Gluconeogenesis Mechanisms

Metabolic Pathways

• Neoglucogenesis cycle recycles lactate (from muscles and RBCs) and glycerol (from adipose tissue) into glucose.
• Takes place predominantly in the liver and kidneys' cortex.
• Activated under low carbohydrate intake to fulfill glucose needs.

Hormonal Regulation

• Glucagon, secreted by pancreatic α-cells, plays a crucial role in increasing blood glucose levels.
• Regulates conversion between fructose 1,6-bisphosphate and fructose 6-phosphate, promoting gluconeogenesis.

Glycogenesis

• Glycogenesis is the conversion of glucose into glycogen for storage in the liver and muscles.
• Essential for blood sugar maintenance and immediate energy supply during fasting.
• Liver glycogen acts as a reservoir for the entire body; muscle glycogen provides local energy for muscle contraction.

Glycogenesis Regulation

• Insulin stimulates glycogenesis by activating glycogen synthase and inhibiting glycogenolysis.
• Glucagon stimulates glycogenolysis while inhibiting glycogenesis.
• Adrenaline triggers glycogenolysis in muscle cells for quick energy release during stress.
• Allosteric regulation involves glucose-6-phosphate, which can activate glycogen synthase.

Glycogenolysis

• Glycogenolysis is the breakdown of glycogen to release glucose, primarily occurring in the liver and kidneys.
• In muscle cells, it produces glucose-6-phosphate for local energy requirements.

Glucose Measurement

• Glucose oxidase enzyme converts glucose to gluconic acid and hydrogen peroxide; detection methods involve photometric or electrical analysis.
• Test methods include Testape for urine glucose and Dextrostix for blood glucose.

Esterification Reactions

• Hydroxyl groups in sugars can react with acids, forming phosphate esters, key intermediates in carbohydrate breakdown.

Reduction and Sugar Alcohols

• Aldehydes can be reduced to primary alcohols, producing sugar alcohols like sorbitol, a common food and cosmetic moisturizing agent.

Glycolysis

• Glycolysis is the breakdown of glucose to produce energy (pyruvate, ATP, NADH) occurring in the cytoplasm without oxygen.

Gluconeogenesis

• Gluconeogenesis synthesizes glucose from non-carbohydrate sources (amino acids, lactate), vital during fasting.

Carbohydrate Structures

• Sugars can be represented in straight chain (Fischer projections) or cyclic forms (Haworth projections).
• D- and L-sugars are enantiomers with different optical rotations.

Chirality

• Chiral centers have four distinct groups bonded to an atom; chiral molecules cannot superimpose their mirror images.

Monosaccharide Classification

• Monosaccharides classified as aldoses or ketoses depending on functional groups, further divided based on carbon count (trioses to hexoses).

D-Glucose

• D-Glucose, also known as blood sugar, is the most abundant and critical for human metabolism, found in ripe fruits.

Use of Monosaccharides

• 50% glucose solution is hypertonic, utilized in medical treatment to restore blood glucose levels, especially in hypoglycemia.

Starch and Cellulose

• Starch consists of amylose and amylopectin; iodine testing yields a blue color indicative of starch presence.
• Cellulose, a linear homopolymer of β-D-glucose, contributes to plant fiber strength.

Lactose

• Lactose, or milk sugar, is produced in mammalian glands from glucose, occurring in a mix of α and β forms.

Disaccharides

• Maltose, formed from starch hydrolysis, is linked by a α(1→4) glycosidic bond and useful in baby foods and other products.

Health Note

• Lactose intolerance causes digestive issues in some individuals due to insufficient β-galactosidase enzyme, affecting milk consumption.

Structural Representation of Sugars

• Sugars can be represented in straight chain forms including Fischer projections and perspective structural formulas.
• D-sugars have optical rotation properties; L-amino acids do not.
• Haworth projections are more realistic representations, where substituents' orientation differs from Fischer projections.

Chirality

• A chiral center has four different substituents, leading to non-superimposable mirror images.
• Chiral molecules differ from achiral molecules, which have superimposable mirror images.

Classification and Nomenclature of Monosaccharides

• Monosaccharides are classified as aldoses (aldehyde group) or ketoses (ketone group).
• Classified further by carbon count: trioses, tetroses, pentoses, and hexoses.

D-Glucose

• Known as grape sugar, dextrose, or blood sugar; most abundant and nutritionally significant.
• Sweetness and nutritional value are high; present in ripe fruits with 20-30% glucose by mass.
• D-glucose is utilized by cells for energy, unlike L-glucose which is tasteless and non-utilizable.

Uses of Monosaccharides

• 50% glucose solution is hypertonic and useful for restoring blood glucose levels during hypoglycemia.
• No hemiacetal formation occurs due to glycosidic linkages; open-chain form is not possible.

Lactose

• Known as milk sugar, occurs naturally solely in milk.
• Enzymes synthesize lactose from glucose; comprises D-galactose and D-glucose linked by β(1-4) glycosidic linkage.
• Contains both α and β anomers in a 2:3 ratio; β-lactose is sweeter and more soluble. Souring of milk is caused by conversion to lactic acid by bacteria.

Maltose

• Also known as malt sugar, originates from starch hydrolysis by amylase.
• Found in baby food and malted milk; formed from two D-glucose residues linked by an α(1-4) glycosidic bond.

Uses of Disaccharides

• Maltose can derive from icodextrin used in dialysis.
• Sucrose is often added to medications to improve taste; Iron sucrose treats iron deficiency.

Polysaccharides

• Composed of repeating monosaccharide units linked by glycosidic bonds, releasing water during formation.
• Identifiable by monosaccharide type, polymer length, glycosidic linkage type, and branching degree.

Types and Functions of Polysaccharides

• Homoglycans include amylose (linear α-D-glucose) and amylopectin (branched α-D-glucose).
• Starch is a combination of amylose and amylopectin; glycogen resembles amylopectin but is more branched.
• Cellulose features a linear D-glucose chain with β-1,4 linkages.

Starch Characteristics

• Starch consists of polymers of D-glucose, with α-linkages found in starch and β-linkages in cellulose.
• Amylopectin has branches every 12 to 30 glucose residues; starch serves as an energy reserve in plants.

Carbohydrates in Cell Structures

• Bacterial cell walls are composed of carbohydrates; gram-positive bacteria have thick peptidoglycan walls, while gram-negative have more complex structures.
• Plant cells utilize cell walls for stability; animal cells utilize an extracellular matrix for dynamic structural needs.

Biomedical Importance of Carbohydrates

• Carbohydrates are primary energy sources, store energy, form cellular structures, and assist in molecular recognition.

Glucose Measurement Techniques

• Glucose oxidase converts glucose into gluconic acid and hydrogen peroxide, enabling urine and blood glucose measurement.
• Various enzymatic methods are used, including glucose oxidase, glucose dehydrogenase, and hexokinase.

Esterification and Oxidation Reactions

• Hydroxyl groups of sugars can form esters, typically with phosphates.
• Oxidation converts aldehydes into carboxylic acids; reduction turns aldehydes into sugar alcohols (Alditols), such as sorbitol.

Glycolysis and Gluconeogenesis

• Glycolysis breaks down glucose to produce pyruvate, ATP, and NADH in the cytoplasm without oxygen.
• Gluconeogenesis allows the production of glucose from non-carbohydrate sources to regulate blood glucose levels during deprivation.

Structural Representation of Sugars

• Sugars can be represented in straight chain form through Fisher projections or perspective structural formulas.
• Haworth projections offer a more realistic depiction of sugars compared to Fisher projections.
• In Haworth projections, substituents that are right in Fisher are down and those that are left are up.

Enantiomers

• D and L configurations indicate the spatial arrangement of glyceraldehyde.
• D-sugars possess measurable optical rotation, while L-amino acids do not.

Chirality

• Chiral centers have four distinct groups attached, leading to non-superimposable mirror images.
• Achiral molecules have superimposable mirror images.

Classification and Nomenclature

• Monosaccharides are classified as aldoses (aldehyde group) or ketoses (ketone group).
• Length classification includes trioses (3 carbons), tetroses (4), pentoses (5), and hexoses (6).

D-Glucose (Aldohexose)

• Known as grape sugar and the most abundant sugar in nature.
• Essential for human nutrition; found at high concentrations in ripe fruits (20-30% glucose).
• D-glucose is sweet and nutritious, while L-glucose is tasteless and unusable by the body.

Uses of Monosaccharides

• A 50% glucose solution is hypertonic and restores blood glucose in hypoglycemia.
• Galactose is vital for brain function, synthesized in mammary glands, and crucial for glycoprotein formation.

D-Fructose (Ketohexose)

• Also called levulose or fruit sugar, found in many fruits and the sweetest sugar.
• Used for energy in patients with hepatic disease or uncontrolled diabetes.
• Structurally similar to glucose from carbon 3 to 6.

Disaccharides

• Composed of two monosaccharide units linked by glycosidic bonds.
• Examples include sucrose (table sugar), lactose, and maltose.

Glycosidic Linkage

• Links two monosaccharides in disaccharides, formed between hydroxyl groups of the monomers.

Polysaccharides

• Composed of repeating monosaccharide units linked by glycosidic bonds.
• Identified by the type of monosaccharide, length, type of linkage, and branching degree.

Types of Polysaccharides

• Homoglycans (e.g., starch, cellulose) and heteroglycans.
• Starch consists of amylose (linear chains) and amylopectin (branched chains).
• Glycogen is a highly branched polymer of glucose for energy storage.

Starch and Cellulose

• Starch is digestible for humans, while cellulose (β-1,4 linkages) is not, creating structural importance in plants.
• Iodine stains starch blue due to helical structure of amylose.

Glycogen

• Serves as a glucose reservoir, particularly during fasting.
• Glycogenesis converts glucose to glycogen, primarily in liver and muscle for energy storage.
• Regulation involves hormones: insulin stimulates glycogenesis, while glucagon promotes glycogenolysis.

Glycogenolysis

• Process of degrading glycogen for glucose production, occurring primarily in liver and kidney cells for blood sugar maintenance.

This quiz covers the gluconeogenesis cycle, focusing on how metabolites like lactate and glycerol are processed in the liver and kidneys. It also explores the role of glucagon in regulating blood glucose levels when dietary carbohydrates are low.