Biochemistry Complete

Alcohol dehydrogenase

Enzyme that converts ethanol to acetaldehyde, work in the cytosol. Inhibited by fomepizole.

Acetaldehyde dehydrogenase

Enzyme that converts acetaldehyde to acetate, work in the mitochondria. Inhibited by disulfiram.

Catalase

Enzyme that breaks down hydrogen peroxide into water and oxygen.

Fomepizole

Competitive inhibitor of alcohol dehydrogenase, by inhibiting the first step in alcohol metabolism decreases the conversion rate of the parent alcohols into their toxic metabolites. Used as an antidote for methanol or ethylene glycol acute poisoning.

Disulfiram

Blocks acetaldehyde dehydrogenase, leading to unpleasant symptoms when alcohol is consumed (increase hangover). Used to treat alcohol dependence.

Peroxisome

Membrane-enclosed Organelle involved in several anabolic and catabolic processes. Functions include β-oxidation of very long chain fatty acids, α-oxidation, and synthesis of cholesterol, bile acids and plasmalogens, catabolism of amino acids and ethanol.

Mitochondria

Cellular organelles responsible for energy production through oxidative phosphorylation.

Cytosol

Fluid portion of the cytoplasm, where many metabolic reactions occur.

Microsome

Small vesicles derived from the endoplasmic reticulum, involved in drug metabolism.

Nicotinamide adenine dinucleotide (NADH)

Coenzyme involved in redox reactions.

Nicotinamide adenine dinucleotide phosphate (NADPH)

Coenzyme involved in anabolic reactions.

Nicotinamide adenine dinucleotide phosphate (NADP+)

Oxidized form of NADPH.

Acetate

End product of ethanol metabolism, which can be further metabolized or used for energy production.

Lipogenesis

Synthesis of fatty acids and triglycerides.

Ketogenesis

Production of ketone bodies from acetyl-CoA.

Glyceraldehyde-3-P

Intermediate in glycolysis and gluconeogenesis.

Pyruvate

End product of glycolysis, which can be further metabolized or used for energy production.

Lactate

Byproduct of anaerobic metabolism, often associated with lactic acidosis.

Fatty acids

Molecules used for energy storage and as building blocks for lipids.

Ketoacids

Organic acids produced during ketogenesis.

Glycerol-3-P

Intermediate in glycolysis and lipogenesis.

Nicotinamide adenine dinucleotide (NAD+)

Oxidized form of NADH.

CYP2E1

Cytochrome P450 enzyme involved in the metabolism of ethanol and other substances.

NADH/NAD+ ratio

Ratio of reduced to oxidized forms of NADH and NAD+.

Acetyl-CoA

Molecule involved in the metabolism of carbohydrates, fats, and proteins.

Malate

Intermediate in the TCA cycle.

Succinyl-CoA

Intermediate in the TCA cycle.

Oxaloacetate (OAA)

Intermediate in the TCA cycle and gluconeogenesis.

Isocitrate dehydrogenase

Intermediate in the TCA cycle. Regulators: ADP (+), ATP (-), NADH (-).

Alpha-ketoglutarate (α-KG)

Intermediate in the TCA cycle.

Dihydroxyacetone phosphate (DHAP)

Intermediate in glycolysis and lipogenesis.

Adenosine monophosphate (AMP)

Nucleotide involved in energy metabolism.

Adenosine triphosphate (ATP)

Main energy currency of cells.

Citrate

Intermediate in the TCA cycle and fatty acid synthesis.

HMP shunt

Metabolic pathway involved in the production of NADPH and ribose-5-phosphate.

Glucose-6-phosphate dehydrogenase (G6PD)

Rate-limiting enzyme in the pentose phosphate pathway, the major source of cellular NADPH.  This molecule is necessary for reducing glutathione (protects red blood cells from oxidative damage) and for the biosynthesis of cholesterol, fatty acids, and steroids

Carbamoyl phosphate synthetase II

Enzyme involved in de novo pyrimidine synthesis. Regulators: ATP (+), PRPP (+), UTP (-).

Uracil triphosphate (UTP)

Nucleotide involved in RNA synthesis.

Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase

Enzyme involved in de novo purine synthesis. Regulators: AMP (-), IMP (-), GMP (-).

Inosine monophosphate (IMP)

Nucleotide involved in purine metabolism.

Guanosine monophosphate (GMP)

Nucleotide involved in purine metabolism.

Carnitine acyltransferase I

Enzyme involved in fatty acid oxidation. Regulators: Malonyl-CoA (-).

HMG-CoA synthase

Enzyme involved in ketogenesis.

HMG-CoA reductase

Enzyme involved in cholesterol synthesis. Regulators: Insuline (+), thyroxine (+), estrogen (+), glucagon (-), cholesterol (-).

Glycolysis

Metabolic pathway that converts glucose into pyruvate, producing ATP and NADH in the process.

Gluconeogenesis

Synthesis of glucose from non-carbohydrate sources, such as amino acids and glycerol.

TCA cycle

Series of chemical reactions that generate energy through the oxidation of acetyl-CoA.

Acetyl-CoA Carboxylase (ACC)

Enzyme involved in fatty acid synthesis. Regulators: Insuline (+), citrate (+), glucagon (-), palmitoyl-CoA (-).

Hexokinase

Enzyme that phosphorylates glucose to produce glucose-6-phosphate in most tissues, except liver and pancreatic beta cells. No induced by insulin. Sequesters glucose in tissues where it is used when glucose concentration are low

Glucokinase

Enzyme that phosphorylates glucose in the liver and pancreatic beta cells to produce glucose-6-phosphate. Induced by insuline. At high glucose concentrations, helps to stored in liver.

Flavin adenine dinucleotide (FADH2)

Coenzyme involved in redox reactions and energy production.

Coenzyme A (CoA)

Molecule involved in various metabolic pathways, including fatty acid oxidation and the TCA cycle.

Biotin

Vitamin that serves as a cofactor for carboxylation reactions.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)

Intermediate in the synthesis of cholesterol and ketone bodies.

Thiamine

Vitamin that serves as a cofactor for several enzymes involved in carbohydrate metabolism.

Arsenic

Toxic element that binds to sulfhydryl groups, impairing cellular respiration via inhibition of pyruvate deshydrogenase and disruption of gluconeogenesis and glutathione metabolism. Common sources includes pesticides/insecticides, contaminated water (often from wells), and ressure-treated wood.

ATP hydrolysis

Breakdown of ATP into ADP and inorganic phosphate, releasing energy.

Activated carriers

Molecules that carry high-energy groups or electrons for use in metabolic reactions.

Nicotinamides

NAD+ and NADP+, coenzymes involved in redox reactions.

Km

Michaelis constant, a measure of the affinity of an enzyme for its substrate.

Vmax

Maximum velocity or rate of an enzyme-catalyzed reaction.

Phosphofructokinase-1

Rate-limiting enzyme in glycolysis that converts fructose-6-phosphate to fructose-1,6-bisphosphate.

Pyruvate kinase

Enzyme that converts phosphoenolpyruvate to pyruvate, producing ATP.

Fructose bisphosphatase-2 (FBPase-2)

Enzyme involved in the regulation of gluconeogenesis and glycolysis.

Phosphoenolpyruvate

Intermediate in glycolysis that is converted to pyruvate.

Pyruvate dehydrogenase complex

Mitochondrial enzyme complex that links glycolysis and the TCA cycle.

Pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase complex cofactors

Thiamine pyrophosphate (B1), FAD (B2, riboflavin), NAD+ (B3, niacin), CoA (B5, pantothenic acid), lipoic acid.

Pyruvate dehydrogenase complex deficiency

X-linked disorder that causes buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT). Findings: neurologic defects, lactic acidosis, increase serum alanine starting in infancy. Treatment: Increase intake of ketogenic nutrients (eg, high fat content or high lysine and leucine).

Alanine aminotransferase (ALT)

Enzyme that transfers amino groups to the liver from muscle. Cofactor: B6.

Pyruvate carboxylase

Enzyme that converts pyruvate to oxaloacetate. Cofactor: B7.

Lactic acid dehydrogenase

Enzyme that converts pyruvate to lactate in anaerobic conditions. Major pathway in RBCs, WBCs, kidney medulla, lens, testes, and cornea. Cofactor: B3.

Citrate synthase

Enzyme that catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate in the TCA cycle.

Isocitrate dehydrogenase

Enzyme that converts isocitrate to alpha-ketoglutarate in the TCA cycle.

Alpha-ketoglutarate dehydrogenase complex

Mitochondrial enzyme complex that converts alpha-ketoglutarate to succinyl-CoA in the TCA cycle.

Electron transport chain

Series of protein complexes in the inner mitochondrial membrane that transfer electrons and generate a proton gradient, which is used to produce ATP through oxidative phosphorylation.

Mitochondrial matrix

Innermost compartment of the mitochondria where the citric acid cycle (TCA cycle) takes place.

Inner mitochondrial membrane

Membrane that separates the mitochondrial matrix from the intermembrane space and contains the protein complexes of the electron transport chain.

Intermembrane space

Space between the inner and outer mitochondrial membranes.

Complex I of electron transport chain

Transfer of electrons from NADH to coenzyme Q, with the transfer generating a proton gradient which accepts electrons from NADH.

Complex II of electron transport chain

Also know as succinate dehydrogenase, generates FADH2 via the oxidation of succinate to fumarate. The electrons from FADH2 then enter the ETC to generate ATP via oxidative phosphorylation.

Complex III of electron transport chain

Transfer of electrons from ubiquinol to cytochrome c, with the transfer generating a proton gradient.

Complex IV of electron transport chain

Transfers electrons to oxygen to form water.

Complex V of electron transport chain

Also known as ATP synthase, the coupling of proton gradient to ATP synthesis. The flow of protons down their electrochemical gradient into the mitochondrial matrix provides the energy required for production of ATP via oxidative phosphorylation.

Oligomycin

Inhibitor of ATP synthase, which blocks ATP production.

2,4-Dinitrophenol

Uncoupling agent that increases the permeability of the mitochondrial membrane, disrupting the proton gradient and causing heat production.

Phosphoenolpyruvate carboxykinase

Enzyme involved in gluconeogenesis that converts oxaloacetate to phosphoenolpyruvate in the cytosol.

Fructose-1,6-bisphosphatase

Enzyme involved in gluconeogenesis that converts fructose-1,6-bisphosphate to fructose-6-phosphate in the cytosol.

Glucose-6-phosphatase

Enzyme involved in gluconeogenesis that converts glucose-6-phosphate to glucose in the ER. Muscle does not have it.

Nicotinamide adenine dinucleotide phosphate (NADPH)

Coenzyme involved in reductive reactions, such as fatty acid and cholesterol biosynthesis.

Glucose-6-phosphate dehydrogenase deficiency

X linked recessive disorder. Most common human enzyme deficiency more prevelent among descendants of populations in malaria endemic regions. Causes decreased NADPH production and increased susceptibility to oxidative damage in red blood cells. Findings: hemolytic anemia, heinz bodies, bite cells. Precipitate by oxidizing agents (eg, fava beans, sulfonamides, nitrofurantoin, primaquine), and infections.

Heinz bodies

Denatured globin chains that precipitate within red blood cells due to oxidative stress.

Bite cells

Red blood cells that have undergone phagocytic removal of Heinz bodies by splenic macrophages.

Essential fructosuria

Caused by fructokinase deficiency. Benign, asymptomatic condition, fructose appears in the blood and urine. Copper reduction test positive (reducing sugar in urine). Hexokinase becomes primary pathway for converting fructose to fructose-6-phosphate. No treatment.

Hereditary fructose intolerance

Caused by deficiency of aldolase B, causing fructose-1-phosphate accumulation that leads to inhibition of glycogenolysis and gluconeogenesis. Presents with hypoglycemia, jaundice, hepatomegaly, cirrhosis, vomiting, failure to thrive only following consumptions of fruit, juice or honey. Reducing sugar can be detected in the urine. Treatment: Reduce intake of fructose, sucrose, and sorbitol.

Classic galactosemia

Caused by galactose-1-phosphate uridyltransferase, GALT deficiency. Symptoms start when infant is fed formula or breast milk. Manifests with failure to thrive, jaundice, vomiting, hepatomegaly, E. coli sepsis, infantile cataracts (galatiol deposition), intellectual disability, renal dysfunction, as well as a loss of muscle tone. Treatment: Exclude galactose and lactose from diet.

Sorbitol

Alcohol counterpart of glucose, formed via aldose reductase (also convertes galactose to galactitol). Some tissues then convert it to fructose using sorbitol dehydrogenase. Tissues with an insufficient amount/activity of this enzyme are at risk of intracellular accumulation causing osmotic damage (cataracts, retinopathy, and peripheral neuropathy).

Lactase deficiency

Insufficient lactase enzyme leading to lactose intolerance. Findings: bloating, cramps, flatulence, osmotic diarrhea, stool with low pH and breath shows increase hydrogen content. Congenital/hereditary due to defective gene, intestinal biopsy revels normal mucosa. Primary: age-dependent deckine after childhood. Secondary: loss of intestinal brush border due to gastroenteritis, autoimmune disease.

Essential amino acids

Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Leucine, Lysine. (PVT TIM HaLL)

Acidic amino acids

Aspartic acid and glutamic acid, negatively charged at body pH.

Basic amino acids

Arginine, histidine, and lysine, with arginine being the most basic and histidine having no charge at body pH.