FOM Comp I: Biochemistry, Microbiology, Clinical Correlations, and Embryology

(6) Hyaline Cartilage

Type of cartilage found in long bones, epiphyseal plates, and articular surfaces of synovial joints

(11) Sickle Cell Anemia

G6V Substitution, leads to hydrophobic patch on Hb. Unstable hemoglobin leads to red cell breakdown, anemia, capillary occlusion, and pain in the extremities

(11) Protein Conformational Disorders

Proteins have altered confirmations resulting in cellular toxicity, functional deficiency, or dominant negative effects. Eg Alzheimer’s Disease, Parkinson’s, BSE

(11) Marasmus

Deficient in protein and calories; no edema

(11) Kwashiorkor

Protein deficient but enough calories

(11) Phenylketonuria (PKU)

Cannot process Phenylalanine; Tyrosine replaces it as an essential Amino Acid

(23) Effects of Starvation

Spike in Gluconeogenesis, Increase in ketone bodies in blood, TCA cycle intermediates cannot be made

(18) Hb Hammersmith

F42S, breaks the hydrophobic barrier around the heme and allows water access to the pocket, leading to heme loss

(18) Hb Savannah

G24V, leads to unstable Hemoglobin

(18) Hb Milwaukee

V67E, stabilizes Methemoglobin (causes blue skin and anemia)

(18) HbC disease

E6K leading to mild anemia

(19) Scurvy

Low Vitamin C leads to low hydroxylation of proline and lysine. Poor assembly and crosslinking of collagen, leading to weak blood vessels and poor wound healing

(19) Ehlers Danlos Syndrome (EDS)

Type 3 Collagen affected (either by mutations in genes or defective collagen processing enzymes) leading to weak bones and muscle, hyperextensible skin, hypermobile joints and skin, and easy bruising

(19) Menkes Disease

Impaired Copper absorption. Less copper leads to lower lysyl oxidase activity (collagen processing enzyme) leading to poor collagen crosslinking. Floppy muscle, kinky hair, intellectual disability.

(19) Osteolathyrism

Caused by toxic osteolathrogens that inhibit lysyl oxidase (collagen processing enzyme), soft deformed bones and weak muscles

(19) Collagen Vascular Diseases

Autoimmune diseases, the body’s collagen is not recognized as native leading to immune response. Eg Ankylosing spondylitis, Dermatomyositis, Polyarteritis nodosa, Psoriatic arthritis, Rheumatoid arthritis, Scleroderma, Vasculitis

(19) Osteogenesis Imperfecta

Mutation in Type 1 Collagen gene, causing inability of triple helix and imperfect formation of bones (aka brittle bone disease), leading to a group of genetic disorders where bones easily bend and fracture

(19) Marfan Syndrome

Mutations in the FBN1 gene, which encodes Fibrillin-1. Clinical manifestations include elongated limbs, flexible joints, scoliosis, aortic aneurysm

(19) Emphysema

AAT counteracts Elastase and preserve Elastin. In AAT deficient patients elastase is unopposed, causing destruction of the connective tissues of alveolar walls
-smoking could prevent binding between AAT and Elastase

(20) Function of Kinases

Adds Phosphate to Enzyme

(20) Function of Phosphatase

uses H₂O to remove phosphoryl group

(20) Function of Phosphorylase

Use inorganic phosphate (Pi) to break a bond and generate a phosphorylated product; Adding the phosphate to an enzyme INACTIVATES the enzyme

(20) Inorganic cofactors of enzymes

often metal ions, such as copper, zinc, iron (in the heme molecule); may function as Structural elements, Redox centers

(20) Function of Oxidoreductases

catalyze the redox reactions

(20) Function of Transferases

transfer functional groups from a donor to an acceptor

(20) Function of Hydrolases

catalyze the cleavage of bonds by addition of a water molecule (hydrolysis)

(20) Function of Lyases

cleave C-C, or C-S, or C-N bonds

(20) Function of Isomerases

catalyze the racemization of optical or geometric isomers (isomerization)

(20) Function of Ligases

catalyze the bond formation with concomitant expenditure of energy in the form of ATP

(20) velocity (V)

number of substrate molecules converted to products per unit time, usually expressed as μM/min

(20) V_max

Maximum rate of an enzyme-catalyzed reaction; will not increase even with more substrate concentration. measure of how fast the enzyme can convert the substrate to the product when the reaction is not limited by the availability of the substrate

(20) Factors affecting reaction velocity

Temperature, pH (usually 7.4 is optimal)

(20) Michaelis-Menten Kinetic Model

V₀ = (V_max [S]) / (K_m + [S]) , where V₀ - initial velocity, K_m is the Michaelis constant, [S] is substrate concentration

(20) Irreversible Inhibition

Causes the inactivation of an enzyme usually by reacting covalently with the enzyme

(20) Reversible Inhibition

Noncovalent interaction between the enzyme and the inhibitor; Inhibition can be reversed upon removal of the inhibitor

(20) Competitive Inhibition

Reversible Inhibition in which the inhibitor binds to the same site as the substrate

(20) Noncompetitive Inhibition

Reversible Inhibition in which the inhibitor binds to a different site as the substrate

(20) Allosteric regulation of enzyme activity

allosteric enzyme possess site in which an effector can bind noncovalently and reversibly, changing activity of enzyme positively or negatively

(20) Feedback Inhibition

the downstream product of an enzymatic reaction is a negative effector of the upstream enzyme, slowing down production of product

(20) Hormonal control of enzyme activity

organic molecules or small peptides released by a source, which then travel in the blood to the target tissues/organs and regulate the metabolic state of the target tissues/organs by activating or inactivating certain enzymes

(20) Nuclear receptors

specific protein receptors in the nucleus that Nonpolar hormones such as steroid hormones can enter the nucleus and bind to; can stimulate (or inhibit) the production of certain mRNAs, resulting in the increase (or decrease) of an enzyme

(21) Biological Markers of Muscle Damage

Aldolase from Gluconeogenesis is high, AST and ALT, Creatine Kinase

(21) Biological Markers of Liver Damage

AST and ALT

(21) Biological Markers of Heart Attack

Cardiac Troponin, CK-MB

(22) Effects of Rotenone and Amytal

Inhibit Complex 1 of ETC

(22) Effect of Antimycin A

Inhibit Complex 3 of ETC

(22) Effects of Cyanide and Azide

Inhibit Complex 3 & 4 (Cytochrome Oxidase) of ETC

(22) Effects of brown adipose tissues

uncouples proton gradient with ATP synthesis for thermogenesis

(22) Effects of Ionophores

Collapse the proton gradient, resulting in increased cellular respiration and inhibiting ATP production

(22) Cellular respiration

processes by which cells consume O₂ and produce CO₂. In these processes, organic fuel molecules, such as glucose, fatty acids, and amino acids, are oxidized; the energy released from these oxidation processes is converted to bioenergy and stored in ATP

(22) NADH and FADH₂

main sources of the reducing equivalents (collection/gaining of electrons)

(22) Pyruvate

Product of glycolysis that is then transported into the mitochondria and is converted to acetyl CoA

(22) Function of Malate-Aspartate shuttle

brings electrons into the mitochondria at the NADH level

(22) Uncouplers

chemicals that collapse the proton gradient across the mitochondrial inner membrane; often carry protons across the mitochondrial inner membrane without producing ATP

(23) (34) Lactic Acidosis

Elevated concentrations of Lactate in blood, lowering pH. Causes include failure to regenerate NAD+ from NADH

(23) Anabolic pathways

synthesize complex molecules from simple molecules; consume energy

(23) Catabolic pathways

breakdown complex molecules to simple molecules; produce energy and building blocks for other biosynthetic processes

(23) Glycolysis

conversion of glucose to pyruvate; Does not need oxygen, but needs NAD+

(23) Ketosis

Process in which Accumulation of acetyl CoA results in the conversion of acetyl CoA to acetoacetyl CoA and other such condensation products called ketone bodies

(23) ketoacidosis

Medical condition in which Decreased availability of glucose during extreme starvation or in diabetic patients causes a very high level of ketone body production to occur due to increased breakdown of fatty acids

(23) Function of Urea cycle

to dispose the ammonium produced during amino acid catabolism

(23) Glycogen can supply:

~8-10 hours worth of energy

(23) Fat can supply:

between several days to a few weeks of energy

(23) Function of Pentose phosphate pathway (PPP)

Generation of reducing agents, in the form of NADPH, which are used in various reductive biosynthesis reactions within cells (e.g., fatty acid synthesis); and Production of ribose 5-phosphate (R5P), used in the biosynthesis of nucleotides and nucleic acids

(23) Insulin

storage hormone Produced by the pancreatic β cells; Most active after feeding. Stimulates uptake of glucose by cells, glycogen synthesis (glycogenesis), lipogenesis, protein synthesis, inhibits lipolysis, and stimulates glycolysis after feeding

(23) Glucagon

mobilizing hormone Produced by the pancreatic α cells; Most active during fasting (or a few hours after a balanced meal). Stimulates glycogenolysis and de novo glucose synthesis (gluconeogenesis) to increase blood glucose levels. Stimulates lipolysis and releases free fatty acids into blood

(23) Metabolic state - FED (2-4 hrs after a normal meal)

high insulin; low glucagon. Blood glucose is high (from diet), Taken up by liver/muscle and stored as glycogen, used by brain.

(23) Metabolic state - FAST (>4 hrs to a few days after a meal)

low insulin; high glucagon. Blood glucose is low, Liver breaks down glycogen and releases free glucose into the blood to be used for fuel.

(23) Metabolic state - STARVATION (>2-3 weeks after a meal)

low insulin; high glucagon. Glycogen is completely depleted, Liver synthesizes glucose from amino acids (via gluconeogenesis) and releases free glucose in blood for brain and red blood cells to use as energy

(33) Effects of Arsenate Poisoning

Incorporated into Glyceraldehyde-3-P instead of Phosphate, eliminating substrate level phosphorylation in glycolysis. No net gain of ATP.

(33) Effects of Fluoride

Inhibits enolase (and lactate production by bacteria)

(33) Pyruvate Kinase Deficiency

Normally adds a Phosphate to produce ATP; RBCs that have no mitochondria (for ETC) and rely entirely on glycolysis for ATP can experience hemolytic anemia.

(33) Lactate Dehydrogenase

Converts Lactate to Pyruvate for energy in the body

(34) Leigh Syndrome

Mutation in Pyruvate Dehydrogenase or Pyruvate Carboxylase causing lactic acidosis

(34) Pyruvate Dehydrogenase Complex (PDH)

Converts Pyruvate to Acetyl-CoA for biological processes

(34) E1 Deficiency

congenital lactic acidosis occurs because pyruvate is shunted to lactic acid via LDH. X-Linked Dominant

(34) Effects of Arsenite Poisoning

Inhibits enzymes requiring lipoic acid (including PDH, α-ketoglutarate dehydrogenase, branched-chain amino acid α–keto acid dehydrogenase) by forming stable complex with lipoic acid

(34) Berberi Disease and Wernicke-Korsakoff Syndrome

Deficient in Thiamine (Vitamin B1) which is a cofactor of PDH

(34) Effects of Fluoroacetate

Inhibits Aconitase, a protein used for TCA Cycle

(34) PDH kinase regulation of TCA Cycle

Inhibits E1, a component of PDH

(34) Pyruvate Carboxylase

Catalyzes the first reaction of gluconeogenesis. Activated by Acetyl-CoA (which is produced by PDH)

(36) von Gierke Disease

Glucose-6-Phosphatase deficiency, cannot release glucose into the blood so it accumulates in liver and kidney

(36) Cori Disease

Deficiency in de-branching enzyme so glycogen has abnormal structure, causing fasting Hypoglycemia

(36) McArdle Syndrome

Deficiency of Glycogen Phosphorylase particularly in skeletal muscle, therefore glycogen cannot be broken down to glucose during exercise

(34) PDH Phosphatase regulation of TCA Cycle

Activates E1, a component of PDH

(34) ATP, acetyl CoA, and NADH regulation of TCA Cycle

Activates PDH kinase, which inhibits E1 (cofactor of PDH), thereby also inhibiting PDH via feedback inhibition

(34) Pyruvate regulation of TCA Cycle

Inhibits PDH Kinase, allowing PDH to convert Pyruvate to Acetyl-CoA, thereby allowing TCA cycle to occur

(34) Ca2+ regulation of TCA Cycle

Released in skeletal muscles during contraction, stimulates PDH and energy production by activating PDH phosphatase

(34) Citrate, NADH, and Succinyl CoA regulation of Citrate Synthase

Inhibits Citrate Synthase via feedback inhibition

(34) Citrate Synthase

Synthesizes Citrate from Acetyl CoA and Oxaloacetate. 1st Rate-Determining enzyme of TCA Cycle

(34) Isocitrate Dehydrogenase

Oxidative decarboxylation reaction, yields the 1st NADH of TCA cycle and releases the 1st CO2. 2nd Rate-Determining Enzyme of TCA Cycle

(34) Activation of Isocitrate Dehydrogenase

ADP (a low energy signal) and Ca2+ (muscle contraction)

(34) Inhibition of Isocitrate Dehydrogenase

ATP and NADH (sufficient energy signals)

(34) α-ketoglutarate dehydrogenase

Causes oxidative decarboxylation and produces Succinyl CoA (which contains a high energy bond), the 2nd CO2, and produce the 2nd NADH

(34) Activation of α-ketoglutarate dehydrogenase

Ca2+ (muscle contraction)

(34) Inhibition of α-ketoglutarate dehydrogenase

ATP, GTP, NADH, and succinyl CoA (feedback inhibition)

(34) Cofactors of PDH and α-ketoglutarate dehydrogenase

thiamine, Lipoic acid, Coenzyme A (CoA), FAD, NAD

(34) Cofactors of Pyruvate Carboxylase

Contains biotin and requires ATP and Mg2+

(36) Fructosuria

Fructokinase deficiency

(18) Effect of Increased 2,3-BPG

Stabilizes T form of Hb to decrease its O2 affinity. Right shift SpO2 Curve