Stage 3 (steps 6-10, x2): payoff, 4 ATP and 2 NADH made.

Which enzyme catalyzes the committed, rate-limiting step of glycolysis?

Phosphofructokinase-1 (PFK-1).

What are the three irreversible steps of glycolysis and their enzymes?

1. Glucose → glucose-6-P (hexokinase/glucokinase). 2. Fructose-6-P → fructose-1,6-bisP (PFK-1). 3. PEP → pyruvate (pyruvate kinase).

What is the most potent activator of PFK-1?

Fructose-2,6-bisphosphate.

What inhibits PFK-1?

ATP, citrate, and H+ (low pH).

What activates PFK-1?

AMP and fructose-2,6-bisphosphate.

How does glucagon affect PFK-1 in the liver?

Glucagon → PKA phosphorylates PFK-2/FBPase-2 → fructose-2,6-bisP falls → PFK-1 off.

How does insulin affect PFK-1 in the liver?

Insulin → PFK-2 active → fructose-2,6-bisP rises → PFK-1 on.

Why does glucokinase, not hexokinase, work as the liver's glucose sensor?

Glucokinase has a high Km (~10 mM), so its rate rises and falls with blood glucose; hexokinase (low Km, ~0.1 mM) is already saturated at normal glucose levels.

What is the difference between hexokinase and glucokinase?

Hexokinase: low Km, found in most tissues, inhibited by glucose-6-P. Glucokinase: high Km, liver and pancreatic β-cells, not inhibited by glucose-6-P, induced by insulin.

Which transporter partners with glucokinase in liver and β-cells?

GLUT2 (high Km), allowing glucose uptake to track blood glucose.

Why must pyruvate be converted to lactate when oxygen is short?

Lactate dehydrogenase regenerates NAD+; without NAD+, glyceraldehyde-3-P dehydrogenase (step 6) stops and glycolysis halts.

What enzyme converts pyruvate to lactate?

Lactate dehydrogenase (LDH).

What is the Pasteur effect?

In the presence of oxygen, glycolysis slows because aerobic metabolism produces more ATP, inhibiting PFK-1.

How does fluoride reduce acid production by plaque bacteria?

It enters bacteria as HF, releases F- inside, and inhibits enolase (step 9), reducing PEP, pyruvate, and lactate production.

What is the main anticaries effect of fluoride?

Promoting enamel fluorapatite formation and remineralization; enolase inhibition is an added benefit.

Why is xylitol toxic to plaque bacteria?

It is taken up and phosphorylated by the PEP-driven sugar transport system, but xylitol-5-phosphate cannot enter glycolysis; it is dephosphorylated and expelled, creating a futile cycle that wastes bacterial energy.

Why do red blood cells depend on glycolysis?

They have no mitochondria, so glycolysis to lactate is their only ATP source.

What is the 2,3-BPG shunt and what does it do?

1,3-BPG → 2,3-BPG (costs one ATP; step 7 is skipped). 2,3-BPG binds deoxyhemoglobin and stabilizes it, shifting the O2 curve right and releasing more O2 to tissues.

What happens in pyruvate kinase deficiency?

Red cells cannot make enough ATP; cells stiffen and are removed by the spleen, causing hemolytic anemia.

How does fructose enter glycolysis?

Fructokinase → fructose-1-P → aldolase B → DHAP + glyceraldehyde → G3P. It enters below PFK-1, skipping the main control point.

How does galactose enter glycolysis?

Galactokinase → galactose-1-P → UDP-galactose → epimerase (C-4 inversion) → UDP-glucose → glucose-6-P.

Why is fructose metabolized faster than glucose in the liver?

It enters glycolysis below PFK-1, bypassing the main rate-limiting control step.

What are the four fates of glucose-6-phosphate?

1. Glycolysis. 2. Glycogen synthesis. 3. Pentose phosphate pathway. 4. Free glucose (liver and kidney only, via glucose-6-phosphatase).

A patient with type 1 diabetes took insulin but skipped breakfast and presents confused and sweaty with glucose 45 mg/dL. Why is the brain vulnerable?

The brain runs almost entirely on glucose (~120 g/day), stores little glycogen, and cannot use fatty acids. When blood glucose falls, neurons lose ATP within minutes.