SPEX

Twenty standard amino acids form proteins. Essential amino acids (must be obtained from diet): phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, leucine, lysine, histidine. Nonessential amino acids are synthesized endogenously.

Protein structure levels: primary (amino acid sequence), secondary (alpha-helices, beta-sheets), tertiary (3D folding), quaternary (multiple polypeptide subunits). Denaturation disrupts secondary/tertiary/quaternary structure but not primary sequence.

Post-translational modifications include phosphorylation (adds phosphate groups, regulates enzyme activity), glycosylation (adds carbohydrate chains), ubiquitination (marks proteins for degradation).

Enzymes lower activation energy without altering equilibrium. Michaelis-Menten kinetics: Vmax is maximum reaction velocity; Km is substrate concentration at half-Vmax (reflects enzyme-substrate affinity — lower Km means higher affinity).

Enzyme inhibition types:

Glycolysis occurs in cytoplasm, converts glucose to 2 pyruvate molecules, yields 2 ATP and 2 NADH (net). Key regulatory enzymes: hexokinase/glucokinase, phosphofructokinase-1 (PFK-1, rate-limiting), pyruvate kinase.

Gluconeogenesis synthesizes glucose from non-carbohydrate precursors (lactate, amino acids, glycerol). Occurs primarily in liver and kidney. Bypass enzymes: pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase, glucose-6-phosphatase.

Glycogenesis: glucose storage as glycogen (liver, muscle). Glycogenolysis: glycogen breakdown. Glycogen storage diseases result from enzyme deficiencies (Von Gierke disease: glucose-6-phosphatase deficiency; Pompe disease: acid maltase deficiency; McArdle disease: muscle glycogen phosphorylase deficiency).

Pentose phosphate pathway generates NADPH (for fatty acid synthesis, glutathione reduction) and ribose-5-phosphate (for nucleotide synthesis). G6PD deficiency causes hemolytic anemia with oxidative stress.

Citric acid cycle (Krebs cycle) occurs in mitochondrial matrix. Acetyl-CoA enters cycle, produces 3 NADH, 1 FADH2, 1 GTP per turn. Key enzymes: citrate synthase, isocitrate dehydrogenase (rate-limiting), alpha-ketoglutarate dehydrogenase.

Electron transport chain located in inner mitochondrial membrane. NADH yields approximately 2.5 ATP; FADH2 yields approximately 1.5 ATP. Total ATP from complete glucose oxidation: approximately 30-32 ATP.

Fatty acid synthesis occurs in cytoplasm, requires acetyl-CoA, NADPH, and ATP. Rate-limiting enzyme: acetyl-CoA carboxylase.

Beta-oxidation breaks down fatty acids in mitochondria, producing acetyl-CoA, NADH, and FADH2. Carnitine shuttle transports long-chain fatty acids into mitochondria.

Ketogenesis produces ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) in liver during fasting, starvation, or uncontrolled diabetes. Ketone bodies serve as alternative fuel for brain and heart.

Cholesterol synthesis: rate-limiting enzyme is HMG-CoA reductase (target of statins).

Purines (adenine, guanine): synthesized de novo or via salvage pathway. Degradation produces uric acid. Gout results from uric acid accumulation. Lesch-Nyhan syndrome: HGPRT deficiency causing hyperuricemia, intellectual disability, self-mutilation.

Pyrimidines (cytosine, thymine, uracil): degraded to water-soluble products (no uric acid).