Errors in First Aid for the USMLE (2007): Biochemistry

The following is from an email sent to the First Aid Team concerning errors/corrections/suggestions to their 2007 edition.

Biochemistry (reference: Lipincott’s Illustrated Biochemistry)

  1. P.79, Vitamins
    1. Fat soluble: in any deficiency of these vitamins, liver and egg yolk are a source in the diet.
    2. Tox: D>A>K>E, Vit D is Deadly (toxic), Vit A is Also bad.
    3. Synthesis by microbes: K and B12
    4. Antioxidant: C, E, and beta-carotene
    5. Liver storage: DAKE + B12
  2. P.79, Vitamin A (retinol)
    1. Excess – Arthralgias, fatigue, headaches (cerebral edema), skin changes…
  3. P.79, Vitamin B1 (thiamine)
    1. Diagnose: [up arrow] RBC transketolase activity after thiamine treatment.
  4. P.80, Vitamin B12 (cobalamin)
    1. In the right column under causes for B12 deficiency: “lack of intrinsic factor (pernicious anemia, total gastrectomy)”
  5. P.83, Chromatin structure:
    1. Heterochromatin – Condensed, transcriptionally inactive – methylated histones
    2. Euchromatin – Less condensed, transcriptionally active – acetylated histones
  6. P.84, Genetic Code features
    1. “Methionine encoded by only one codon (AUG).”
  7. P.85, DNA replication and DNA polymerase
    1. Within the replication bubble, only the lagging strand creates fragments. The description of DNA poly III elongating “until it reaches primer of preceding fragment,” while true for one leading strand meeting another replication bubble, confuses the issue here. I think it could read:
      1. “On the leading strand, elongates the chain by adding deoxynucleotides to the 3′ end until it reaches another replication bubble. When on the lagging strand, it performs the same action repeatedly as the replication bubble grows, creating Okazaki fragments.”
      1. This would of course have to be preceded by an explanation of the replication bubble that might also incorporate a definition and illustration of a helicase.
        1. Helicase – an enzyme that separates the two strands of DNA into single strands allowing for replication to occur. The position of these separated strands is called the replication fork.
        2. Replication bubble – area of DNA between two replication forks that marks the site of replication in each direction along a chromosome. There are several replication bubbles along the chromosome during DNA replication.
      1. To avoid confusion, state upfront that
        1. DNA poly III reads 3′-5′, makes 5′-3′ and proofreads 3′-5′ “Poly III proofs 3′ first.”
        2. DNA poly I reads 3′-5′, makes 5′-3′ and proofreads 5′-3′
  8. P.88, tRNA
    1. The figure is very confusing. The accompanying paragraph makes reference to syntheTase scrutinizing the amino acid before and after, but the figure shows only one syntheTase and one synthAse. Further, the image flips over its vertical axis for some reason, and the “AA” attached to the middle tRNA’a 3′ end is changed to a “Methionine-ACC” without explanation. The figure should be changed to clearly show:
      1. The first step is the attachment of a methionine to AMP (leaving PPi), creating an aminoacyl-AMP (not attached to tRNA).
      2. The second step is the attachment of the Met-AMP to the tRNA’s ACC site, creating an aminoacyl-tRNA (attached to tRNA).
      3. tRNA syntheTase and tRNA synthAse are two different proteins or two regions of the same protein.
  9. P.88, Protein synthesis
    1. Figure shows a eukaryotic ribosome while the description is of a ” 30S ribosomal subunit.”
  10. P.89, Cell cycle phases
    1. The description of Permanent cells suggests that “neurons, skeletal and cardiac muscle, RBCs” all “remain in Go, regenerate from stem cells.”
  11. P.91, Cilia structure
    1. Iinclude the following:
      1. Dynein = retrograde (towards nucleus)
      2. Kinesin = anterograde (from nucleus )
  12. P.91, Kartagener’s syndrome
    1. Include the following: “…male and female infertility (sperm immotile, immotile fallopian cilia)…”
  13. P.95, Hexokinase vs. glucokinase
    1. Glucokinase is found in the liver and the Beta cells of the pancreas.
  14. P.96 , Regulation by F2,6BP
    1. This is a difficult concept. In the figure, the arrows are pointing in the wrong directions, i.e. PFK-2 is shown dephosphorylating F(1,6)BPate into fructose-6-P. The problem with most diagrams is that it is difficult to take into account the following in a single picture:
      1. Fed and Fasting states
      2. PFK-2 and F2,6BPase (the bifunctional protein’s two states of activity)
      3. Stimulation of glycolysis and inhibition of gluconeogenesis.
    2. To capture these three variables, you effectively need three circles in your diagram. This is my best effort at such a diagram. See below.
  15. P.96, Glycolytic enzyme deficiency
    1. “glucose phosphate isomerase (4%)” ??
  16. P.98, Electron Transport chain and oxidative phosphorylation
    1. The outcomes of the oxidative phosphorylation proteins are not correct.
      1. Electron transport inhibitors will cause a decrease in O2 consumption; this is not mentioned.
      2. ATPase inhibitors will cause an increase in O2 consumption; this is not mentioned.
      3. Uncoupling agents increase the permeability of the membrane to H+ ions; it is listed as decreasing permeability.
      4. Uncoupling agents will cause an increase in O2 consumption; it is listed as causing a decrease.
  17. P.99, Pentose phosphate pathway (HMP shunt)
    1. The two sentences beginning, “All reactions…” and “Sites: lactating…” are immediately repeated within the section. One should be deleted.
    2. The HMP shunt is locating in RBCs, allowing them to handle oxidative damage by replenishing glutathione. RBCs are excluded in the following sentence : “Sites: lactating mammary glands, liver, adrenal cortex – all sites of fatty acid or steroid synthesis.”
  18. P.100, Disorders of galactose metabolism
    1. Galactosemia ” is a symptom. Classic Galactosemia is the name of the disease described. In addition to the later symptoms of “cataracts, hepatosplenomegaly, mental retardation” the more immediate symptoms (not included) are galactosemia, galactosuria, vomiting, diarrhea, jaundice.
  19. P.101, Amino acids
    1. Everyone has there own take on which are and are not essential, but I’ve found the following to be useful:
      1. Conditionally Essential (3) “Babies CRY,” important early in life and during periods of growth.
        1. Cysteine (Cys), glucogenic
        2. aRginine (Arg), glucogenic
        3. t Yrosine (Tyr), gluco/ketogenic
  20. P.101, Transport of ammonium by alanine and glutamine
    1. I found the layout of these diagrams to be confusing. The first diagram does not indicate that B6-dependent AminoTransferases are involved with each exchange of the NH3, and the last step showing Glutamate going straight to Urea is incomplete. The interesting point about alanine transport versus glutamine transport is the different enzymes used and the different tissues involved, and the diagrams do not make this clear. Further, the second diagram shows glutamine transport of ammonium as ending with Aspartate and NH4. While these are the substrates for the Urea Cycle, Glutamine is the amino acid donating the NH4 in Glutamine Transport. Lipincott’s Illustrated Biochemistry has a great diagram on P.251 (3rd Ed).
  21. P.101, Transport of ammonium by alanine and glutamine:
    1. Treatment: Arginine should include (see Urea Cycle).
  22. P.102, Phenylketonuria
    1. The diagram shows a double arrow, implying that THB to DHB is a reversible reaction through Phenylalanine Hydroxylase (PAH). This is not the case. I also feel that this section should address that elevated levels of Phe are what cause the side effects, and that this can come from a deficiency of maternal or fetal PAH. I think the following table should be included (see below).
  23. P.102, Alkaptonuria
    1. This section does not make mention of the striking symptom of black/blue cartilage of the nose, cheek, ear, and splotches in the sclera. I think it should be changed to:
      1. Congenital deficiency of homogentisate acid oxidase in the degradative pathway of tyrosine; often benign. Resulting alkapton bodies deposited in various connective tissues may result in
        1. Erosion of large joint cartilage, causing debilitating arthralgias
        2. Blue/black discoloration of cartilage in the nose, cheek, eyes and black splotches of the sclera
        3. Urine that turns black on standing.
  24. P.103, Homocystinuria
    1. The neat thing about this pathway is that a block at cystathionine synthase can be treated with vitamins to reverse or continue the pathway and that a build up of homocysteine is associated with the side effects. I think this section should be changed to reflect this:
      1. 3 forms (all autosomal recessive):
        1. Cystathionine synthase deficiency (treatment: [down arrow] Met, [up arrow] Cys, [up up arrow] B12 and [up up arrow] folate in diet)
        2. [down arrow] affinity of cystathionine synthase for pyridoxal phosphate (treatment: [up up arrow] B6 in diet)
        3. Homocysteine methyl transferase deficiency
      1. Results in [up arrow] HomoCys, [up arrow] Met and [down arrow] Cys in blood and urine. Cys becomes essential.
      2. Side Effects: mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), and atherosclerosis (stroke and MI; associated with [up arrow] HomoCys)
  25. P.103, Maple syrup urine disease
    1. The severe side effects of this disease only occur if left untreated. Patients with this disease typically present early in infancy. I think the following should be added:
      1. Classic type presents in infancy with difficulty feeding, vomiting, dehydration and severe metabolic acidosis. Diaper smells of “burnt sugar.”
  26. P.104, Purine Salvage Pathway:
    1. Arrows show AMP going to IMP in two steps; IMP going to AMP in one step. This is backwards.
    2. Could mention that Allopurinol inhibits Xanthine Oxidase here.
  27. P.105, Insulin
    1. The diagram with all of its +’s and -’s is confusing and requires time to “translate” what it means for the phosphorylation/dephosphorylation of the enzymes shown. I’ve attached a diagram that shows the controls and also makes the regulators unique to the liver and muscle more obvious. See below.
  28. P.105, Glycogen
    1. Enzyme converting Glucose-1-phosphate to UDP-glucose is incorrectly labeled as Glycogen Synthase (should be UDP-glucose phosphorylase). Glycogen synthase is involved in the next step for extending the chain of glycogen.
  29. P.106, Glycogen storage diseases
    1. Deficient enzyme in Von Gierke’s is listed as “Glucose-6-phosphate.” Should be “Glucose-6-phosphatase
  30. P.111, Heme Synthesis
    1. This drawing shows Lead inhibiting ALA synthetase.
    2. Lead inhibits ALA hedehydratase and ferrochelatase, not ALA synthetase (correctly noted in following section, Porphyrias).
    3. Heme -> Hemin -> inhibits ALA synthetase. This is a great feedback inhibition and represent the emergency treatment of porphyrias, i.e., the administration of IV Hemin.
    4. In the right margin, it should mention that this pathway is in the liver (P450) and Bone Marrow (hemoglobin synthesis). This is why phenobarbital, griseosulvin, etc can cause attacks of porphyria, by inducing the increased expression of P450, increased need for Heme, and exacerbation of deficiency.
  31. P.111, Porphyrias
    1. In addition to the “5 P’s” of Porphyria, I suggest making an addition
      1. Painful Abdomen
      2. Pink Urine
      3. Polyneuropathy
      4. Psychological disturbances
      5. Precipitated by drugs
      6. Pruritis
      7. Photosensitivity

Maternal PKU and Fetal PKU

Return to First Aid Errors page.

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9 Responses to Errors in First Aid for the USMLE (2007): Biochemistry

  1. Virginia says:

    For the porphyrias — I think those 5Ps correspond just to the acute intermittent porphyria, which doesn’t have photosensitivity or pruitis as symptoms. Great website, this cleared up a lot of confusion.

    -Virginia

  2. Lindsay says:

    Page 109, diagram of chylomicrons. Shouldn’t have Apoprotein A–A is found only on HDL particles.

  3. Lindsay says:

    On second reading, perhaps CM do contain Apo A, but HDL seems to be the main location of Apo A.

  4. Sruthi says:

    Thank you for posting your findings. Here’s another:

    P 92: In both Lipp Biochem (p47) and High Yield Histo (ch 5- p 45)say that both hydroxylation and glycosylation occur in the RER as does formation of the of procollagen (triple helix) from pro-alpha-collagen. In First Aid it says Glycosylation and procollagen formation occurs in the Golgi.

    Do you agree?

  5. Fernando says:

    Page 112. Hemoglobin modifications. On the right it says, “Administer nitrates in cyanide poisoning to oxidize hemoglobin to methemoglobin.” This should be nitrites, not nitrates.

  6. Shining says:

    What is the deal with on the bottom of page 104, where in the “Fasting State” diagram, glycerol is being converted into DHAP, and then through the TCA cycle into acetyl CoA? Wouldn’t glycerol converted to DHAP be used directly for gluconeogenesis in the fasting state? In any case, how would DHAP be converted into Acetyl CoA by means of the TCA cycle?

  7. Pablo Dreiss says:

    Lots of Fantastic information in your blogpost, I favorited your blog post so I can visit again in the future, Thanks

  8. axia ecampus says:

    axia ecampus

    Errors in First Aid for the USMLE (2007): Biochemistry | the rumors were true

  9. Thank you very much for this information , I will certainly use them

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