Carbohydrates: Fuel and Structure

Carbohydrates are organic molecules composed of carbon, hydrogen, and oxygen, typically in the ratio (CH₂O)n. The name literally means "carbon hydrate" — carbon plus water. They are the body's primary and preferred fuel source, and also play structural roles (in cell walls, connective tissue, and cell surface markers). Three sizes of carbohydrates: 1. Monosaccharides — the simple sugars The building blocks. Cannot be broken down further. Key examples: - Glucose — the body's main fuel. All carbohydrates are ultimately converted to glucose for energy production - Fructose — found in fruit; sweeter than glucose. Metabolised primarily in the liver - Galactose — found in dairy (as part of lactose). Converted to glucose in the liver 2. Disaccharides — two monosaccharides linked Formed by a glycosidic bond with loss of water (condensation reaction): - Sucrose (glucose + fructose) — table sugar - Lactose (glucose + galactose) — milk sugar. Lactase deficiency causes lactose intolerance — undigested lactose reaches the colon, where bacteria ferment it → bloating, cramping, diarrhoea - Maltose (glucose + glucose) — found in germinating grains and as a digestion product of starch 3. Polysaccharides — many monosaccharides linked - Starch — the storage form in plants (potatoes, rice, bread). Digested by amylase → glucose - Glycogen — the storage form in animals. Stored in liver (releases glucose into blood) and muscle (local fuel). Highly branched for rapid mobilisation - Cellulose — plant cell wall structural polysaccharide. Cannot be digested by humans (no cellulase enzyme) — passes through as dietary fibre

Blood glucose is maintained at 4–6 mmol/L by an exquisitely sensitive feedback system — even small deviations have serious consequences. After eating (postprandial state): Glucose absorbed from the gut → blood glucose rises → pancreatic beta cells release insulin → insulin: - Promotes glucose uptake into muscle and fat cells (via GLUT4 transporters) - Stimulates glycogenesis (glucose → glycogen storage) in liver and muscle - Stimulates protein synthesis - Promotes fat storage (lipogenesis) - Inhibits glycogen breakdown and gluconeogenesis During fasting: Blood glucose falls → pancreatic alpha cells release glucagon → glucagon: - Stimulates glycogenolysis (glycogen → glucose) in the liver - Stimulates gluconeogenesis (making new glucose from amino acids, lactate, glycerol) in the liver - Mobilises fatty acids from fat stores as an alternative fuel Key glycolysis connection: Glucose → 2 pyruvate via glycolysis (cytoplasm). If oxygen is available, pyruvate → acetyl-CoA → Krebs cycle + ETC → ~32 ATP. If no oxygen, pyruvate → lactate (anaerobic, only 2 ATP). This is why muscle burns during intense exercise — oxygen cannot keep up, so anaerobic glycolysis produces lactic acid. Glycogen storage diseases: Inherited defects in glycogen metabolism enzymes cause glycogen to accumulate abnormally in tissues. Von Gierke disease (glucose-6-phosphatase deficiency) — severe hypoglycaemia on fasting; the liver is packed with glycogen but cannot release glucose. McArdle disease (muscle glycogen phosphorylase deficiency) — muscle cramps and weakness on exercise; muscle cannot mobilise its glycogen for energy.

Diabetes mellitus is defined as chronic hyperglycaemia (elevated blood glucose) due to defects in insulin secretion, insulin action, or both. It is one of the most common and costly chronic diseases worldwide. Type 1 Diabetes (T1DM): Autoimmune destruction of pancreatic beta cells → absolute insulin deficiency. Typically presents in childhood or young adulthood with rapid onset. Features: polyuria, polydipsia, weight loss, and life-threatening diabetic ketoacidosis (DKA) if untreated. Treatment: lifelong insulin replacement. Type 2 Diabetes (T2DM): Cells become resistant to insulin → pancreas compensates by making more → eventually beta cells exhaust. Strongly associated with obesity (excess fat causes inflammation and impaired insulin receptor signalling). Gradual onset, often asymptomatic for years. Complications develop silently. Treatment: lifestyle modification, metformin, various oral agents, eventually insulin. Diagnosing diabetes (WHO criteria): - Fasting plasma glucose ≥7.0 mmol/L, OR - Random plasma glucose ≥11.1 mmol/L with symptoms, OR - HbA1c ≥48 mmol/mol (6.5%) HbA1c — the 3-month average: Glucose spontaneously attaches to haemoglobin in red blood cells (glycation) in proportion to blood glucose levels. Since red blood cells live ~120 days, HbA1c reflects average blood glucose over the past 3 months. It is the gold standard for monitoring long-term diabetes control — not affected by meals or stress on the day of testing. Complications of chronic hyperglycaemia: High glucose glycates proteins and damages blood vessels — causing: - Microvascular (small vessels): retinopathy (blindness), nephropathy (kidney failure), peripheral neuropathy (foot pain, ulcers) - Macrovascular (large vessels): heart attacks, strokes, peripheral arterial disease - Tight glucose control (HbA1c <53 mmol/mol) significantly reduces complication risk

Not all carbohydrates are fuel — many serve critical structural and signalling roles. Glycoproteins and glycolipids: Many proteins and lipids on the cell surface have carbohydrate chains attached — forming glycoproteins and glycolipids. Together, these form the glycocalyx — a sugar-rich coat on the outer surface of every cell in the body. The glycocalyx serves several functions: - Cell-cell recognition — allows cells to identify each other (essential for immune function, development, and tissue organisation) - Adhesion — helps cells stick to each other and to the extracellular matrix - Protection — acts as a physical barrier and lubricant - Receptor function — many signalling molecules bind glycoproteins on the cell surface Blood groups — the ABO system: Blood groups are determined by specific sugar structures on the surface of red blood cells: - Type A — has A antigens (terminal N-acetylgalactosamine on the sugar chain) - Type B — has B antigens (terminal galactose) - Type AB — has both; universal recipient for red blood cells - Type O — has neither A nor B antigens; universal donor for red blood cells The immune system makes antibodies against the blood group antigens it does NOT have — which is why giving type A blood to a type B patient triggers a life-threatening transfusion reaction. Collagen — the body's structural scaffold: Collagen is the most abundant protein in the body (30% of total protein), and its biosynthesis requires carbohydrate modifications. Each collagen molecule is a triple helix of three polypeptide chains. Vitamin C (ascorbic acid) is essential for hydroxylation of proline residues in collagen synthesis — without it, collagen cannot form proper triple helices, causing scurvy: bleeding gums, poor wound healing, fragile blood vessels. Scurvy was historically devastating in sailors deprived of fresh fruit for months at sea.

Dietary fibre refers to carbohydrates that cannot be digested by human enzymes — mainly plant cell wall polysaccharides (cellulose, hemicellulose, pectin) and resistant starch. Since they pass undigested into the large intestine, they are not a direct energy source for humans. However, the trillions of bacteria in the large intestine (the gut microbiome) ferment dietary fibre, producing: - Short-chain fatty acids (SCFAs) — acetate, propionate, and butyrate. These are absorbed by the colon wall and provide about 10% of daily caloric needs. Butyrate is particularly important as the main energy source for colonocytes (colon lining cells) - Gases — CO₂, methane, hydrogen — which cause flatulence when fibre intake increases suddenly - Various vitamins (particularly vitamin K and some B vitamins) Why fibre matters for health: - Slows glucose absorption — soluble fibre (oats, beans, apples) forms a gel that slows digestion, reducing post-meal blood glucose spikes — beneficial in diabetes - Lowers LDL cholesterol — soluble fibre binds bile acids in the gut and prevents their reabsorption → liver must use cholesterol to make more bile acids → blood LDL falls - Feeds beneficial bacteria — a diverse fibre intake promotes a diverse, healthy microbiome, linked to reduced obesity, type 2 diabetes, colorectal cancer, and inflammatory bowel disease risk - Bowel regularity — insoluble fibre (wheat bran) adds bulk to stools, preventing constipation The glycaemic index (GI): Measures how quickly a food raises blood glucose compared to pure glucose (GI = 100). White bread = GI ~75; rolled oats = GI ~55; lentils = GI ~30. Lower GI foods release glucose slowly, causing smaller insulin spikes — better for blood glucose control in diabetes and weight management.