Untitled Quiz

Carbohydrate Metabolism

• Dietary carbohydrates consist of polysaccharides (starch, glycogen, cellulose), disaccharides (sucrose, maltose, lactose), monosaccharides (glucose, fructose).

Digestion in Mouth

• Salivary glands secrete α-amylase.
• α-amylase acts briefly on dietary starch and glycogen, breaking some α-(1 → 4) bonds.
• α-amylase hydrolyzes starch into dextrins.

Digestion in Stomach

• Carbohydrate digestion halts temporarily in the stomach.

Digestion in Intestine

• Two phases of intestinal digestion:

  • Digestion due to pancreatic α-amylase:
    • Pancreatic α-amylase further degrades dextrins into a mixture of maltose, isomaltose, and α-limit dextrin.
    • α-limit dextrins are smaller oligosaccharides containing 3 to 5 glucose units.
  • Digestion due to intestinal enzymes:
    • Sucrose is broken down by sucrase into glucose and fructose.
    • Maltose is broken down by maltase into two glucose molecules.
    • Lactose is broken down by lactase into glucose and galactose.
    • Isomaltose is broken down by isomaltase into two glucose molecules.
    • α-limit dextrin is broken down by dextrinase into glucose and maltose.

• The end products of carbohydrate digestion are glucose, fructose, and galactose.

Absorption of Carbohydrates

• Two mechanisms are responsible for monosaccharide absorption:
  • Active transport (against concentration gradient):
    • Used for glucose and galactose transport from lower to higher concentration.
    • Requires energy and a specific transport protein.
    • Involves sodium ions.
  • Facilitative transport (with concentration gradient):
    • Used for fructose and mannose transport from higher to lower concentration.
    • Doesn't require energy, but requires a specific transporter (GLUT-5).
• Sugars are transported out of mucosal cells via GLUT-2 and into the bloodstream.

Lactose Intolerance

• Inability to digest lactose (milk sugar) due to lactase deficiency.
• Lactose undergoes bacterial fermentation, producing gases (H2, CO2, methane), and organic acids (acetic, propionic, butyric acids).
• Symptoms include abdominal cramps and flatulence, diarrhea, and dehydration.
• Treatment involves removing lactose from the diet.

Metabolic Fate of Carbohydrates

• Monosaccharides are transported to the liver via the portal circulation.
• Most glucose is phosphorylated to glucose-6-phosphate, trapped in the liver cell, and cannot diffuse back out.
• The rest of the glucose enters the bloodstream.
• Other monosaccharides (galactose and fructose) are also phosphorylated and converted into glucose.

Glycolysis

• Glycolysis (Embden-Meyerhof pathway) is the sequence of reactions that converts glucose to pyruvate in the presence of oxygen (aerobic) or lactate in the absence of oxygen (anaerobic).
• Produces ATP.
• It takes place in the cytosol of all cells.
• Two phases: energy requiring phase & energy generating phase.
• Important intermediate in glycolysis: glucose-6-phosphate & fructose-1,6-bisphosphate

Anaerobic Glycolysis

• Re-oxidation of NADH by conversion of pyruvate to lactate via lactate dehydrogenase
• Occurs in tissues functioning under hypoxic conditions: skeletal muscle, smooth muscle, and erythrocytes.

Poisons that inhibit glycolysis enzymes

• Iodoacetate: inhibits glyceraldehyde-3-phosphate dehydrogenase.
• Fluoride: inhibits enolase.
• Arsenite: interferes with the action of glycolysis enzyme phosphoglycerate kinase

Rapoport-Luebering Cycle

• Produces 2,3-BPG to regulate oxygen binding in hemoglobin.

Significance of Glycolysis

• The primary route for glucose metabolism, producing ATP.
• Also, provides a pathway for fructose and galactose metabolism.
• Enables tissues to survive anoxic episodes.

Conversion of Pyruvate to Acetyl CoA

• Pyruvate is converted to acetyl-CoA by oxidative decarboxylation.
• The reaction is irreversible and requires a multienzyme complex (pyruvate dehydrogenase).
• PDH requires five coenzymes: thiamine pyrophosphate (TPP), lipoate, coenzyme A, FAD, and NAD+.
• Produces NADH, essential for ATP production via the electron transport chain.

Citric Acid Cycle (Krebs Cycle or Tricarboxylic Acid (TCA) cycle)

• A series of reactions in mitochondria transforming acetyl-CoA to CO2 and water.
• Generates ATP by substrate-level phosphorylation and reducing equivalents that feed the electron transport chain.
• Moonlighting enzyme aconitase plays critical roles in both enzyme-mediated processes and protein synthesis regulation.

Significance of Citric Acid Cycle

• Provides energy (ATP).
• The central oxidative pathway for carbohydrates, lipids, and proteins.
• Also, provides precursors for various anabolic processes (gluconeogenesis, fatty acid synthesis, heme synthesis, and others).

Gluconeogenesis

• Synthesis of glucose from non-carbohydrate precursors.
• Major tissue for gluconeogenesis is the liver; during starvation, the kidney also participates.
• Relies on some steps from glycolysis in reverse but involves unique reactions to bypass irreversible steps in glycolysis.
• Precursors include lactate, glycerol, glucogenic amino acids, and propionic acid/intermediates of the TCA cycle.
• Cori cycle describes the relationship and interchange between the lactate produced by muscle cells to the glucose produced by the liver.

Significance of Gluconeogenesis

• Maintenance of blood glucose levels in the absence of dietary carbohydrates.
• Important during periods of fasting or starvation to ensure energy supply for essential organs (brain).
• Clears metabolic products from other tissues, such as lactate.

Regulation of Gluconeogenesis

• Four key enzymes, regulated by hormones (glucagon, insulin), and allosteric/ metabolic signals
• Pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, glucose-6-phosphatase. - Glucagon & epinephrine stimulate gluconeogenesis, insulin inhibits

Glycogen Metabolism

• Includes glycogenesis (formation of glycogen) and glycogenolysis (degradation of glycogen).
• Both processes occur in the cytosol, primarily in liver and muscle.

Glycogenesis

• Pathway forming glycogen from glucose.
• Requires energy (ATP and UTP).
• Key enzyme: glycogen synthase

Glycogenolysis

• Degradation of glycogen to glucose-6-phosphate in muscle and glucose in liver,
• Involves glycogen phosphorylase and debranching enzymes.
• Important for rapid blood glucose provision between meals.

Significance of Glycogenolysis and Glycogenesis

• Maintaining blood glucose levels.
• Storing excess glucose as glycogen.

Regulation of Glycogenesis and Glycogenolysis

• Glycogen phosphorylase and glycogen synthase are reciprocally regulated by allosteric and hormonal mechanisms.

Allosteric Regulation of Glycogenesis and Glycogenolysis

• The enzymes involved have opposing allosteric responses.
• ATP inhibits glycogen breakdown, AMP stimulates glycolysis
• Glucose-6-phosphate inhibits glycogen breakdown, glucose-1-phosphate stimulates glycogen synthesis.

Hormonal regulation of glycogen metabolism

• Glucagon and epinephrine stimulate glycogenolysis and glycogen phosphorylase; insulin inhibits gluconeogenesis by repressing the synthesis of key enzymes

Glycogen Storage Disease

• Group of inherited disorders from defects in glycogen synthesis or breakdown.
• Characterized by abnormal glycogen accumulation in specific tissues.
• Symptoms vary based on affected enzyme & tissue

Pentose Phosphate Pathway

• Alternative pathway for glucose oxidation, producing NADPH and pentose phosphates.
• Important for reducing equivalents for biosynthetic processes and antioxidant defense.
• The enzymes are located in the cytosol of all cells and tissues most enriched in the enzymes include tissues requiring high amounts of NADPH (adrenal gland, testes, ovaries, liver, red blood cells etc)

Significance of Pentose Phosphate Pathway

• Synthesis of nucleotides, coenzymes, and other important molecules.
• Produces NADPH (a reducing agent needed for reductive biosynthetic reactions (including the synthesis of fatty acids, sterols, and some amino acids.
• Protects against oxidative damage by neutralizing reactive oxygen species.

Regulation of Pentose Phosphate Pathway

• Glucose-6-phosphate dehydrogenase is the rate-limiting enzyme.
• Its activity is regulated by the concentration of its product, NADPH (competitive inhibition).

Uronic Acid Pathway (Glucuronic Acid Cycle)

• Pathway in the liver for converting glucose into glucuronic acid and ascorbic acid (except in humans).
• Pathway is a source for UDP glucuronate.
• Involved in protein and glycoprotein synthesis and many detoxification processes

Galactose Metabolism and Galactosemia

• Galactose is derived from the disaccharide lactose.
• Galactose is readily converted to glucose in the liver and it is incorporated into glycoproteins.
• Galactosemia is caused by a deficiency in the enzyme galactose-1-phosphate uridyl transferase.
• Symptoms include elevated galactose blood and urine levels, accumulation of galactose-1-P, galactitol, and lens cataracts.
• Treatment involves removing galactose from the diet.

Fructose Metabolism

• Fructose is channelled into the glycolytic pathway.
• Two pathways for fructose metabolism are the liver fructose-1-phosphate pathway & sorbitol pathway.
• Essential fructosuria results from a deficiency in fructokinase. Symptoms include fructose excretion in urine.
• Hereditary fructose intolerance results from a deficiency in the enzyme aldolase B. Symptoms include fructose-1-phosphate buildup, liver and kidney damage and hypoglycemia.

Blood Glucose Level and Its Regulation

• Blood glucose levels are maintained within a normal range (70-100 mg/dL) through a complex interplay of hormones and metabolic processes.
• Hormones: Insulin (hypoglycemic) and glucagon (hyperglycemic).
• Liver is the primary organ controlling blood glucose.
• Renal mechanism plays a role to control high blood glucose with glycosuria.

Diabetes Mellitus

• A syndrome of impaired carbohydrate, fat, and protein metabolism.
• Caused by either lack of insulin secretion or impaired insulin action
• Two major types are Type I and Type II.

Type I Diabetes Mellitus

• Characterized by the deficiency of insulin production due to the destruction of the beta cells in the pancreas.
• Usually begins in childhood/adolescence – acute onset
• Symptoms include polyuria, polyphagia, polydipsia, ketoacidosis, and weight loss
• Treatment: requires exogenous insulin administration

Type II Diabetes Mellitus

• Characterized by insufficient insulin action in tissues that causes increased resistance and deficiency to insulin, resulting in increased blood sugar levels.
• Usually develops in adulthood – gradual onset
• Symptoms are gradually developed and usually not accompanied by ketonuria or acidosis
• Treatment: diet, exercise, weight reduction, possible use of insulin-sensitizing drugs in advanced stages

Gestational Diabetes Mellitus (GDM)

• High blood sugar levels during pregnancy that resolve after delivery.
• Women with GDM are at greater risk for developing type II diabetes later in life or pre-eclampsia.

Glucose Tolerance Test (GTT)

• A test that measures how well the body handles glucose.
• Used to diagnose diabetes and some related conditions.

Disorders of Glucose Homeostasis

• Diseases resulting in disturbances of glucose homeostasis are known as metabolic disorders, some of which include inborn errors and/or genetic disorders