USMLE Biochemistry Part 2 (JR)

lovilope's version from 2018-04-07 20:33


Dbone mineralization & calcium absorption
C (Ascorbic Acid)scurvy
B1 (ThiamineBeri-Beri
B2 (Riboflavin)FAD
B3 (Niacin)NAD, Pellagra --> 3Ds = Dermatitis, Diarrhea, Dementia
B5 (Pentothenate)CoA
B6 (Pyridoxine)ALT, AST, used to treat neurotoxicity, decarboxylation of glutamic acid to GABA, transamination, synthesis of niacin
B7 (Biotin)carboxylation, add CO2 groups
B9 (Folic Acid)absorbed in jejunum, macrocytic, hyperchromic, megaloblastic anemia
B12 (Cobalamin)absorbed in ileum, macrocytic megaloblastic anemia + hypersegmented PMNs, "methyl folate trap" caused by B12 deficiency

Amino Acids

Question Answer
Essential AAsPVT TIM HALL (phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, arginine, leucine, lysine)
Acidic AAsAspartic acid, Glutamic Acid
Basic AAshistidine, leucine, arginine
Ketogenic AAsPVT TIM HALL (leucine, lysine)
Nuclear Localizing Signal AAsAPL (arginine, proline, lysine)
Golgi AAsTSA (Threonine, Serine, Asparagine)

Amino Acid Derivatives

Question Answer
PhenylalanineTyrosine (+ Iodide = Thyroxine) --> DOPA (Melanin = substantia nigra) --> Dopamine --> NE --> Epi (cleave NOR to from Epi)
TryptophanNiacin (B3) & Serotonin --> Melatonin (requires B6)
HistidineHistamine (requires B6)
GlycineProphyrin --> Heme (requires B6)
Arginine (BUN)Creatinine, Urea, NO
GlutamateGABA, Glutathione (requires B6)


Question Answer
Creatinine, NO, UreaArginine
Niacin, Serotonin, MelatoninTryptophan
Porphyrin, HemeGlycine
GABA (γ-Aminobutyric acid), GlutathioneGlutamic Acid
DOPA, Dopamine, NE, Epi
Negative Nitrogen Balance
Phenylalanine, Tyrosine
Treat with Threonine

AA disorders

Question Answer
Phenylketouria (PKU)↓ phyenyalanine hydroxylase or ↓ tetrahidrobiopterin (THB). ↑ phenylalanine in body "MUST BODY ODOR"= mental/growth retardation, seizures, fair skin (↓ melanin), musty body odor. Tx = ↓phenylalanine, ↑tyrosine, ↑THB
Alkaptonuria (Ochronosis)↓homogenistic acid oxidase (↑ homogenistic acid). Can't breakdown tyrosine. Signs = dark CT, brown sclera, urine turns black, arthralgias
Albinism↓Tyrosinase (can't make Melanin), ↓Neural crest migration. ↑ risk of skin cancer
Homocystinuria↓cystathionine synthase or ↓homocysteine methyltransferase, ↓B12, ↓Folate, ↓B6. ↑↑ homocysteine in urine, lens dislocation (also seen in Marfan's), tall height, mental retardation, high risk of MI and stroke
Cystinuriadefect in COLA transporter in PCT of kidney. COLA = cystine, ornithing, lysine, arginine. ↑cystine in urine = hexagonal crystals. Tx = ACetalzolamide (carbonic anhydrase inhibitor = ↑ pH in urine)
Maple syrup dzI LuV maple syrup (branches). ↓alpha-ketoacid dehydrogenase. Urine smells like maple syrup.
Hartnup dz

Pernicious anemia
↓neutral AA transporter in kidneys & enterocytes. Tryptophan wasting in urine. ↓tryptophan = ↓B3 (Niacin) = 3D's (Dermititis, Dementia, Diarrhea) --> Pellegra. Can be treated with niacin and high protein diet. Presents as skin rash

Large erythrocytes with methylmalonic acid in urine

Catecholamine Synthesis

ProcessEnzymes + Cofactors
Phenylalanine to TyrosinePhenylalanine Hydroxylase + tetrahydrobiopterin (BH4)
Tyrosine to DOPATyrosine Hydroxylase + tetrahydrobiopterin (BH4)
DOPA to DopamineDOPA decarboxylase + B6 (PYRIDOXINE)
Dopamine to NEDopamine beta-hydroxylase + Vitamin C
NE to EpiPhenylethanolamine N-methyltransferase + SAM (sam donates a methyl group)

Breakdown products of catecholamines (via MAO or COMT)

Question Answer
NENormetanephrine --> VMA

Urea Cycle

Break down of AAs --> metabolites (pyruvate, acetyl-CoA) + side product (NH4+ = converted to urea and excreted by kidneys)


Question Answer
Rate limiting enzyme for Urea CycleCarbamoyl Phosphate Synthetase I (mitochondria, uses nitrogen from NH4+)
**Rate limiting enzyme for Pyrimidine SyntesisCarbamoyl Phosphate Synthetase II (cytosol, uses nitrogen from glutamine)
Ornithine Transcarbamylase Deficiencymost common urea cycle defect, can't excrete ammonia (NH3+). Excess Carbamoyl Phosphate --> ↑ Orotic Acid. ↓ BUN (b/c ↑ Urea production). HYPERAMMONEMIA (↑NH3+)
Hyperammonemia (HEPATIC ENCEPHALOPATHY)↑NH3+ in the body. Depletes alpha-ketoglutarate --> ↓TCA. Signs = tremor (asterixis), slurred speech, vomit, cerebral edema, blurry vision. Tx = Benzoate or Phenybutyrate or Lactulose
Benzoate or Phenylbutyratebind AAs and lead to secretion
Lactulosesugar, can't be absorbed by enterocytes, in GI tract metabolized by bacteria, ↓ ph (more acidic = proton donor) --> NH3+ converted to NH4+ (ammonium) --> NH4+ can't be reabsorbed --> excreted -> ↓NH3+ levels

Heme Synthesis

DiseaseAffected EnzymeAccumulated SubstratePresenting Symptoms
Lead poisoningFerrochelatase and ALA dehydrataseProtoporphryin (blood)Microcytic anemia, GI and kidney disease. Mental deterioration, headache, memory loss, demyelination. Think lead paint, and battery/ammunition/radiator factory for exposure.
Acute intermittent porphyriaPorphobilinogen deaminase (urophorphyrinogen-I-synthase)Porphobilinogen, ALA, uroporphyrin (urine)Painful abdomen, pink urine, polyneuropathy, psychological disturbances, precipitated by drugs. Treat with glucose and heme to inhibit ALA synthase
Porphyria cutanea tardaUroporphyrinogen decarboxylaseUroporphyrin (tea-colored urine)Blistering cutaneous photosensitivity. Most common porphyria

Heme synthesis pathway

Item Next
Glycine and Succinyl CoA (+B6. Rate limiting step. ALA synthase)Alpha-aminolevulinic acid (+ALA dehydratase)
Alpha-aminolevulinic acid (+ALA dehydratase)Porphobilinogen (+Porphobilinogen deaminase)
Porphobilinogen (+Porphobilinogen deaminase)Hydroxymethylbilane
HydroxymethylbilaneUrophorphyrinogen III (+Urophorphyrinogen decarboxylase)
Urophorphyrinogen III (+Urophorphyrinogen decarboxylase)Coproporphyrinogen III
Coproporphyrinogen IIIProtoporphyrin (+Fe, Ferrochelatase)
Protoporphyrin (+Fe, Ferrochelatase)last


Glycine + Succinyl CoAALA synthase (with B6). Rate limitingSideroblastic anemia (XR)
ALAALA dehydrataseLead poisoning
PorphobilinogenPorphobilinogen deaminaseAcute intermittent porphyria
Uroporphyrinogen IIIUroporphyrinogen decarboxylasePorphyria cutanea tarda
ProtoporphyinFerrochelatase (+Fe)Lead poisoning



Question Answer
1DNA (negative charge) --> loops around HISTONES (positive charge, Lysine & Arginine). H1 = ties nucleosomes together (not in the core)
HeterochromatinHighely Condensed, can't undergo transcription
Euchromatinless condensed, TRANSCIPTIONALLY ACTIVE
DNA methylationtemplate DNA (C & A) add methyl - can distinguish b/w old and new strands
Histone methylationMUTES DNA
Histone acetylationACTIVATES DNA ((relaxes DNA coiling, allows transciption)


Question Answer
PurineA,G (ketone)
PyrimidineC,U,T (methyl)
C-G bonds3
Purine synthesisGAG+THF + CO2. (GAG = glycine + aspartate + glutamine). Carbon = CO2, THF, Glycine
Pyrimidine synthesisAG+THF + CO2 (AG = aspartate + glutamine). Carbon = CO2, Aspartate
Nucleosidebase + Sugar
Nucleotidebase + sugar + phosphaTe

Pyrimidine Synthesis (C,U,T)

Question Answer
Step 1start w/ base (OROTIC ACID)
Step 2add sugar + phosphate (PRPP)
Overallmodify base
RLECarbamoyl Phosphate Synthetase II

Purine Synthesis (A,G)

Question Answer
Step 1start w/ sugar + phosphate (PRPP)
Step 2add base
Overalladd base
RLEGlutamine PRPP-Aminotransferase

Purine Salvage/Synthesis (A,G); Pyrimidine Synthesis (C,U,T)

Pyrimidine & Purine Synthesis

Question Answer
Purines made from what precursor?IMP
Purine synthesis pathwaystart with Ribose 5P-->PRPP--> --> --> --> IMP--> AMP or GMP
Purine synthesis requires what?glycine, aspartate, glutamine, and THF
Pyrimidine synthesis pathwaystart with carbamoyl phosphate--> --> -->orotic acid + PRPP---> UMP-->UDP-->dUDP + CTP--->dUMP-->dTMP, requires aspartate, thymidylate synthase, dihydrofolate reductase, ribonucleotide reductase
Orotic acid + PRPP --> UMP
N5, N10-methylene tetrahydrofolate reductase
UMP Synthase
Produces thymine nucleotide required for DNA synthesis
UDP --> dUDP enzymeRibonucleotide reductase
dUMP --> dTMP enzymeThymidylate synthase
DHF --> THF enzymeDHF reductase
Hydroxyureainhibits ribonucleotide reductase (no UDP-->dUDP)
Used for: Melanoma, Sickle cell disease (increases HbF)
S.E.: Myelosuppression
6-mercaptopurine6MP blocks de novo purine synthesis = Thiol analog
Used for: AML/ALL
S.E. increased toxicity w/ Allopurinol since 6-MP is metabolized by xanthine oxidase
6-thioguaninesame mechanism as 6MP - blocks de novo purine synthesis
Can be used w/ Allopurinol
5-fluorouracil5FU inhibits thymidylate synthesis (no dUMP--> dTMP
Used for: solid tumors (colon, breast, ovarian CA)
S.E.: irreversible myelosuppression --> give Thymidine; photosensitivity
Methotrexateinhibits dihydrofolate reductase so no dTMP
Used for: Liquid tumors (Leukemias); abortion, RA, psoriasis
S.E.: reversible myelosuppresion --> give Leucovorin (folinic acid); teratogenic

inhibits bacterial dihydrofolate reductase (less dTMP)
S.E.: Megaloblastic anemia, Leukopenia, Granulocytopenia (give Leucovorin)

Treats gout by inhibiting xanthine oxidase
Carbamoyl phosphateinvolved in 2 pathways for de novo pyrimidine synthesis and urea cycle
Ornithine transcarbamoylase deficiency (OTC)involved in urea cycle = takes carbamoyl phosphate to citrulline so leads to an accumlation of carbamoyl phosphate, this is converted to orotic acid-->aciduria
Findings = increased orotic acid w/ hyperammonemia
Orotic aciduriano conversion of orotic acid--> UMP due to defect or deficiency in orotic acid phosphoribosyltransferase or decarboxylase
autosomal recessive
Findings = orotic acid in urine, megaloblastic anemia (doesn't improve with B12 supplement), CRYSTALS IN THE DIAPER...NO hyperammonemia
treat w/ oral uridine
HGPRTenzyme for transferring guanine or hyoxanthine on to phosphoribose to form purine nucleotides in purine salvage = Lesch Nyhan Syndrome
Adenosine deaminase deficiencyexcess ATP/dATP imbalances nucleotide pool via feedback inhibition of ribonuc reductase-->prevents DNA synth-->decreased lympho count, **1 of major causes of SCID**
SCIDcan be caused by adenosine deaminase deficiency - adenosine builds up and is toxic to WBCs
treated by gene therapy
Lesch Nyhan syndrome

Von Gierke's Syndrome
XR deficiency of HGPRT which converts hypoxanthine-->IMP and guanine-->GMP, excess uric acid production--> retardation (brain relies on salvage pathway), self mutilation, aggression, gout, choreoathetosis
Characterized by hypoglycemia, Hyperlipidemia, Ketosis and Lactic Acidosis

DNA Replication

Question Answer
Helicaseunwinds DNA at replication fork
Single-stranded binding proteinsprevents the two unwound DNA strands from reannealing
DNA topoisomerases (Gyrase)relieve strain on the segment (before the helicase)
DNA topoisomerase Icut one strand of DNA = prevent strain & supercoils
DNA toposiomerase IIcut both strands to allow second double-stranded helix to pass through, also afterwards JOINS the cut strands (inhibited by Fluroquinolones)
Primasemakes an RNA primer on which DNA polymerase III can start replication
DNA polymerase IIIprokaryote only. elongates leading strand starting at 3'end. elongates lagging strand until it reaches primer. SYNTHESIS = 5'-3' end
Exonuclease 3'-5'DNA polymerase III
Exonuclease 5'-3'DNA polymerase I
DNA polymerase Iprokaryote only. degrades RNA primer; replaces w/ DNA.
catalyzes lagging strand DNA in eukaryotesDNA polymerase alpha
catalyzes leading strand DNA synthesis in eukaryotesDNA polymerase delta
catalyzes mitochondrial DNA synthesis in eukaryotesDNA polymerase gamma
repair DNA in eukaryotesDNA polymerase beta & gamma
direction polymerases read template DNA strands?3' to 5'
direction polymerases write/assemble new DNA strands?5' to 3'
when an acid sequence is written out, assume that it starts at the ___ end unless it says otherwise5'
DNA ligaseseals bonds within a strand of double stranded DNA
Telomeraseadds DNA to 3' end to avoid loss of genetic material
Nucleotide excision repairendonuclease (remove damaged nucleotides), DNA polymerase (fill gap), Ligase (seal) FIX THYMIDINE DIMERS Dz = XERODERMA PIGMENTOSUM
Base excision repairglycosylase recognize base (DEAMINATED) weird base, remove, fill, seal. important in spontaneous/toxic deamination
Mismatch repairmismatched nucleotides = remove, fill, seal. Dz = Hereditary Non-polyposis colorectal cancer (HNPCC)
Nonhomologous end joiningbring together 2 ends of DNA to repair double stranded breaks. Dz = ataxia telangiectasia
DNA & RNA synthesized5'-3'(5' of incoming nucleotide has the Triphosphate, gives energy for bond and can bind to the 3' Hydroxyl Group of the forming chain)
tRNA synthesis3'-5'; have CCA at 3' end
5' endhas the phosphate group
3' endhas the base group
mRNA is read3'-5'
Protein SynthesisN-terminus (amino) --> C-terminus (carboxyl)