Major Concepts in Cellular Signaling and Tissue Anatomy

Major course themes

Metabolism, cell biology, disease pathogenesis, organ systems.

Principles of metabolism

Enzymes + cofactors; compartmentalized; organ-specific; regulated.

Rate-limiting step

Irreversible step controlling pathway flux.

Allosteric regulation

Feedback inhibition or activation of enzymes.

Covalent modification

Phosphorylation/dephosphorylation controlling enzyme activity.

Genetic regulation of metabolism

Long-term control via transcriptional changes.

Metabolic pathways location: mitochondria

TCA cycle, oxidative phosphorylation, FA oxidation, AA breakdown.

Metabolic pathways location: cytosol

Glycolysis, PPP, FA synthesis, gluconeogenesis (partial).

Metabolic pathways location: lysosome

Acidic degradation of macromolecules.

Metabolic pathways location: rough ER

Protein synthesis and folding.

Metabolic pathways location: smooth ER

Lipid and steroid synthesis.

Metabolic pathways location: Golgi

Protein processing and sorting.

Urea cycle purpose

Convert toxic ammonia → urea.

Key urea cycle enzymes

CPS1, OTC, ASS, ASL, arginase.

Hyperammonemia

Caused by urea cycle defects.

Enzymes require cofactors

Vitamins and minerals essential for catalysis.

Water-soluble vitamins

Converted into coenzymes for metabolic reactions.

Vitamin B6 (pyridoxine)

Forms PLP; used for amino group transfer.

Vitamin B1 (thiamine)

Forms TPP; used for aldehyde transfer.

Vitamin B2 (riboflavin)

Forms FAD/FMN; redox reactions.

Vitamin B3 (niacin)

Forms NAD+/NADP+; redox reactions.

Biotin

Used for carboxylation reactions.

Pantothenic acid

Forms CoA; acyl transfer.

Folic acid

Forms THF; one-carbon transfers.

Ascorbic acid (vitamin C)

Used for hydroxylation reactions.

Thermodynamics of metabolic pathways

Near-equilibrium vs far-from-equilibrium reactions.

Metabolic flux

Determined by rate-limiting step.

Protein folding location

Occurs in ER and cytosol with chaperones.

Unfolded protein response (UPR)

Triggered by misfolded proteins; increases chaperones; decreases translation.

Diseases caused by ER misfolding

CFTR defects, α1-antitrypsin deficiency, LDL receptor mutations.

Proteasome function

Degrades ubiquitinated proteins.

Ubiquitin

Tag marking proteins for proteasomal degradation.

Proteasome inhibitor example

Bortezomib; used for multiple myeloma.

Lysosome function

Acidic degradation of endocytosed material.

Lysosomal storage disorders

Caused by defective lysosomal enzymes.

Cellular signaling importance

Controls metabolism, growth, immunity, tissue function.

Gene expression control levels

Transcription, processing, transport, translation, degradation.

Epigenetics

Promoters and enhancers regulate gene expression.

Metabolic coordination across organs

Liver, muscle, adipose, intestine share metabolic responsibilities.

Nutrition as disease modifier

Diet influences cancer, diabetes, heart disease.

Calorie restriction effect

Increases lifespan in mice.

Ketogenic diet

High fat, low carb; reduces pediatric seizures.

Native American succotash example

Beans + corn complement amino acid deficiencies.

Why study disease pathogenesis

Understanding molecular basis enables therapy development.