Biochemistry Lectures 17–21: Nitrogen Metabolism, Liver & Excretory Systems, Muscle & Brain Metabolism

Vocabulary-style flashcards covering nitrogen metabolism, urea cycle, liver/kidney/pancreas functions, detox, and muscle/brain metabolism.

Nitrogen balance

Difference between nitrogen intake and nitrogen loss; neutral in healthy adults, positive with growth/pregnancy, negative with starvation/injury.

Central amino acid pool

Concept that amino acids are not stored individually but cycle in a common pool used for protein synthesis and energy.

Ubiquitin–proteasome system

ATP-dependent protein degradation pathway in the cytoplasm.

Lysosome proteolysis

ATP-independent degradation of proteins in lysosomes.

Zymogen

Inactive enzyme precursor activated in digestion (e.g., pepsinogen to pepsin).

Celiac disease

Gluten (glutelin + prolamin)–induced damage to the small intestine.

Malabsorption syndromes

Protein intolerance/allergies and related pathologies (e.g., Crohn’s, cystic fibrosis) with protein in feces.

Essential amino acids

AAs that must be obtained from diet because they cannot be synthesized de novo.

Transamination

Transfer of an amino group from an amino acid to a keto acid via aminotransferases.

Glutamate dehydrogenase (oxidative deamination)

Enzyme that converts glutamate to α-ketoglutarate with release of ammonia.

ALT and AST

Aminotransferases; ALT is alanine aminotransferase, AST is aspartate aminotransferase; elevations indicate liver injury.

Urea cycle

Liver pathway converting ammonia and aspartate to urea for renal excretion; key enzymes include CPS1 and OTC.

CPS1 (carbamoyl phosphate synthetase I)

Rate-limiting urea cycle enzyme activated by N-acetylglutamate; location: mitochondria.

OTC (ornithine transcarbamylase)

Urea cycle enzyme; deficiency causes common urea cycle disorders.

Hyperammonemia

Elevated ammonia; can cause CNS toxicity; treated with protein restriction, dialysis, arginine, and ammonia scavengers.

Glucogenic amino acids

AAs broken down into glucose precursors (pyruvate or TCA intermediates).

Ketogenic amino acids

AAs that yield acetyl-CoA or acetoacetate for ketone body production; leucine and lysine are strictly ketogenic.

Phenylketonuria (PKU)

Defect in phenylalanine hydroxylase; neurotoxicity; managed by diet and providing tyrosine.

Maple syrup urine disease (MSUD)

Defect in branched-chain amino acid catabolism; neurological symptoms and distinctive urine odor.

Alkaptonuria

Defect in tyrosine metabolism; accumulation of homogentisic acid; dark urine and arthritis.

SCID (severe combined immunodeficiency)

ADA deficiency leading to dATP accumulation; treated with bone marrow/gene therapy and protective environments.

Gout

Hyperuricemia with uric acid deposition; influenced by diet, lifestyle, genes; treated with low-purine diet and allopurinol.

Heme/porins synthesis

Heme formed with four nitrogens from glycine; most heme made in bone marrow; some in liver.

Creatine

Produced in liver/kidney; travels to muscle/brain; creatine phosphate acts as rapid energy reserve.

Melanin

Pigment produced by melanocytes in the epidermis; eumelanin vs pheomelanin protect against UV.

Catecholamines

Tyrosine-derived hormones/neurotransmitters (epinephrine, norepinephrine, dopamine) important for fight/flight; DOPA used in Parkinson’s therapy.

Nitric oxide (NO)

Endothelium-derived vasodilator; supports smooth muscle relaxation; inhibited by PDE5 inhibitors like sildenafil.

S-adenosylmethionine (SAM)

Methyl donor cofactor; investigated as an anti-cancer agent.

Liver

Largest metabolic organ; detox; bile production; central hub for metabolism and storage.

Hepatocytes

Main liver cells; oxygen gradient from periportal to perivenous regions affects metabolism.

Kupffer cells

Liver macrophages that clear bacteria and debris from blood.

Stellate cells

Store vitamin A and contribute to liver fibrosis when activated.

Bile

Digestive fluid produced by the liver and stored in the gallbladder; released into the small intestine.

Phase 1 detoxification (CYP450)

Oxidation/hydroxylation in smooth endoplasmic reticulum; uses NADPH; can activate or inactivate drugs; induction increases clearance.

Phase 2 detoxification (conjugation)

Conjugation reactions adding sulfate, glucuronic acid, acetyl groups, or amino acids to increase solubility.

N-acetylcysteine

Antidote for acetaminophen toxicity; replenishes glutathione.

Phase 3 elimination

Excretion of modified compounds via urine or bile based on size/polarity.

Fed state vs starved state

Fed state: high insulin, anabolic metabolism; starved state: low insulin, high glucagon/epinephrine, gluconeogenesis and lipolysis dominate.

Amino acids for liver detox pathways

Cysteine, methionine, and glycine are particularly important for detoxification processes.

Gluconeogenesis

Production of glucose from non-carbohydrate substrates (e.g., amino acids) during fasting.

Blood urea nitrogen (BUN)

Blood measurement of urea; marker of kidney function.

Glomerular filtration rate (GFR)

Rate at which the kidneys’ glomeruli filter plasma; key measure of kidney function.

Glucose reabsorption threshold

Filtered glucose reabsorption capacity: typically around 180–220 mg/dL; exceeding threshold leads to glucose in urine.

Azotemia

Elevated nitrogenous waste (creatinine, urea) in blood; can be asymptomatic or indicate kidney dysfunction.

Anuria/Oliguria/Polyuria

Anuria: no urine; oliguria: very little urine; polyuria: excessive urine output.

Renin–angiotensin–aldosterone system (RAAS)

Hormonal system regulating BP and fluid balance; renin cleaves angiotensinogen to ANG I, leading to ANG II and aldosterone effects.

Erythropoietin

Kidney-derived hormone that stimulates red blood cell production in response to hypoxia.

Pancreas endocrine function

Islets of Langerhans secrete insulin (beta cells) and glucagon (alpha cells).

Pancreas exocrine function

Acinar cells secrete digestive enzymes (amylase, lipase, proteases, nucleases) and bicarbonate as zymogens.

Pancreatitis

Inflammation due to premature enzyme activation; symptoms include abdominal pain; elevated amylase/lipase; treat with fluids and supportive care.

Skeletal muscle metabolism basics

Muscle is a major fuel consumer; can supply substrates for gluconeogenesis during fasting.

GLUT4

Insulin-responsive glucose transporter in muscle and adipose tissue.

LPL (lipoprotein lipase)

Enzyme that hydrolyzes triglycerides in lipoproteins for fatty acid uptake.

Ketone bodies

Acetoacetate and beta-hydroxybutyrate produced during fasting; used by brain and muscle when glucose is limited.

Brain metabolism (starvation adaptation)

Brain primarily uses glucose but shifts to ketone bodies during prolonged fasting to spare protein.

Stroke types

Ischemic stroke: obstruction of blood flow; hemorrhagic stroke: vessel rupture.

Blood–brain barrier (BBB)

Endothelial barrier with astrocytes and pericytes; regulates transport of glucose and amino acids to the brain.