Genetics

Genetics

DNA bond strength (nucleotides)
Crazy Glue”:
Strongest bonds are between Cytosine and Guanine, strong like Crazy Glue (3 H-bonds), whereas the A=T only have 2 H-bonds.
This is relevant to DNA replication, as the weaker A=T will be the site where RNA primer makes the initial break.

Mitochondrial DNA (mt DNA) properties
mt DNA”.
mt stands for:
Maternal Transfer
Mutates Tremendously (high mutation rate)

tRNA: molecular shape
Fortunately, tRNA (Transfer RNA) is shaped like a capital T.

Pyrimidines are CUT from purines
Pyrimidines are Cytosine, Uracil, Thiamine and are one ring structures.
Purines are double ring structures.




Dicarboxylic acids (alpha, omega) from C2-C10
"Oh My, Such Good Apple Pie, Sweet As Sugar"
oxalic, malonic, succinic, glutaric, adipic, pimelic, suberic, azelaic, sebacic
Molecular Genetics
"EXons EXpressed, INtrons IN the trash"
DNA expression into mature mRNA
Pyrimidines are "CUT" from purines.
Pyrimidines are Cytosine, Uracil, Thiamine and are one ring structures. Purines are double ring structures.

Hemoglobin

Hemoglobin

Van den Bergh reaction (Jaundice test)
Indirect reacting bilirubinUnconjugated bilirubin”:
Both start with vowels, so they go together: Indirect & Unconjugated.

Heme synthesis: amino acid precursors to basic unit of porphyrins, heme (pyrrole ring)
“Dracula wants to Suck a Co-ed’s blood [think heme] with his Glystening teeth!”:
Succinyl CoA and Glycine are precursor amino acids to pyrrole rings, which is the basic unit of porphyrins and heme.

Hemoglobin binding curve: causes of shift to right
CADET, face right!”:
  • CO2
  • Acid
  • 2,3-DPG (aka 2,3 BPG)
  • Exercise
  • Temperature

Porphyrias: acute intermittent porphyria symptoms
5 P’s:
  • Pain in abdomen
  • Polyneuropathy
  • Psychologial abnormalities
  • Pink urine
  • Precipitated by drugs (eg barbiturates, oral contraceptives, sulpha drugs)

Sickle cell anemia: mutation
HbS isn’t Very Good”:
At Sixth position of HB beta chainValine is present instead of Glutamic acid.

Sickle cell disease pathophysiology
SICKle cell disease is due to a Substitution of the SICKsth amino acid of the B chain.

Vitamin K dependent cofactors
Several TenTo Nicely Stop Clots”:
Factor Seven, TenTwoNine.
Protein S, Protein C.

Coagulation common pathway: factors in order
10 + 5 – 2 = 13
Coagulation common pathway:
Factor to Factor to Factor II to Factor XIII

Hormones

Hormones

Adrenaline mechanism
ABC of Adrenaline”:
Adrenaline–> activates Beta receptors–> increases Cyclic AMP

Insulin: function
ININsul stimulates things to go
IN 2 cells: Potassium and Glucose.

Glucagon function
“Mr. Gluca has Gone to the cAMP to bring out some Glucose“:
Glucagon elevates glucose by cAMP mechanism.

Enzymes

Enzymes

Enzyme kinetics: competitive vs. non-competitive inhibition
With Kompetitive inhibition: Km increases; no change in Vmax.
With Non-kompetitive inhibition: No change in Km; Vmax decreases.

Enzymes: classification
Over The HILL“:
  • Oxidoreductases
  • Transferases
  • Hydrolases
  • Isomerases
  • Ligases
  • Lyases
Enzymes get reaction over the hill.

Enzymes: competitive inhibitors
Competition is hard because we have to travel more kilometers (Km) with the same velocity“:
With competitive inhibitors, velocity remains same but Km increases

Lipid

Lipid

Fabry’s disease
FABRY’S:
  • Foam cells found in glomeruli and tubules/ Febrile episodes
  • Alpha galactosidase A deficiency/ Angiokeratomas
  • Burning pain in extremities/ BUN increased in serum/ Boys
  • Renal failure
  • YX genotype (male, X linked recessive)
  • Sphingolipidoses
Phenylketonuria: which enzyme is deficient
PHenylketonuria is caused by a deficiency of:
Phenylalanine
Hydroxylase

Pompe’s disease: type
Police Po lys“:
Pompe’s disease is a lysosomal storage disease (alpha 1,4 glucosidase).

Pyruvate: products of complete oxidation
4 Naked Fun 3 Coeds1 Guy”:
Complete oxidation of pyruvate yields:
  • 4 NADH
  • FADH2
  • 3 CO2
  • 1 GTP

Protein

Protein

Catabolism steps of branched chain amino acids
Truck hit the Ox to Death”:
  • Transamination
  • Oxidative decarboxylation
  • Dehydrogenation

Essential amino acids
PVT. TIM HALL:
  • Phe
  • Val
  • Thr
  • Trp
  • Ile
  • Met
  • His
  • Arg
  • Leu
  • Lys
Pvt. is short for Private in the military.
Arg and His are considered semiessential.
Alternatively: “MATT VIL PHLy”.

Essential amino acids
PVT. TIM HALL always argues, never tires”:
  • Phe
  • Val
  • Thr
  • Trp
  • Ile
  • Met
  • His
  • Arg
  • Lue
  • Lys
Always argues: the A is for Arg, not Asp.
‘Never tires': T is not Tyr, but is both Thr and Trp.

Fasting state: branched-chain amino acids used by skeletal muscles
“Muscles LIVe fast”:
  • Leucine
  • Isoleucine
  • Valine
 AcetylCoA and acetacetylCoA: amino acids forming them
A Lighter Lease” (A LyTr LeIs):
  • A=AcetylCoA or Acetoacetyl CoA
  • Ly=Lysine
  • Tr=Tryptophan
  • Le=Leucine
  • Is=Isoleucine
BUN:creatinine elevation: causes
ABCD:
  • Azotremia (pre-renal)
  • Bleeding (GI)
  • Catabolic status
  • Diet (high protein parenteral nutrition)
Creatine phosphate: amino acid precursors
“Nice GAMs!”:
  • Glycine
  • Arginine
  • Methionine
Gam is slang for a person’s leg, especiallay an attractive female’s leg: “Nice gams = nice legs!”
Creatine phosphate is a muscle energy store, and spontaneously converts to creatinine which is excreted in the urine in direct proportion to muscle mass: clinically useful, such as in MS Dx.

Nitric oxide: amino acid precursor
When the dentist works on your teeth, you say, “AAArg! (Arginine)” before he administersNitric Oxide (NO) to take the pain away.
Other players necessary for NO synthesis: NO synthase, Ca++, NADPH.

Urea Cycle
Ordinarily, Careless Crappers, Are Also Frivolous About Urination.
  • Ornithine
  • Carbamoyl
  • Citrulline
  • Arginosuccinate
  • Aspartate
  • Fumarate
  • Arginine
  • Urea

Carbohydrate

Carbohydrate

Glycogen storage: Anderson’s (IV) vs. Cori’s (III) enzyme defect
ABCD:
Anderson’s=Branching enzyme.
Cori’s=Debranching enzyme.
Otherwise, can’t really distinguish clinically.
 
Glycogen storage: names of types I through VI
Viagra Pills Cause AMajor Hardon”:
  • Von Gierke’s
  • Pompe’s
  • Cori’s
  • Anderson’s
  • McArdle’s
  • Her’s
 Type 1 glycogen storage disease
Type = one (Von), ie Von Giereke’s disease

Glycolysis steps
Goodness Gracious, Father Franklin Did GBy Picking Pumpkins (to) Prepare Pies”:
  • Glucose
  • Glucose-6-P
  • Fructose-6-P
  • Fructose-1,6-diP
  • Dihydroxyacetone-P
  • Glyceraldehyde-P
  • 1,3-Biphosphoglycerate
  • 3-Phosphoglycerate
  • 2-Phosphoglycerate (to)
  • Phosphoenolpyruvate [PEP]
  • Pyruvate
‘Did’, ‘By’ and ‘Pies’ tell you the first part of those three: di-, bi-, and py-.
PrEPare’ tells location of PEP in the process.
Phosphorylation cascade: action during low glucose
“In the Phasted State, Phosphorylate”:
The phosphorylation cascade becomes active when blood glucose is low.
Citric acid cycle compounds
OCitric Acid IOf (course) A SiLly STupid Funny Molecule”:
  • Oxaloacetate
  • Citrate
  • Aconitate
  • Isocitrate
  • Oxalosuccinate
  • Alpha-ketoglutarate
  • SLucciny-CoA
  • STuccinae
  • Fumarate
  • Malate
SilLy and sTupid used to differentiate succinyL and succinaTe

Citric acid cycle compounds
Can I Keep Selling Sex For Money, Officer?”:
  • Citrate
  • Isocitrate
  • alpha Ketogluterate
  • Succinyl CoA
  • Succinate
  • Fumerate
  • Malate
  • Oxaloacetate
Citric acid cycle compounds
Oh! Can I Keep Some Succinate For Myself?”:
  • Oxaloacetate
  • Citrate
  • Isocitrate
  • Ketoglutarate
  • Succinyl coA
  • Succinate
  • Fumarate
  • Malate
Citric acid cycle compounds
Our CitIs Kept Safe And Sound From Malice”:
  • Oxaloacetate
  • Citrate
  • Isocitrate
  • alpha-Ketoglutarate
  • Succinyl-CoA
  • Succinate
  • Fumarate
  • Malate
Citric acid cycle compounds
Can I Ask Sharon Stone For MOrgasm?”:
  • Citrate
  • Isocitrate
  • Alpha-Ketoglutarate
  • Succinyl CoA
  • Succinate
  • Fumerate
  • Maleate
  • Oxaloacetate
Dicarboxylic acids (alpha, omega) C2 through C10: common names
OMy, Such Good Apple Pie, Sweet ASugar!”:
  • Oxalic
  • Malonic
  • Succinic
  • Glutaric
  • Adipic
  • Pimelic
  • Suberic
  • Azelaic
  • Sebacic
Galactosaemia: enzyme deficiency
GALIPUT:
Galactose 1 Phosphate Uridyl Transferase.
There is an assay called the Galiput test for this.
Hyperglycemia: 3 classic signs and symptoms
DKA
  • Dehydrated
  • Ketoacidosis
  • Acetone breath
Collagen concisely covered
COLLAGEN:
  • C-terminal propeptide (procollagen)Covalent Cross links/ vitaminConnective tissue/ Cartilage/ Chondroblasts/ Copper Cofactor (Covalent Cross linking)
  • Outside the cell is where collagen normally functions/ Osteoblasts/ Osteogenesis imperfecta
  • Lysyl hydroxylase/ Lysyl oxidase (oxidatively deaminates lysyl and hydroxylysyl residues to form collagen cross links, last biosynthesis step)
  • Long triple helical fibers/ Ligaments
  • Alpha chains/ Attached by H bonds form triple helix/ Ascorbate for hydroxylation of lysyl and prolyl residues of pro-Alpha chains (postranslational modification)
  • Gly in every third position/ Glycosylation of hydroxyl group of hydroxylysine with Glucose and Galactose; GOlgi allows procollagen to GO outside of cell
  • Extracellular matrix/ Eye (cornea, sclera)Ehlers-Danlos Syndrome
  • N-terminal propeptide (procollagen)Nonhelical terminal extensions
Note: Procollagen LEAVEs the cell to be cLEAVEd by procollagen peptidases
G6PD: oxidant drugs inducing hemolytic anemia
AAA:
  • Antibiotic (eg: sufamethoxazole)
  • Antimalarial (eg: primaquine)
  • Antipyretics (eg: acetanilid, but not aspirin or acetaminophen)
Carbon monoxide: electron transport chain target
“CO blocks CO”:
Carbon monoxide (CO) blocks Cytochrome Oxidase (CO) 
Electron transport chain: Rotenone’s site of action
Rotenone is a site specific inhibitor of complex one.
Malate-aspartate shuttle
MAD commute”:
Malate in.
Alpha-ketoglutarate and (Aspartate) out.






Glycolysis
Goodness (Glucose)
Gracious, (Glucose-6-P)
Father (Fructose-6-P)
Franklin (Fructose-1,6-diP)
Did (Dihydroxyacetone-P)
Go (Glyceraldehyde-P)
By (1,3-Biphosphoglycerate)
Picking (3-phosphoglycerate)
Pumpkins (2-phosphoglycerate)
(to)
PrEPare (Phosphoenolpyruvate [PEP])
Pies (Pyruvate)
Citric Acid Cycle
Oh (Oxaloacetate)
Citric (Citrate)
Acid (Aconitate)
Is (Isocitrate)
Of course (Oxalosuccinate)
A (Alpha-ketoglutarate)
SiLly (Succinyl-CoA)
STupid (Succinate)
Funny (Fumarate)
Molecule (Malate)