Usmle Step 1: Biochemistry 2

Front 1

Microtubule

Back 1

- Cylindrical strucutre composed of a helical array of polymerized dimers of alpha- and beta-tubulin. Each dimer has 2GTP bound. Incorporated into flagella, cilia, mitotic spindles. Grows slowly, collapses quickly. Microtubules are also involved in slow axoplasmic transport in neurons.

Front 2

Chediak-Higashi syndrome

Back 2

- due to a microtubule polymerization defect resulting in decreased phatocytosis

Front 3

cilia structure

Back 3

- 9 + 2 microtubule arrangement
- dynein is an ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets
- dynein = retrograde to microtubule (+ → −)
- kinesin = anterograde to
microtubule (− → +)

Front 4

Kartagener's syndrome

Back 4

Immotile cilia due to a dynein arm defect. Results in male and female infertility (sperm immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not pushed out); associated with situs inversus.

Front 5

Plasma membrane composition

Back 5

- asymmetric fluid bilayer
- contains cholesterol (~50%), phospholipids (~50%), sphingolipids, glycolipids, and proteins
- high cholesterol or long saturated fatty acid content →↑ melting temperature, ↓ fluidity

Front 6

Phosphatidylcholine (lecithin) function

Back 6

- major component of RBC membranes, of myelin, bile, and surfactant
- used in esterification of cholesterol

Front 7

Sodium pump

Back 7

- for each ATP consumed, 3 Na go out and 2 K come in
- during cycle, pump is phosphorylated

- Ouabain inhibits by binding to K site
- Cardiac glycosides (digoxin/digitoxin) also inhibit the Na/K ATPase, causing ↑ cardiac
contractility.

Front 8

Collagen

Back 8

- Type 1: bone, skin, tendon, dentin, fascia, cornea, late wound repair
- Type 2: cartilage, vitreous body, nucleus pulposus
- Type 3: reticular fibers, skin, blood vessels, uterus, fetal tissue, granulation tissue
- Type 4: Basement membrane or basal lamina

- Be Cool Read Books
- Bone, Cartilage, Reticulin, BasementMembrane

Front 9

Ethlers-Danlos syndrome

Back 9

- Faulty collagen synthesis causing hyperextensible skin, tendancy to bleed (bruising), hypermobile joints
- Type III collagen is most frequently affected (resulting in blood vessel instability)

Front 10

Osteogenesis imperfecta

Back 10

- variety of gene defects; all result in abnormal collagen synthesis (Type I most common)

- multiple fractures occuring w/ minimal trauma(brittle bone disease)
- blue sclera due to translucency of the connective tissue over choroid
- hearing loss (abnormal middle ear bones)
- dental imperfections due to lack of dentin

Front 11

Elastin

Back 11

- stretchy protein within lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae)
- tropoelastin w/ fibrillin scaffolding

Front 12

S-adenosyl-methionine

Back 12

- ATP + methionine → SAM
- SAM transfers methyl units (SAM the methyl donor man)
- regeneration of methionine (and thus SAM) is dependent on vit B12 and folate.

Front 13

Universal electron acceptors

Back 13

- nicotinamides (NAD+, NADP+) and flavin nucleotides (FAD+)
- NAD+ is generally used to catabolic processes to carry reducing equivalents away as NADH
- NADPH is used in anabolic processes (steroid/fatty acid synthesis) as a supply of reducing equivalents

Front 14

Hexokinase

Back 14

- ubiquitous
- high affinity (low Km), low capacity (low Vmax), uninduced by insulin
- feedback inhibited by glucose-6-phosphate

Front 15

Glucokinase

Back 15

- liver and beta-cells of pancreas
- low affinity (high Km), high capacity (high Vmax), induced by insulin
- no direct feedback inhibition
- phosphorylates excess glucose (e.g., after a mean) to squester it in the liver

Front 16

Glycolysis

Back 16

- glucose --> G6P --> F6P --> F1,6BP --> G3P + DHAP
- G3P --> 1,3-bis-phosphoglycerate --> 3-phosphoglycerate --> 2-phosphoglycerate --> Phosphoenolpyruvate (PEP) --> pyruvate --> acetyl-COA

- glucose --> G6P (via hexokinase)
- F6P --> F1,6P (via phosphofructokinase)
- PEP --> pyruvate (via pyruvate kinase)
- pyruvate --> acetyl-COA (via pyruvate dehydrogenase)

Front 17

Phosphofructokinase

Back 17

- catalyses F6P --> F1,6P (the rate limiting step of glycolysis)
- activated by AMP and F2,6P
- inhibited by ATP and citrate

Front 18

Pyruvate dehydrogenase

Back 18

- catalyses pyuvate --> acetyl-COA
- inhibited by ATP, NADH, acetyl-COA

Front 19

F2,6,BP

Back 19

- in fed state, phosphofructokinase 2 converts F6P into F2,6P
- F2,6P then activates phosphofructokinase 1

- F2,6BP is the most potent activator of phosphofructokinase (overrides inhibition by ATP and citrate) and is a potent regulator of glycolysis and gluconeogenesis.

Front 20

glycolytic enzyme deficiency

Back 20

- associated with hemolytic anemia by decreasing activity of Na/K ATPase, leading to RBC swelling and lysis
- RBCs metabolize glucose anaerobically and thusly depend solely on glycolysis

Front 21

Pyruvate dehydrogenase complex

Back 21

- the complex contains 3 enzymes that require 5 factors (first 4 B vitamins plus lipoic acid): pyrophosphate (B1), FAD (B2), NAD (B3), CoA (B5), lipoic acid

- activated by excersize: ↑ NAD+/NADH ratio, ↑ ADP, ↑ Ca2+
- arsenic inhibits lipoic acid leading to vomiting, rice water stools, and garlic breath

Front 22

Pyruvate dehydrogenase deficiency

Back 22

- causes backup of substrate resulting in lactic acidosis
- can be congenital or acquired (as in alcoholics due to B1 deficiency)
- treatment: ↑ intake of ketogenic nutrients (e.g., high fat content or ↑ lysine and leucine)

Front 23

Cori cycle

Back 23

- muscle tissue undergoes glycolysis converting glucose into pyruvate and then lactate
- muscle sends lactate to liver via bloodstream
- liver converts lactate to pyruvate then glucose via gluconeogensis
- liver sends glucose back to muscle via bloodstream

Front 24

TCA cycle

Back 24

- pyruvate --> acetyl-COA
- acetyl-COA + oxaloacetate --> citrate --> isocitrate --> alpha-ketogluterate --> succinyl-COA --> succinate --> fumarate --> malate --> oxaloacetate

- Citrate Is Kreb's Starting Substrate For Making Oxaloacetate

Front 25

Electron transport chain and oxidative phosphorylation

Back 25

- 1NADH --> 3ATP
- 1FADH2 --> 2ATP

- electron transport inhibitors: directly inhibit electron transport, causing decreased proton gradient and block ATP synthesis (rotenone, CN-, antimycin A, CO)
- ATPase inhibitors: directly inhibit mitochondrial ATPase, causing an increased proton gradient, but no ATP is produced because electron transport stops (oligomycin)
- uncoupling agents: increase permeability of membrane, causing a decreased proton gradient and increased O2 consumption. ATP synthesis stops, but electron transport continues (2,4-DNP, aspirin, and thermogenin in brown fat)

Front 26

Pentose phosphate pathway (HMP shunt)

Back 26

- produces NADPH, which is required for fatty acid and steroid biosynthesis and for glutathione reduction inside RBCs

Front 27

G6P dehydrogenase

Back 27

- the rate-limiting enzyme in the HMP shunt
- deficiency leads to hemolytic anemia due to poor RBC defense against oxidizing agents

Front 28

Fructose intolerace

Back 28

- Hereditary deficiency of aldolase B (recessive). Fructose-1-phosphate accumulates, causing a ↓ in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis.
- symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
- treatment: must ↓ intake of both fructose and sucrose (glucose + fructose)

Front 29

Essential fructosuria

Back 29

- Involves a defect in fructokinase and is a benign, asymptomatic condition, since fructose does not enter cells.
- symptoms: fructose appears in blood and urine

Front 30

Galactosemia

Back 30

- Absence of galactose-1-phosphate uridyltransferase. Autosomal recessive. Damage is caused by accumulation of toxic substances (including galactitol) rather than absence of an essential compound.
- Symptoms: cataracts, hepatosplenomegaly, mental retardation.
- Treatment: exclude galactose and lactose (galactose + glucose) from diet.

Front 31

Galactokinase deficiency

Back 31

- Causes galactosemia and galactosuria, galactitol accumulation if galactose is present in diet.

Front 32

Lactase deficiency

Back 32

- Age-dependent and/or hereditary lactose intolerance (blacks, Asians) due to loss of brush-border enzyme.
- Symptoms: bloating, cramps, osmotic diarrhea.
- Treatment: avoid milk or add lactase pills to diet.

Front 33

Transport of ammonium by alanine and glutamine

Back 33

- muscle exports alanine which is taken up by the liver
- liver transfers the NH3 from alanine to glutamate
- glutamate is converted into urea

Front 34

Hyperammonemia

Back 34

- can be acquired (e.g., liver disease) or hereditary
- excess NH4+ depletes alpha-ketogluterate, leading to inhibition of TCA cycle
- treatment: benzoate or phenylbutyrate to lower serum ammonia levels

Front 35

Ammonia intoxication

Back 35

- tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision