Carbohydrates: Classification, Monosaccharides, and Bonds

• Carbohydrates are organic molecules of carbon, hydrogen, and oxygen with the formula CnH2nOn and function as a major energy source and have structural roles

Classification of Carbohydrates

• Monosaccharides are single sugar units like glucose, fructose, and galactose
• Oligosaccharides consist of 2-10 monosaccharides linked by glycosidic bonds, found in disaccharides like sucrose, lactose and maltose
• Polysaccharides have more than 10 monosaccharide units, including starch, glycogen, and cellulose
• A monosaccharide is the simplest carbohydrate and cannot be hydrolyzed into simpler sugars
• A glycosidic bond is a covalent bond between a sugar's anomeric carbon and the hydroxyl group of another molecule

Monosaccharides

• Monosaccharides have a general formula of CnH2nOn, with C6H12O6 common for glucose and related sugars
• Functional groups can be either an aldehyde group (aldose) or a ketone group (ketose)
• Glucose is an aldohexose (6-carbon aldehyde sugar) with the anomeric carbon being C-1 in the ring form (pyranose)
• Fructose is a ketohexose (6-carbon ketone sugar), where the anomeric carbon is C-2 in the ring form (furanose)
• Galactose is an aldohexose and an epimer of glucose at carbon-4
• Mannose is an aldohexose and an epimer of glucose at carbon-2
• An aldose is a monosaccharide with an aldehyde (-CHO) group
• A ketose is a monosaccharide with a ketone (-C=O) group
• The anomeric carbon is the carbonyl carbon (C=O) in the linear form of a monosaccharide that becomes a new chiral center in the ring form.
• D and L isomers depend on the configuration around the chiral carbon farthest from the aldehyde/ketone group, with most naturally sugars being in the D-form
• Epimers differ in configuration around one specific carbon
• Anomers differ in configuration around the anomeric carbon forming α or β ring structures
• Isomers are compounds that share the same molecular formula but differ in structural arrangements

Disaccharides

• Disaccharides are formed by a glycosidic bond between the hydroxyl group of one monosaccharide and the anomeric carbon of another
• Sucrose is composed of glucose and fructose
• Lactose is composed of glucose and galactose
• Maltose is composed of glucose and glucose
• A disaccharide is a carbohydrate of two monosaccharides linked by a glycosidic bond

Polysaccharides

• Starch is the main storage polysaccharide in plants, consisting of amylose (α-1,4 link) and amylopectin (α-1,4 and α-1,6 linkages)
• Glycogen is the main storage in animals, similar to amylopectin but more highly branched (α-1,4 and α-1,6 linkages)
• Cellulose is a structural polysaccharide in plants with β-1,4 linkages that humans cannot digest
• A polysaccharide is a complex carbohydrate made of many monosaccharide units linked via glycosidic bonds

Digestion

• Salivary α-amylase starts hydrolyzing α-1,4 glycosidic bonds in starch in the mouth
• A low pH inactivates salivary amylase in the stomach, resulting in little carbohydrate digestion
• Pancreatic α-amylase continues digesting starch to maltose, maltotriose, and small oligosaccharides in the small intestine
• Brush border enzymes break disaccharides into monosaccharides
• Amylase is an enzyme that catalyzes the hydrolysis of starch

Absorption

• Carbohydrates are mainly absorbed in the small intestine (jejunum)
• Glucose and galactose use active transport with SGLT1
• Fructose uses facilitated diffusion via GLUT5
• All monosaccharides exit enterocytes into the bloodstream via GLUT2
• Active transport requires ATP to move molecules against their concentration gradient
• Facilitated diffusion down the concentration gradient works via transporter proteins and does not require ATP

Glycolysis

• Glycolysis occurs in the cytoplasm of all cells
• Key steps include: Glucose to Glucose-6-phosphate via Hexokinase/Glucokinase; Fructose-6-phosphate to Fructose-1,6-bisphosphate via Phosphofructokinase-1 (PFK-1 as the key regulatory enzyme); Glyceraldehyde-3-phosphate to 1,3-Bisphosphoglycerate via G3P dehydrogenase; Phosphoenolpyruvate to Pyruvate via Pyruvate kinase
• Products of glycolysis yield 2 pyruvate, net 2 ATP, and 2 NADH per glucose under aerobic conditions
• Glycolysis turns glucose (6C) into pyruvate (3C) with ATP and NADH

Pyruvate Oxidation and TCA Cycle

• Pyruvate (3C) is converted to Acetyl-CoA (2C) by the Pyruvate Dehydrogenase Complex (in mitochondria), producing NADH and CO2
• Acetyl-CoA enters the TCA cycle (Citric Acid Cycle)
• A series of enzyme-catalyzed reactions in the mitochondrial matrix oxidize Acetyl-CoA to CO2, generating reduced coenzymes (NADH, FADH2) and GTP/ATP

Oxidative Phosphorylation

• NADH and FADH2 produced feed electrons into the electron transport chain (mitochondrial inner membrane)
• A proton gradient results, leading to ATP synthesis via ATP synthase
• Oxidative phosphorylation is the process in which energy from electron transfer (via the electron transport chain) pumps protons across the mitochondrial membrane to drive ATP production

Gluconeogenesis

• Gluconeogenesis mainly happens in the liver and to some extent in the kidney cortex
• Key substrates include lactate, glycerol, and glucogenic amino acids
• Key enzymes include: Pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase, glucose-6-phosphatase
• Gluconeogenesis is an anabolic pathway that synthesizes glucose from non-carbohydrate precursors and ensures glucose availability during fasting

Glycogenesis and Glycogenolysis

• Glycogenesis is the synthesis of glycogen, driven by glycogen synthase
• Glycogenolysis is the breakdown of glycogen, by glycogen phosphorylase
• Glycogen is a branched polysaccharide of glucose which functions as the main storage form of carbohydrate in animals

Pentose Phosphate Pathway (HMP Shunt)

• Produces NADPH for reductive biosynthesis, protection against oxidative stress and ribose-5-phosphate for nucleotide synthesis
• NADPH is a coenzyme involved in anabolic reactions, maintains the reducing environment of cells, and protects against oxidative damage

Definition (Lipids)

• Lipids are hydrophobic/amphipathic molecules, including fats, oils, waxes, phospholipids, and steroids, and are composed of carbon and hydrogen, with fewer oxygen atoms

Lipids Classification

• Fatty Acids (FAs) are either saturated (no double bonds) or unsaturated (one or more double bonds)
• Triacylglycerols (Triglycerides) contain a a glycerol backbone and 3 fatty acids (ester linkages); this is the main storage form of lipids in adipose tissue
• Phospholipids contain a phosphate group, in addition to fatty acid chains
• Glycolipids contain a carbohydrate component
• Steroids have a fused ring structure with molecules such as cholesterol and steroid hormones

Fatty Acids

• Fatty acids has a structure of carboxylic acid group (-COOH) and a hydrocarbon chain
• Essential Fatty Acids are linoleic acid (ω-6) and α-linolenic acid (ω-3) that the body cannot synthesize and they must come from the diet

Phospholipids

• Phospholipids has a general structure of glycerol backbone, 2 fatty acid chains (at C-1 and C-2 of glycerol), and a phosphate group
• Examples include Phosphatidylcholine (Lecithin): Glycerol + 2 FAs + phosphate + choline, Phosphatidylethanolamine, Phosphatidylserine, Phosphatidylinositol
• A phospholipid is a lipid that contains a phosphate group, making it amphipathic with hydrophobic tails and a hydrophilic head

Prostaglandins (Eicosanoids)

• Prostaglandins are derived from Arachidonic acid (20:4 ω-6)
• Prostaglandins, thromboxanes and leukotrienes (LTs) are all included
• Prostaglandins function in inflammatory response, platelet aggregation, and gastric acid secretion regulation
• Prostaglandins are one class of eicosanoids (signaling molecules) produced by the oxidation of 20-carbon essential fatty acids with involvement in physiological and pathological processes

Lipid Digestion and Absorption

• A minor role of lingual and gastric lipases begins digestion (particularly short-chain fats in infants) in the mouth and stomach
• Bile salts emulsify dietary fats, increasing surface area in the small intestine
• Pancreatic lipase hydrolyzes triacylglycerols into 2-monoacylglycerols and free fatty acids
• Cholesterol esterase and phospholipase A2 breaks down cholesterol esters and phospholipids, respectively, in the small intestine
• Emulsification in lipids is the process of breaking large fat droplets into smaller micelles, increasing surface area for enzyme action

Absorption

• Micelles formed by bile salts carry fatty acids, monoacylglycerols, and cholesterol to the intestinal brush border
• Lipids enter enterocytes, where they are re-esterified, then packaged into chylomicrons
• Chylomicrons enter the lymphatic system, and then the bloodstream
• A chylomicron is a lipoprotein particle in intestinal cells to transport lipids

Lipid Metabolism

• Chylomicrons transport dietary triglycerides and cholesterol from the intestine to tissues
• VLDL, LDL, and HDL transport triglycerides and cholesterol and participate in reverse cholesterol transport
• Lipoproteins are complexes of lipids and proteins that allow fats to move through the water-based bloodstream

Fatty Acid Oxidation (β-Oxidation)

• Fatty acid oxidation happens in the mitochondrial matrix
• Repetitive removal of 2-carbon units as acetyl-CoA produces FADH2 and NADH
• Regulation of fatty acid oxidation happens when Malonyl-CoA inhibits carnitine acyltransferase I (CAT I), controlling entry of FAs into mitochondria
• β-Oxidation is the catabolic process by which fatty acid molecules are broken down in the mitochondria to generate acetyl-CoA, NADH, and FADH2

Ketone bodies

• Synthesized in the liver from excess acetyl-CoA when carbohydrate availability is low in starvation and untreated diabetes
• Ketone bodies are acetoacetate, β-hydroxybutyrate, and acetone
• Peripheral tissues can convert ketone bodies back to acetyl-CoA for energy.
• Ketone bodies are water-soluble, produced by the liver from fatty acids during periods of low carbohydrate availability, and can be used as an alternative energy source

Fatty Acid Synthesis (Lipogenesis)

• Lipogenesis happens in the cytoplasm of the liver and adipose tissue
• Acetyl-CoA carboxylase (ACC) converts acetyl-CoA to malonyl-CoA, which is the rate-limiting step
• Fatty Acid Synthase uses malonyl-CoA and acetyl-CoA to form palmitate
• Insulin activates ACC, while Glucagon inhibits ACC, regulating Lipogenesis
• Lipogenesis synthesizes fatty acids from acetyl-CoA and malonyl-CoA in the cytosol and is particularly active in the fed state.

Cholesterol Metabolism

• Cholesterol Biosynthesis primarily happens in the liver and starts from acetyl-CoA
• The rate-limiting step is HMG-CoA reductase
• Cholesterol can be used to make bile acids/salts, steroid hormones; synthesize vitamin D; and incorporate into membranes
• Cholesterol is a sterol essential for cell membrane fluidity, is a precursor of steroid hormones and bile acids, and is used in vitamin D synthesis

Lipidoses (lipid storage diseases)

• Lipidoses are rare and inherited metabolic disorders characterized by the accumulation of lipids due to enzyme deficiencies
• Tay-Sachs Disease has a deficient enzyme of Hexosaminidase A with an accumulation of GM2 ganglioside and a clinical feature of neurodegeneration as well as a cherry-red spot on the macula
• Gaucher's Disease has a deficient enzyme of Glucocerebrosidase (β-glucosidase) with an accumulation of Glucocerebroside
• Niemann-Pick Disease has a deficient enzyme of Sphingomyelinase with an accumulation of Sphingomyelin
• Metachromatic Leukodystrophy has a deficient enzyme of Arylsulfatase A with an accumulation of Cerebroside sulfate
• Krabbe Disease has a deficient enzyme of Galactocerebrosidase with an accumulation of Galactocerebroside and psychosine
• Lipidoses are a group of inherited disorders involving defective enzymes responsible for lipid metabolism, causing abnormal accumulation of lipids in cells

Explore the classification and structure of carbohydrates, including monosaccharides, oligosaccharides, and polysaccharides. Learn about glycosidic bonds and delve into monosaccharides, their formulas, and functional groups such as aldoses and ketoses. Understand the role and importance of carbohydrates.