BI3.1-6 | Chemistry and Metabolism of Carbohydrates — Glossary

This is glycolysis — arguably the oldest metabolic pathway on Earth.

In the diabetic clinic, you'll interpret HbA1c and fasting glucose to manage diabetes — India has over 100 million diabetics, more than any country on Earth.

In the emergency department, you'll treat diabetic ketoacidosis and hypoglycaemia — both can kill within hours.

In paediatrics, you'll encounter galactosaemia and glycogen storage diseases.

In surgery, you'll manage the metabolic stress response where cortisol drives gluconeogenesis.

And in the ICU, you'll balance insulin drips and glucose infusions while monitoring lactate — a direct product of anaerobic glycolysis.

Carbohydrates are polyhydroxy aldehydes or ketones, or compounds that yield them on hydrolysis.

1. Monosaccharides (single sugar units — cannot be hydrolysed further) Classified by: • Number of carbons: triose (3C, e.g., glyceraldehyde), pentose (5C, e.g., ribose), hexose (6C, e.g., glucose) • Functional group: aldose (aldehyde group, e.g.

• Number of carbons: triose (3C, e.g., glyceraldehyde), pentose (5C, e.g., ribose), hexose (6C, e.g., glucose) • Functional group: aldose (aldehyde group, e.g., glucose) or ketose (ketone group, e.g.

• Number of carbons: triose (3C, e.g., glyceraldehyde), pentose (5C, e.g., ribose), hexose (6C, e.g., glucose) • Functional group: aldose (aldehyde group, e.g., glucose) or ketose (ketone group, e.g.

• Number of carbons: triose (3C, e.g., glyceraldehyde), pentose (5C, e.g., ribose), hexose (6C, e.g., glucose) • Functional group: aldose (aldehyde group, e.g., glucose) or ketose (ketone group, e.g.

• Functional group: aldose (aldehyde group, e.g., glucose) or ketose (ketone group, e.g., fructose) The clinically important monosaccharides: • Glucose (aldohexose) — the universal fuel.

• Functional group: aldose (aldehyde group, e.g., glucose) or ketose (ketone group, e.g., fructose) The clinically important monosaccharides: • Glucose (aldohexose) — the universal fuel.

• Glucose (aldohexose) — the universal fuel.

• Fructose (ketohexose) — the sweetest natural sugar, found in fruits and honey.

• Galactose (aldohexose) — derived from lactose (milk sugar).

Must be converted to glucose in the liver; failure causes galactosaemia • Ribose (aldopentose) — the sugar backbone of RNA.

• Ribose (aldopentose) — the sugar backbone of RNA.

Deoxyribose is in DNA *Isomer alert:* Glucose, fructose, and galactose all have the formula C₆H₁₂O₆ — they're isomers.

*Isomer alert:* Glucose, fructose, and galactose all have the formula C₆H₁₂O₆ — they're isomers.

2. Disaccharides (two monosaccharides linked by a glycosidic bond) • Sucrose = glucose + fructose (table sugar, from sugarcane) — α-1,2 bond • Lactose = galactose + glucose (milk sugar) — β-1,4 bond.

• Sucrose = glucose + fructose (table sugar, from sugarcane) — α-1,2 bond • Lactose = galactose + glucose (milk sugar) — β-1,4 bond.

• Lactose = galactose + glucose (milk sugar) — β-1,4 bond.

• Maltose = glucose + glucose (from starch digestion) — α-1,4 bond 3.

3. Polysaccharides (long chains of monosaccharides) Homopolysaccharides (one type of sugar repeated): • Starch — the plant storage form of glucose.

Homopolysaccharides (one type of sugar repeated): • Starch — the plant storage form of glucose.

• Starch — the plant storage form of glucose.

• Glycogen — the animal storage form of glucose.

Metabolised mainly in the liver • Galactose (aldohexose) — derived from lactose (milk sugar).

Stored in liver (maintains blood glucose) and skeletal muscle (fuel for contraction).

• Cellulose — structural polysaccharide of plants.

Heteropolysaccharides (different sugars): • Glycosaminoglycans (GAGs) — hyaluronic acid, chondroitin sulphate, heparin.

• Glycosaminoglycans (GAGs) — hyaluronic acid, chondroitin sulphate, heparin.

Energy fuel — glucose → glycolysis → TCA → 30-32 ATP per molecule 2.

Storage — glycogen in liver and muscle (short-term energy reserve) 3.

Structural — ribose in nucleic acids, GAGs in connective tissue, glycoproteins on cell surfaces

Your body can only absorb monosaccharides — all dietary starch, sucrose, and lactose must be broken down first.

Step 1: Digestion (lumen of the GI tract) *Mouth:* Salivary α-amylase (ptyalin) begins starch digestion, cleaving α-1,4 bonds.

*Mouth:* Salivary α-amylase (ptyalin) begins starch digestion, cleaving α-1,4 bonds.

*Duodenum:* Pancreatic α-amylase takes over — the major enzyme for starch digestion.

It breaks starch into maltose, maltotriose, and α-limit dextrins (branched fragments with α-1,6 bonds that amylase can't cleave).

It breaks starch into maltose, maltotriose, and α-limit dextrins (branched fragments with α-1,6 bonds that amylase can't cleave).

• Maltase → cleaves maltose → 2 glucose • Sucrase → cleaves sucrose → glucose + fructose • Lactase → cleaves lactose → glucose + galactose • Isomaltase (α-dextrinase) → cleaves α-1,6 bonds in limit dextrins Step 2: Absorption (intestinal epithelium → blood) • Glucose and.

• Sucrase → cleaves sucrose → glucose + fructose • Lactase → cleaves lactose → glucose + galactose • Isomaltase (α-dextrinase) → cleaves α-1,6 bonds in limit dextrins Step 2: Absorption (intestinal epithelium → blood) • Glucose and galactose — absorbed by SGLT-1.

• Lactase → cleaves lactose → glucose + galactose • Isomaltase (α-dextrinase) → cleaves α-1,6 bonds in limit dextrins Step 2: Absorption (intestinal epithelium → blood) • Glucose and galactose — absorbed by SGLT-1 (sodium-dependent glucose transporter) on the luminal side.

• Isomaltase (α-dextrinase) → cleaves α-1,6 bonds in limit dextrins Step 2: Absorption (intestinal epithelium → blood) • Glucose and galactose — absorbed by SGLT-1 (sodium-dependent glucose transporter) on the luminal side.

Step 2: Absorption (intestinal epithelium → blood) • Glucose and galactose — absorbed by SGLT-1 (sodium-dependent glucose transporter) on the luminal side.

• Glucose and galactose — absorbed by SGLT-1 (sodium-dependent glucose transporter) on the luminal side.

• Glucose and galactose — absorbed by SGLT-1 (sodium-dependent glucose transporter) on the luminal side.

This is secondary active transport — glucose rides the Na⁺ gradient created by the Na⁺/K⁺ ATPase.

Then exits via GLUT-2 on the basolateral side into blood.

• Fructose — absorbed by GLUT-5 (facilitated diffusion, no energy required).

Step 3: Transport (blood → tissues) Glucose enters cells via GLUT transporters (a family of facilitated diffusion channels): • GLUT-1 — brain, RBCs (always on — glucose entry is constitutive, not insulin-dependent) • GLUT-2 — liver, pancreatic β-cells, intestine (low-affinity,.

Glucose enters cells via GLUT transporters (a family of facilitated diffusion channels): • GLUT-1 — brain, RBCs (always on — glucose entry is constitutive, not insulin-dependent) • GLUT-2 — liver, pancreatic β-cells, intestine (low-affinity, high-capacity — acts as a glucose.

• GLUT-1 — brain, RBCs (always on — glucose entry is constitutive, not insulin-dependent) • GLUT-2 — liver, pancreatic β-cells, intestine (low-affinity, high-capacity — acts as a glucose sensor) • GLUT-3 — neurons (high affinity — ensures brain always gets glucose) • GLUT-4 —.

• GLUT-3 — neurons (high affinity — ensures brain always gets glucose) • GLUT-4 — skeletal muscle, adipose tissue (insulin-dependent — in the absence of insulin, GLUT-4 stays hidden in vesicles inside the cell.

• GLUT-4 — skeletal muscle, adipose tissue (insulin-dependent — in the absence of insulin, GLUT-4 stays hidden in vesicles inside the cell.

• GLUT-1 — brain, RBCs (always on — glucose entry is constitutive, not insulin-dependent) • GLUT-2 — liver, pancreatic β-cells, intestine (low-affinity, high-capacity — acts as a glucose sensor) • GLUT-3 — neurons (high affinity — ensures brain always gets glucose) • GLUT-4 —.

Disorders: • Lactose intolerance — lactase deficiency (very common in Indian adults).

• Lactose intolerance — lactase deficiency (very common in Indian adults).

• Glucose-galactose malabsorption — rare genetic defect in SGLT-1 → severe watery diarrhoea in neonates • Oral Rehydration Salts (ORS) work because glucose + Na⁺ co-transport via SGLT-1 drives water absorption — the most important pharmacological application of carbohydrate.

• Oral Rehydration Salts (ORS) work because glucose + Na⁺ co-transport via SGLT-1 drives water absorption — the most important pharmacological application of carbohydrate transport

Glycolysis (Greek: glyco = sweet, lysis = splitting) is the pathway that converts one molecule of glucose (6C) into two molecules of pyruvate (3C), generating ATP and NADH.

It occurs in the cytoplasm of every cell — no mitochondria needed.

Glycolysis has two phases: Phase 1: Energy Investment (steps 1–5) — you SPEND 2 ATP The logic: glucose is a stable molecule.

Phase 1: Energy Investment (steps 1–5) — you SPEND 2 ATP The logic: glucose is a stable molecule.

• Step 1: Glucose → Glucose-6-phosphate (G6P).

Enzyme: hexokinase (or glucokinase in the liver).

Enzyme: hexokinase (or glucokinase in the liver).

• Step 3: Fructose-6-phosphate → Fructose-1,6-bisphosphate.

Enzyme: phosphofructokinase-1 (PFK-1).

Glycolysis (Greek: glyco = sweet, lysis = splitting) is the pathway that converts one molecule of glucose (6C) into two molecules of pyruvate (3C), generating ATP and NADH.

• Step 4: The 6-carbon fructose-1,6-bisphosphate is split into two 3-carbon molecules: DHAP and glyceraldehyde-3-phosphate (G3P).

• Step 4: The 6-carbon fructose-1,6-bisphosphate is split into two 3-carbon molecules: DHAP and glyceraldehyde-3-phosphate (G3P).

From here on, everything happens twice (once for each 3C fragment).

Phase 2: Energy Payoff (steps 6–10) — you EARN 4 ATP + 2 NADH The logic: now you extract the energy.

Each 3C fragment is oxidised (loses electrons to NAD⁺ → NADH) and its phosphate groups are transferred to ADP → ATP.

• Step 6: G3P is oxidised and phosphorylated → 1,3-bisphosphoglycerate.

• Step 7: Substrate-level phosphorylation — the high-energy phosphate is transferred directly to ADP → ATP.

NET YIELD of glycolysis: 2 ATP + 2 NADH + 2 pyruvate (per glucose) (Gross: 4 ATP earned − 2 ATP invested = 2 ATP net) What happens to pyruvate?

(Gross: 4 ATP earned − 2 ATP invested = 2 ATP net) What happens to pyruvate?

What happens to pyruvate? • With oxygen (aerobic): Pyruvate enters mitochondria → pyruvate dehydrogenase converts it to acetyl-CoA → enters the TCA cycle → full oxidation → 30-32 total ATP per glucose • Without oxygen (anaerobic): Pyruvate → lactate (via lactate dehydrogenase,.

• With oxygen (aerobic): Pyruvate enters mitochondria → pyruvate dehydrogenase converts it to acetyl-CoA → enters the TCA cycle → full oxidation → 30-32 total ATP per glucose • Without oxygen (anaerobic): Pyruvate → lactate (via lactate dehydrogenase, regenerating NAD⁺).

• With oxygen (aerobic): Pyruvate enters mitochondria → pyruvate dehydrogenase converts it to acetyl-CoA → enters the TCA cycle → full oxidation → 30-32 total ATP per glucose • Without oxygen (anaerobic): Pyruvate → lactate (via lactate dehydrogenase, regenerating NAD⁺).

• With oxygen (aerobic): Pyruvate enters mitochondria → pyruvate dehydrogenase converts it to acetyl-CoA → enters the TCA cycle → full oxidation → 30-32 total ATP per glucose • Without oxygen (anaerobic): Pyruvate → lactate (via lactate dehydrogenase, regenerating NAD⁺).

• Without oxygen (anaerobic): Pyruvate → lactate (via lactate dehydrogenase, regenerating NAD⁺).

• Without oxygen (anaerobic): Pyruvate → lactate (via lactate dehydrogenase, regenerating NAD⁺).

Regulation of glycolysis — three irreversible steps, three regulatory enzymes: 1.

Enzyme: phosphofructokinase-1 (PFK-1).

Pyruvate kinase (step 10) — stimulated by F-1,6-BP (feedforward activation).

*Why is this clinically important?* Glycolysis is the ONLY pathway for ATP production in red blood cells (no mitochondria), the lens of the eye, and the renal medulla.

*Why is this clinically important?* Glycolysis is the ONLY pathway for ATP production in red blood cells (no mitochondria), the lens of the eye, and the renal medulla.

*Why is this clinically important?* Glycolysis is the ONLY pathway for ATP production in red blood cells (no mitochondria), the lens of the eye, and the renal medulla.

Cancer cells also rely heavily on glycolysis even in the presence of oxygen — the Warburg effect — which is the basis of PET scans (cancer cells take up more glucose).

The tricarboxylic acid (TCA) cycle (also called the Krebs cycle or citric acid cycle) is the final common pathway for the oxidation of carbohydrates, fats, and proteins.

The tricarboxylic acid (TCA) cycle (also called the Krebs cycle or citric acid cycle) is the final common pathway for the oxidation of carbohydrates, fats, and proteins.

The tricarboxylic acid (TCA) cycle (also called the Krebs cycle or citric acid cycle) is the final common pathway for the oxidation of carbohydrates, fats, and proteins.

It occurs in the mitochondrial matrix.

The key steps (understand the logic, not the structures): • Step 1: Acetyl-CoA + Oxaloacetate → Citrate (6C).

• Step 1: Acetyl-CoA + Oxaloacetate → Citrate (6C).

Enzyme: citrate synthase.

• Steps 3-4: Two decarboxylation reactions release 2 CO₂ (this is where the carbon is lost — the CO₂ you exhale!).

- Isocitrate → α-ketoglutarate (enzyme: isocitrate dehydrogenase — __rate-limiting step__).

- α-ketoglutarate → succinyl-CoA (enzyme: α-ketoglutarate dehydrogenase).

• Step 5: Substrate-level phosphorylation — succinyl-CoA → succinate.

The energy is captured as NADH, FADH₂, and GTP.

• Steps 6-8: Regeneration of oxaloacetate — succinate is oxidised back to oxaloacetate through fumarate and malate.

Net yield per acetyl-CoA (one turn): 3 NADH + 1 FADH₂ + 1 GTP + 2 CO₂ Per glucose (two turns, since 1 glucose → 2 acetyl-CoA): 6 NADH + 2 FADH₂ + 2 GTP + 4 CO₂ *Where does the ATP come from?* The NADH and FADH₂ carry electrons to the electron transport chain (ETC) on the inner.

Per glucose (two turns, since 1 glucose → 2 acetyl-CoA): 6 NADH + 2 FADH₂ + 2 GTP + 4 CO₂ *Where does the ATP come from?* The NADH and FADH₂ carry electrons to the electron transport chain (ETC) on the inner mitochondrial membrane.

*Where does the ATP come from?* The NADH and FADH₂ carry electrons to the electron transport chain (ETC) on the inner mitochondrial membrane.

Total ATP per glucose (complete oxidation): | Stage | ATP (or equivalent) | |-------|---------------------| | Glycolysis | 2 ATP + 2 NADH (→5 ATP) | | Pyruvate dehydrogenase (×2) | 2 NADH (→5 ATP) | | TCA cycle (×2) | 6 NADH (→15 ATP) + 2 FADH₂ (→3 ATP) + 2 GTP | | TOTAL |.

| TOTAL | ~30-32 ATP | Regulation: The TCA cycle is regulated by energy charge and substrate availability: • Stimulated by: ADP (low energy), NAD⁺, Ca²⁺ • Inhibited by: ATP (high energy), NADH, citrate, succinyl-CoA *Remember:* The TCA cycle doesn't just burn carbohydrates.

| TOTAL | ~30-32 ATP | Regulation: The TCA cycle is regulated by energy charge and substrate availability: • Stimulated by: ADP (low energy), NAD⁺, Ca²⁺ • Inhibited by: ATP (high energy), NADH, citrate, succinyl-CoA *Remember:* The TCA cycle doesn't just burn carbohydrates.

Regulation: The TCA cycle is regulated by energy charge and substrate availability: • Stimulated by: ADP (low energy), NAD⁺, Ca²⁺ • Inhibited by: ATP (high energy), NADH, citrate, succinyl-CoA *Remember:* The TCA cycle doesn't just burn carbohydrates.

• Stimulated by: ADP (low energy), NAD⁺, Ca²⁺ • Inhibited by: ATP (high energy), NADH, citrate, succinyl-CoA *Remember:* The TCA cycle doesn't just burn carbohydrates.

• Inhibited by: ATP (high energy), NADH, citrate, succinyl-CoA *Remember:* The TCA cycle doesn't just burn carbohydrates.

Gluconeogenesis = synthesis of NEW glucose from non-carbohydrate precursors.

It occurs primarily in the liver (90%) and to a lesser extent in the kidney (10%), mainly in the cytoplasm (with some mitochondrial steps).

*When does your body need this?* During fasting (after liver glycogen is depleted, ~12-18 hours), starvation, and prolonged exercise.

*When does your body need this?* During fasting (after liver glycogen is depleted, ~12-18 hours), starvation, and prolonged exercise.

*When does your body need this?* During fasting (after liver glycogen is depleted, ~12-18 hours), starvation, and prolonged exercise.

Precursors (non-carbohydrate sources of glucose): • Lactate — from anaerobic glycolysis in RBCs and exercising muscle → carried to liver → converted back to glucose.

This is the Cori cycle (lactate → liver → glucose → blood → muscle → lactate → repeat) • Glycerol — from breakdown of triglycerides (fat stores) • Glucogenic amino acids — especially alanine (from muscle protein breakdown → carried to liver → converted to pyruvate → glucose).

• Glycerol — from breakdown of triglycerides (fat stores) • Glucogenic amino acids — especially alanine (from muscle protein breakdown → carried to liver → converted to pyruvate → glucose).

• Glucogenic amino acids — especially alanine (from muscle protein breakdown → carried to liver → converted to pyruvate → glucose).

• Glucogenic amino acids — especially alanine (from muscle protein breakdown → carried to liver → converted to pyruvate → glucose).

This is the glucose-alanine cycle • __Fatty acids CANNOT be converted to glucose__ (because acetyl-CoA cannot regenerate pyruvate — the pyruvate dehydrogenase reaction is irreversible).

Pyruvate → Oxaloacetate → Phosphoenolpyruvate (PEP): Enzymes: pyruvate carboxylase (mitochondria, requires biotin) + PEP carboxykinase (PEPCK, cytoplasm).

Pyruvate → Oxaloacetate → Phosphoenolpyruvate (PEP): Enzymes: pyruvate carboxylase (mitochondria, requires biotin) + PEP carboxykinase (PEPCK, cytoplasm).

Pyruvate → Oxaloacetate → Phosphoenolpyruvate (PEP): Enzymes: pyruvate carboxylase (mitochondria, requires biotin) + PEP carboxykinase (PEPCK, cytoplasm).

Fructose-1,6-bisphosphate → Fructose-6-phosphate: Enzyme: fructose-1,6-bisphosphatase.

Fructose-1,6-bisphosphate → Fructose-6-phosphate: Enzyme: fructose-1,6-bisphosphatase.

Glucose-6-phosphate → Glucose: Enzyme: glucose-6-phosphatase (only in liver and kidney — this is why muscle cannot release free glucose into blood; it lacks this enzyme).

Glucose-6-phosphate → Glucose: Enzyme: glucose-6-phosphatase (only in liver and kidney — this is why muscle cannot release free glucose into blood; it lacks this enzyme).

Regulation — reciprocal to glycolysis: • Fasting/glucagon → stimulates gluconeogenesis (activates PEPCK, F-1,6-BPase) and inhibits glycolysis • Fed state/insulin → stimulates glycolysis (activates PFK-1) and inhibits gluconeogenesis • Fructose-2,6-bisphosphate is the master.

• Fasting/glucagon → stimulates gluconeogenesis (activates PEPCK, F-1,6-BPase) and inhibits glycolysis • Fed state/insulin → stimulates glycolysis (activates PFK-1) and inhibits gluconeogenesis • Fructose-2,6-bisphosphate is the master switch: high F-2,6-BP activates PFK-1.

• Fed state/insulin → stimulates glycolysis (activates PFK-1) and inhibits gluconeogenesis • Fructose-2,6-bisphosphate is the master switch: high F-2,6-BP activates PFK-1 (glycolysis ON) and inhibits F-1,6-BPase (gluconeogenesis OFF).

• Fructose-2,6-bisphosphate is the master switch: high F-2,6-BP activates PFK-1 (glycolysis ON) and inhibits F-1,6-BPase (gluconeogenesis OFF).

*Clinical pearl:* Metformin, the first-line drug for type 2 diabetes, works partly by inhibiting hepatic gluconeogenesis — reducing the liver's production of glucose.

Glycogenesis (glycogen synthesis): Glucose → G6P → G1P → UDP-glucose (the activated form) → added to a glycogen primer chain by glycogen synthase (adds glucose via α-1,4 bonds).

Glucose → G6P → G1P → UDP-glucose (the activated form) → added to a glycogen primer chain by glycogen synthase (adds glucose via α-1,4 bonds).

Glucose → G6P → G1P → UDP-glucose (the activated form) → added to a glycogen primer chain by glycogen synthase (adds glucose via α-1,4 bonds).

Branching enzyme creates α-1,6 branch points every 8-12 residues.

Glycogenolysis (glycogen breakdown): Glycogen phosphorylase cleaves α-1,4 bonds from the non-reducing ends, releasing glucose-1-phosphate (G1P).

Glycogen phosphorylase cleaves α-1,4 bonds from the non-reducing ends, releasing glucose-1-phosphate (G1P).

Glycogen phosphorylase cleaves α-1,4 bonds from the non-reducing ends, releasing glucose-1-phosphate (G1P).

Debranching enzyme handles the α-1,6 branch points (releasing free glucose).

Regulation — the hormonal seesaw: • Glucagon (from pancreatic α-cells, during fasting) → activates glycogenolysis + inhibits glycogenesis in the liver.

• Glucagon (from pancreatic α-cells, during fasting) → activates glycogenolysis + inhibits glycogenesis in the liver.

• Insulin (from pancreatic β-cells, after eating) → activates glycogenesis + inhibits glycogenolysis.

• Epinephrine (adrenaline) → activates glycogenolysis in muscle (fight-or-flight: need instant glucose for sprinting).

Glycogen is your body's short-term glucose reserve — a highly branched polymer of glucose stored in liver (~100g, maintains blood glucose during fasting) and skeletal muscle (~400g, fuel for contraction).

Glycogen Storage Diseases (GSDs): These are genetic enzyme deficiencies that cause abnormal glycogen accumulation: • Von Gierke disease (GSD I) — deficiency of glucose-6-phosphatase → liver cannot release free glucose → severe fasting hypoglycaemia, hepatomegaly, lactic.

• Von Gierke disease (GSD I) — deficiency of glucose-6-phosphatase → liver cannot release free glucose → severe fasting hypoglycaemia, hepatomegaly, lactic acidosis • McArdle disease (GSD V) — deficiency of muscle glycogen phosphorylase → exercise intolerance, muscle cramps,.

• McArdle disease (GSD V) — deficiency of muscle glycogen phosphorylase → exercise intolerance, muscle cramps, myoglobinuria (no glycogen breakdown during exercise) • Pompe disease (GSD II) — deficiency of lysosomal acid maltase (α-1,4-glucosidase) → glycogen accumulates in.

• McArdle disease (GSD V) — deficiency of muscle glycogen phosphorylase → exercise intolerance, muscle cramps, myoglobinuria (no glycogen breakdown during exercise) • Pompe disease (GSD II) — deficiency of lysosomal acid maltase (α-1,4-glucosidase) → glycogen accumulates in.

• Pompe disease (GSD II) — deficiency of lysosomal acid maltase (α-1,4-glucosidase) → glycogen accumulates in lysosomes → cardiomegaly, muscle weakness, fatal in infantile form

• Pompe disease (GSD II) — deficiency of lysosomal acid maltase (α-1,4-glucosidase) → glycogen accumulates in lysosomes → cardiomegaly, muscle weakness, fatal in infantile form

Hexose Monophosphate (HMP) Shunt (= Pentose Phosphate Pathway) This alternative pathway for glucose-6-phosphate serves TWO purposes: 1.

Generates NADPH — needed for fatty acid synthesis, steroid synthesis, and maintaining reduced glutathione (protects RBCs from oxidative damage) 2.

Generates NADPH — needed for fatty acid synthesis, steroid synthesis, and maintaining reduced glutathione (protects RBCs from oxidative damage) 2.

Produces ribose-5-phosphate — needed for nucleotide synthesis (DNA and RNA) Occurs in the cytoplasm.

• Oxidative phase (irreversible): G6P → 6-phosphogluconate → ribulose-5-phosphate.

Rate-limiting enzyme: glucose-6-phosphate dehydrogenase (G6PD).

• Non-oxidative phase (reversible): Interconversions of sugars (ribose-5-phosphate ↔ fructose-6-phosphate, glyceraldehyde-3-phosphate) __G6PD deficiency__ — the most common enzyme deficiency worldwide (400 million affected, X-linked).

Without G6PD → low NADPH → low reduced glutathione → RBCs vulnerable to oxidative stress → haemolytic anaemia triggered by: • Drugs: primaquine (antimalarial), dapsone, sulfonamides • Foods: fava beans ("favism") • Infections Minor Carbohydrate Pathways (BI3.

Minor Carbohydrate Pathways (BI3.4): • Fructose metabolism — Fructose is metabolised in the liver by fructokinase → fructose-1-phosphate → cleaved by aldolase B → enters glycolysis.

• Fructose metabolism — Fructose is metabolised in the liver by fructokinase → fructose-1-phosphate → cleaved by aldolase B → enters glycolysis.

• Fructose metabolism — Fructose is metabolised in the liver by fructokinase → fructose-1-phosphate → cleaved by aldolase B → enters glycolysis.

• Fructose metabolism — Fructose is metabolised in the liver by fructokinase → fructose-1-phosphate → cleaved by aldolase B → enters glycolysis.

• Galactose metabolism — Galactose → galactose-1-phosphate → UDP-galactose → UDP-glucose → enters glycolysis.

Key enzyme: galactose-1-phosphate uridylyl transferase.

• Polyol (sorbitol) pathway — Glucose → sorbitol (by aldose reductase, using NADPH) → fructose (by sorbitol dehydrogenase).

• Polyol (sorbitol) pathway — Glucose → sorbitol (by aldose reductase, using NADPH) → fructose (by sorbitol dehydrogenase).

In diabetes, chronic hyperglycaemia drives excess sorbitol production in tissues that don't require insulin for glucose entry (lens, retina, peripheral nerves, kidneys).

Glucose homeostasis maintains fasting blood glucose at 70–100 mg/dL.

Glucose homeostasis maintains fasting blood glucose at 70–100 mg/dL.

After a meal (fed state): • Blood glucose rises → pancreatic β-cells sense this (via GLUT-2 and glucokinase) → secrete insulin • Insulin promotes: glucose uptake (GLUT-4 in muscle/fat), glycolysis, glycogenesis, lipogenesis, protein synthesis • Insulin inhibits: gluconeogenesis,.

• Blood glucose rises → pancreatic β-cells sense this (via GLUT-2 and glucokinase) → secrete insulin • Insulin promotes: glucose uptake (GLUT-4 in muscle/fat), glycolysis, glycogenesis, lipogenesis, protein synthesis • Insulin inhibits: gluconeogenesis, glycogenolysis,.

During fasting: • Blood glucose falls → pancreatic α-cells secrete glucagon • Glucagon promotes: glycogenolysis, gluconeogenesis (in liver) • Other counter-regulatory hormones also raise glucose: epinephrine, cortisol, growth hormone • Result: blood glucose maintained for brain.

• Blood glucose falls → pancreatic α-cells secrete glucagon • Glucagon promotes: glycogenolysis, gluconeogenesis (in liver) • Other counter-regulatory hormones also raise glucose: epinephrine, cortisol, growth hormone • Result: blood glucose maintained for brain.

• Other counter-regulatory hormones also raise glucose: epinephrine, cortisol, growth hormone • Result: blood glucose maintained for brain function Diabetes Mellitus — the epidemic: Type 1 DM (~5-10% of cases): • Autoimmune destruction of pancreatic β-cells → absolute insulin.

Diabetes Mellitus — the epidemic: Type 1 DM (~5-10% of cases): • Autoimmune destruction of pancreatic β-cells → absolute insulin deficiency • Onset: usually childhood/adolescence • Features: polyuria, polydipsia, weight loss, diabetic ketoacidosis (DKA) — because without.

Type 1 DM (~5-10% of cases): • Autoimmune destruction of pancreatic β-cells → absolute insulin deficiency • Onset: usually childhood/adolescence • Features: polyuria, polydipsia, weight loss, diabetic ketoacidosis (DKA) — because without insulin, fat is broken down to ketone.

• Autoimmune destruction of pancreatic β-cells → absolute insulin deficiency • Onset: usually childhood/adolescence • Features: polyuria, polydipsia, weight loss, diabetic ketoacidosis (DKA) — because without insulin, fat is broken down to ketone bodies → metabolic acidosis •.

• Features: polyuria, polydipsia, weight loss, diabetic ketoacidosis (DKA) — because without insulin, fat is broken down to ketone bodies → metabolic acidosis • Treatment: insulin replacement (lifelong) Type 2 DM (~90% of cases): • Insulin resistance + relative insulin.

Type 2 DM (~90% of cases): • Insulin resistance + relative insulin deficiency.

• Insulin resistance + relative insulin deficiency.

Biochemical complications of chronic hyperglycaemia: 1.

Non-enzymatic glycosylation (glycation) — glucose attaches to proteins → Advanced Glycation End-products (AGEs) → damage blood vessels → atherosclerosis, nephropathy, retinopathy 2.

Polyol pathway activation — excess sorbitol → osmotic damage to lens (cataracts), nerves (neuropathy) 3.

Protein Kinase C activation → vascular damage 4.

Oxidative stress → endothelial dysfunction DKA vs Hyperosmolar Hyperglycaemic State (HHS): • DKA (Type 1): glucose 300-600, ketones HIGH, pH < 7.3, anion gap metabolic acidosis.

DKA vs Hyperosmolar Hyperglycaemic State (HHS): • DKA (Type 1): glucose 300-600, ketones HIGH, pH < 7.3, anion gap metabolic acidosis.

• Features: polyuria, polydipsia, weight loss, diabetic ketoacidosis (DKA) — because without insulin, fat is broken down to ketone bodies → metabolic acidosis • Treatment: insulin replacement (lifelong) Type 2 DM (~90% of cases): • Insulin resistance + relative insulin.

DKA vs Hyperosmolar Hyperglycaemic State (HHS): • DKA (Type 1): glucose 300-600, ketones HIGH, pH < 7.3, anion gap metabolic acidosis.

1. Fasting Plasma Glucose (FPG) • Normal: < 100 mg/dL • Impaired fasting glucose (pre-diabetes): 100–125 mg/dL • Diabetes: ≥ 126 mg/dL (confirmed on two occasions) • *Why fasting?* Eliminates the post-meal glucose spike.

2. Oral Glucose Tolerance Test (OGTT) • Patient drinks 75g glucose in water.

3. HbA1c (Glycated Haemoglobin) • Measures average blood glucose over the past 2-3 months (lifespan of RBCs) • Normal: < 5.7% • Pre-diabetes: 5.7–6.4% • Diabetes: ≥ 6.

• Measures average blood glucose over the past 2-3 months (lifespan of RBCs) • Normal: < 5.7% • Pre-diabetes: 5.7–6.4% • Diabetes: ≥ 6.

4. Random Plasma Glucose • ≥ 200 mg/dL with classic symptoms (polyuria, polydipsia, weight loss) = diagnostic of DM 5.

5. Blood Ketones / Urine Ketones • Elevated in DKA (β-hydroxybutyrate > acetoacetate > acetone) • Urine dipstick detects acetoacetate (may underestimate severity if β-hydroxybutyrate is predominant) • Blood β-hydroxybutyrate > 3 mmol/L = significant ketosis 6.

6. Blood Lactate • Normal: 0.5–1.5 mmol/L.

7. Reducing sugar tests (urine) • Benedict's test — detects any reducing sugar (glucose, galactose, fructose, lactose) • Glucose oxidase test (dipstick) — specific for glucose only • If Benedict's positive but glucose oxidase negative → non-glucose reducing sugar → think.

• Benedict's test — detects any reducing sugar (glucose, galactose, fructose, lactose) • Glucose oxidase test (dipstick) — specific for glucose only • If Benedict's positive but glucose oxidase negative → non-glucose reducing sugar → think galactosaemia (galactose) or hereditary.

• Glucose oxidase test (dipstick) — specific for glucose only • If Benedict's positive but glucose oxidase negative → non-glucose reducing sugar → think galactosaemia (galactose) or hereditary fructose intolerance (fructose) Interpreting results together — a clinical.

Interpreting results together — a clinical framework: High fasting glucose + high HbA1c = poorly controlled diabetes.

In rare cases (especially in renal impairment), metformin can cause lactic acidosis — lactate cannot be converted to glucose (gluconeogenesis blocked) → accumulates.

Trace the glucose molecule: You eat a roti.

The 24-hour fast: A medical student skips dinner and breakfast (18-hour fast).

DKA vs HHS: A Type 1 diabetic (22 years old) and a Type 2 diabetic (65 years old) both present with blood glucose > 500 mg/dL.

The lab puzzle: A neonate has a positive Benedict's test (reducing sugar in urine) but NEGATIVE glucose oxidase test.

Cross-subject connection: Red blood cells have no mitochondria.

Key takeaways — your study checklist: 1.

Classification (BI3.1): Monosaccharides (glucose, fructose, galactose), disaccharides (sucrose, lactose, maltose), polysaccharides (starch, glycogen, cellulose, GAGs).

Digestion & absorption (BI3.2): Salivary amylase → pancreatic amylase → brush border enzymes (maltase, sucrase, lactase).

Glycolysis (BI3.3): 10 steps, 2 phases.

TCA cycle (BI3.3): Mitochondrial matrix.

Gluconeogenesis (BI3.3): Liver/kidney.

Glycogen metabolism (BI3.3): Synthesis (glycogen synthase), breakdown (glycogen phosphorylase).

HMP shunt (BI3.3): Produces NADPH + ribose-5-phosphate.

Minor pathways (BI3.4): Fructose metabolism (aldolase B deficiency → HFI), galactose metabolism (transferase deficiency → galactosaemia), polyol pathway (diabetic complications — cataracts, neuropathy).

Glucose homeostasis (BI3.5): Insulin (lowers) vs glucagon (raises).

Lab investigations (BI3.6): FPG (≥126 = DM), OGTT (≥200 at 2h), HbA1c (≥6.5%), lactate (anaerobic glycolysis marker), Benedict's vs glucose oxidase (non-glucose reducing sugars → galactosaemia).