Sorbitol Pathway and Osmotic Damage

An alternative method of trapping glucose in the cell is to convert it to its alcohol counterpart, sorbitol, via aldose reductase. Some tissues then convert sorbitol to fructose using sorbitol dehydrogenase; tissues with an insufficient amount/activity of this enzyme are at risk of intracellular sorbitol accumulation, causing osmotic damage (e.g., cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in diabetes).

Galactose, Sorbitol Metabolism, and LARKS

High blood levels of galactose also result in conversion to the osmotically active galactitol via aldose reductase. Liver, ovaries, and seminal vesicles have both enzymes (they lose sorbitol).

Diagram: Glucose → Sorbitol (via Aldose reductase, using NADPH) → Fructose (via Sorbitol dehydrogenase, using NAD+)

Lens has primarily Aldose reductase. Retina, Kidneys, and Schwann cells have only aldose reductase (LARKS).

Lactase Deficiency: Definition and Types

Insufficient lactase enzyme → dietary lactose intolerance. Lactase functions on the intestinal brush border to digest lactose (in milk and milk products) into glucose and galactose.

Primary: age-dependent decline after childhood (absence of lactase-persistent allele), common in people of Asian, African, or Native American descent.

Secondary: loss of intestinal brush border due to gastroenteritis (e.g., rotavirus), autoimmune disease.

Congenital lactase deficiency: rare, due to defective gene.

Lactase Deficiency: Diagnosis and Management

Stool demonstrates ↓ pH and breath shows ↑ hydrogen content with lactose hydrogen breath test (H+ is produced when colonic bacteria ferment undigested lactose). Intestinal biopsy reveals normal mucosa in patients with hereditary lactose intolerance.

Findings: Bloating, cramps, flatulence (all due to fermentation of lactose by colonic bacteria → gas), and osmotic diarrhea (undigested lactose).

Treatment: Avoid dairy products or add lactase pills to diet, lactose-free milk.

Amino Acids: Essential and Metabolic Fates

Only L-amino acids are found in proteins.

Essential: PVT TIM HALL: Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Leucine, Lysine.

Glucogenic: Methionine, histidine, valine. We met his valentine, who is so sweet (glucogenic).

Glucogenic/ketogenic: Isoleucine, phenylalanine, threonine, tryptophan.

Ketogenic: leucine, lysine. The only purely ketogenic amino acids.

Amino Acids: Acidic and Basic Properties

Acidic: Aspartic acid, glutamic acid. Negatively charged at body pH.

Basic: Arginine, histidine, lysine.

Arginine is most basic. Histidine has no charge at body pH. Arginine and histidine are required during periods of growth. Arginine and lysine are ↑ in histones which bind negatively charged DNA. His lys (lies) are basic.

Topics Covered:

• Sorbitol Pathway and Diabetic Complications
• Tissue Specificity in Polyol Pathway
• Understanding Lactase Deficiency
• Diagnosing and Treating Lactose Intolerance
• Classifying Amino Acids
• Acidic and Basic Amino Acids