The production of NADH from ethanol metabolism

hyper-

production via glycogenolysis

phosphorylation

delete "themselves" as it is redundant with autophosphorylate

transmembrane

insulin secretory granules.

phases. The first phase, which is the immediate post-meal response, begins within two minutes of nutrient ingestion. Insulin secretory granules docked to the beta cell plasma membrane are readily available to be released in this first phase.

In the second phase, the undocked insulin secretory granules are part of the reserve pool and are mobilized for exocytosis and release of their contents, while additional insulin is synthesized in the beta cell. This second phase has a lower rate of insulin release and can last for an hour or more.

It is a polypeptide synthesized in the beta cells of the pancreas. Proinsulin is folded in the rough endoplasmic reticulum (RER) where disulfide bonds form. Proinsulin is transported to the Golgi and then to immature secretory granules where most of the proinsulin is cleaved to form A and B chains held together by disulfide bonds, and the C-peptide is released. Mature "insulin secretory granules" fuse with the plasma membrane, and mature insulin, C-peptide and a small amount of proinsulin is released outside the cell.

HbA2

HbA2 (alpha2, delta2).

HbA

Hemoglobin A2 (alpha2, delta2)

native gel

"Intact hemoglobin tetramers..." (this is a point of confusion for students who have run SDS gels that would separate a tetramer into monomers, so emphasizing that this is a native gel electrophoresis helps)

mutant). Compound heterozygous patients with beta-S and beta-C alleles are designated as HbSC. This combination of allelic variants is also considered a sickle cell anemia, although much less severe than HbSS. Hemoglobin C disease (HbCC) is not a sickle cell anemia.

HbC

HbS

sickle cell trait.

Change to: "Combinations of Sickle Cell Trait and Thalassemia or other Hemoglobin Variants" (Other title is a little confusing because a patient would not have sickle cell disease and another mutation because with sickle cell disease, they would have either 2 beta-S alleles or 1 beta-S and 1 beta-C allele. HbSC is also considered a sickle cell anemia although much milder than HbSS. (HbCC is not a sickle cell anemia.)

HbA2 and HbC.

therapy

remove "FYI" as this was covered previously in the FMR block.

transduced with a lentiviral vector carrying a normally functioning beta-globin gene variant

was approved in 2019

hemoglobin

Bart (the apostrophe in the older Bart's is being dropped)

hemoglobin H (HbH, a tetramer of 4 beta-globin chains)

HbA

HbA2

HbA

HbF

HbA2

HbF

HbF

HbA2

Hb

HbE/b0

heterozygous

homozygous

HbF

HbA2

promotes nitric oxide production by an uncharacterized mechanism.

HbF

HbF, fetal hemoglobin

HbS

HbA

HbS (this is the standard naming convention)

Streptococcus (to be consistent with naming of all the pathogens listed; also the names should be italicized)

Hemoglobinopathies (remove word thalassemia or say "Combination Hemoglobinopathies including Thalassemias")

Combination Hemoglobinopathies (remove the word Thalassemia from this title)

alpha-globin chains

beta-globin chains

(Hemoglobinopathies)

Hemoglobin A, HbA

Hemoglobin A2, HbA2

Fetal Hemoglobin, HbF,

electrophoresis

functional beta

in patients

homotetramers of beta-like chains, either 4 gamma chains (Hb Bart) or 4 beta chains (HbH).

Homotetramers

delete word repetition

elevated

10 g/dL.

proteinuria

delete repeated words

a-splenic (if the word must be split between 2 lines)

beta-globin

heterozygous

homozygous

walls causing (remove hyphen)

delete "thus"

(E6V).

that

A deficiency in alpha- or beta-chains results in

(Globin gene duplication, either alpha- or beta-globin genes, can also cause an imbalance in the abundance of alpha- and beta-globin proteins, also resulting in pathology.)

mutations usually

delete hemoglobinopathies

chains, also called the alpha-globin gene cluster,

chains, also called the beta-globin gene cluster,

Section

progressive organ failure?

Note that aldosterone, the end product of the mineralocorticoid pathway, does not cause negative feedback inhibition on ACTH or CRH production.

spell out Adrenal Insufficiency in the table legend.

high

nodule

add space

increasing the expression of sodium channels, potassium channels, and the Na+/K+ ATPase in the distal tubule of the kidney.

binding

(DOC to corticosterone to 18-hydroxycorticosterone to aldosterone)

precursor

precursor

increase in sympathetic activity, and a decrease in NaCl passing through the renal nephron, as detected by the salt-sensing macula densa cells. (if "interesting" mechanistic text on a slide is not explained a little bit, it is very annoying for the students. But they can do without all the things that angiotensin II does for now.)

and starts with secretion of the protease renin from the juxtaglomerular cells of the kidney. Renin catalyzes the conversion of angiotensinogen, made in the liver, to angiotensin I that is converted to angiotensin II by the protease angiotensin-converting enzyme (ACE). (Students are often confused by and miss the fact that renin and ACE are proteases, so better to explain it here, as it is also illustrated in figure 4.)

as well as other peptides.

start new line- will increase list to 14 SLOs

Because of the similarity between TSH and a hormone that increases in pregnancy (human chorionic gonadotropin, hCG), a temporary gestational hyperthyroidism may develop with increasing hCG levels during pregnancy causing a thyrotoxicosis (discussed below).

same comment as earlier- TPO is located on the membrane. This figure 14 is also based on Figure 5, so if Fig 5 is changed, Figs 10 and 14 could also be changed.

While methimazole and propylthiouracil (PTU) both block thyroid hormone synthesis by inhibiting the PTO enzyme, PTU also inhibits peripheral T4 deiodination to active T3 so is used when a significant reduction in circulating thyroid hormone is required, as in a thyroid storm.

to be consistent with text, change to "Graves' disease" and add "gestational thyrotoxicosis" to the other causes of hyperthyroidism

Why is there a question mark in a box below the figure?

... or thyroid stimulating immunoglobulin, TSI)

autoimmune destruction of the pituitary (hypophysis) (lymphocytic hypophysitis)

Fig 10 does not show methimazole inhibiting TPO which is the drug target. This detail would connect this discussion with the one illustrated in Figure 5. If Figure 5 is redrawn as suggested, Fig 10 could also be redrawn, as it is based on Figure 5 information.

remove space

problem,

paragraph duplicates Table 3. Remove.

hyper- and

(T4)

...globulin, a carrier protein that binds to thyroid hormone in the blood.

reciprocal

and also

heterodimeric receptor

"nuclear receptor" superfamily

and other inactive metabolites

iodide

intracellular

the uptake of iodide via the sodium/iodide symporter, resulting in reduced organification and synthesis of thyroid hormone, a phenomenon...

as

anterior pituitary

"thyroglobulin by the apical plasma membrane protein thyroid peroxidase (TPO)," (Figure 5 is incorrect because TPO is on the plasma membrane, so it probably should be redrawn. However if it isn't redrawn, adding the above phrase may help with confusion over its location. If the figure 5 is redrawn, pendrin can be added on the membrane where iodide (add a negative charge on iodide I-) crosses the membrane to the colloid.)

iodide transport via pendrin protein,

Thyroglobulin is synthesized in the thyroid follicular cells and moved via exocytosis to the colloid space where it is stored. Iodide is moved from the follicular cell to the colloid via the anion transporter protein Pendrin. (Mutations in the pendrin gene can cause Pendred syndrome, with deficiencies in hearing and thyroid function).

iodinated thyroglobulin with the newly formed T4 and T3 residues.

a monoiodo- or diiodotyrosine side chain to DIT residues within thyroglobulin, to form a T3 or T4 residue in thyroglobulin, respectively.

iodinated

(DIT) within thyroglobulin.

remain part of the thyroglobulin protein at this point.

a sodium gradient resulting from the action of a

rotate figure 90o counterclockwise and enlarge to allow visibility of structure labels (can't see T3 vs T4 very well)

calcium and phosphate

an acellular, amorphous gel-like colloid that changes its density depending on the activity of the thyroid. The colloid portion of the thyroid contains nascent....

Are the labels on the figure inappropriately shifted to the right?

(< 0.005% of general population). Acquired nephrogenic DI may present in patients on long term lithium therapy, e.g., for bipolar disorder.

releases

(ADH) action. (Adding the word "action" covers ADH deficiency in pituitary DI as well as nephrogenic DI from vasopressin receptor (AVPR2) deficiency, and aquaporin (AQP2) deficiency.)

(aka, antidiuretic hormone, ADH)

with insulin in an "insulin tolerance test." (later in the chapter, this test is referred to in name, so the name should be given here.)

as discussed

that

change to: "so prolactin may be elevated in primary hypothyroidism if the lack of thyroid hormone feedback inhibition causes elevated TRH." (They didn't have thyroid yet, so the connection between low TH causing high TRH needs to be made here for them.)

(TRH)

Add: "Over-the-counter growth hormone may be used by body builders and athletes with the intention of increasing muscle mass; however the efficacy and long term effects are controversial." (Reword as you wish if you want to include this application- probably good for them to know people use this OTC, but I don't know if there is good data for its value.)

used

pituitary tumor

GH levels

glucose

as shown in the bottom image.

GH levels

glucose

explain what "TH" is on the graph. Maybe enlarge figure a bit to make it easier to see.

are

they require

comma within quotes

their

is this the prevalence in the US or world-wide?

period within quotes

GLUT4 translocation to the plasma membrane.

GH excess can cause high blood glucose (hyperglycemia), insulin resistance and diabetes mellitus.

glucose

glucose

glucose

Stimulates melanin synthesis and other functions

adrenocorticotropin hormone (ACTH)

remove semi-colon

Releases ACTH (adrenocorticotropin hormone/corticotropin), beta-endorphin, alpha-melanocyte stimulating hormone, and beta-lipotropin )

(termed releasing hormones (RH) or release inhibiting hormones (RIH))

(aka growth hormone release inhibiting hormone, GHRIH)

hormones (just to be consistent with naming - they are referred to as peptide hormones later)

thyrotropin releasing hormone (TRH)

It would be easier to see the text if you enlarge this figure.

catabolism?

catabolism?

do you mean hormone catabolism?

measure serum ACTH

anterior pituitary

anterior pituitary

(also commonly called "tropic" hormone)

one would

stimulating hormone produced by the pituitary,

absence or underdevelopment of the parathyroid glands

calcium/phosphate, respectively,

XRH

XH,

endocrine gland

"then causes negative or positive feedback to control..."

are present predominantly in the adrenal glands and gonads.

"mostly bound" The small percentage of unbound, free hormones are the active form.

anterior pituitary

such as during pregnancy,

binds

Change to "Receptors that activate the JAK-STAT pathway"

JAK-STAT is not a receptor. Ligands bind to a cell surface receptor and that activates the JAK-STAT pathway. So, this should be removed from that sentence or described separately, such as ..."and the cell surface receptors that activate the JAK-STAT pathway."

and they bind intracellular receptors in the "nuclear receptor" family.

The rate of clearance of a steroid hormone also affects the total concentration of the hormone in the cell.

catecholamines are not peptide hormones but are derived from an amino acid (tyrosine). Remove catecholamines from this sentence.

polypeptide