Biochemistry of hormones derived from amino acids and proteins
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Biochemistry of hormones derived from amino acids and proteins. Alice Skoumalová. Content Definition of peptide hormones Common features: synthesis, interactions with receptors at the cell surface Groups of peptide hormones

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Content proteins

  • Definition of peptide hormones

  • Common features: synthesis, interactions with receptors at the cell surface

  • Groups of peptide hormones

  • Hypothalamus-hypophysis hormonal cascade (signal amplification, negative feedback system)

  • Genes and formation of polypeptide hormones (gene superfamilies)

  • Hormones of the hypothalamus and the hypophysis

  • Synthesis and degradation of catecholamines

  • Biochemistry of parathyroid hormone and insulin

  • Degradation of peptide hormones

Definition of peptide hormones proteins

  • secreted into the blood stream; endocrine functions

  • synthesized from amino acids according to an mRNA template,

    which is itself synthesized from a DNA template

  • precursors (pre-prohormones) - posttranslational modification (endoplasmatic reticulum) - removal of the pre-sequence, sometimes glycosylation - resulting in prohormones

  • the prohormones - packaged into membrane-bound secretory vesicles - secreted from the cell by exocytosis in response to specific stimuli

  • mature peptide hormones diffuse through the blood to all of the cells of the body, where they interact with specific receptors on the surface of their target cells

G protein-coupled receptors cell surface

Signal transduction via:

1. Protein kinase A pathway (the elevation of cAMP activates protein kinase A)

Corticotropin releasing hormone, thyrotropin, luteinizing hormone, follicle stimulating hormone, adrenocorticotropic hormone, vasopressin, opioid peptides, norepinephrine, epinephrine

2. Protein kinase C and IP3-Ca2+ (inositoltriphosphate) pathway (triggering of the hydrolysis of phosphatidylinositol-4,5-bisphosphate and stimulation of protein kinase C)

Thyrotropin releasing hormone, gonadotropic releasing hormone, thyrotropin, norepinephrine, epinephrine, angiotensin

3. Protein kinase G pathway (the elevation cGMP activates protein kinase G)

Atrionatriuretic factor

Protein kinase receptors

e.g. Tyrosin specific protein kinases (Insulin)

Hormones cell surface

1. Amine-derived hormones

Catecholamines and thyroxine

2. Peptide hormones

Small peptide hormones(thyrotropin releasing hormone, oxytocin, vasopressin)

Protein hormones (insulin, growth hormone)

Glycoprotein hormones (luteinizing hormone, follicle-stimulating hormone and thyroid-stimulating hormone)

3. Steroid hormones

Peptide hormones cell surface

Hormones of the hypothalamus-hypophysis cascade

Hormones produced by other tissues

heart (atrionatriuretic factor)

pancreas (insulin, glucagon, somatostatin)

gastrointestinal tract (cholecystokinin, gastrin)

fat stores (leptin)

parathyroid glands (parathyroid hormone)

kidney (erythropoietin)

Hormonal cascade cell surfaceSignal amplification


Environmental or internal signal

Electrical-chemical signal

Limbic system

Electrical-chemical signal


Releasing hormones (ng)

Anterior pituitary

Anterior pituitary hormone (μg)

Target „gland“

The gonads, the thyroid gland, the adrenal cortex

Ultimate hormone (mg)

Systemic effects

CRH-ACTH-Cortisol cell surface

Environmental stress

A single stressor (change in temperature, noise, trauma)


Electrical-chemical signal

Limbic system

Electrical-chemical signal


Corticotropin releasing hormone (CRH) in ng, t1/2 minutes

Portal system

The corticotrophic cells

Anterior pituitary

Adrenocorticotropic hormone (ACTH) in µg, increased t1/2

Adrenal gland

Cortisol in mg, t1/2 hours

The glucocorticoid receptors in different cells

Systemic effects

Hormonal cascade cell surfaceNegative feedback system


Limbic system


Long feedback loop

Releasing hormones

Short feedback loop

Anterior pituitary

Anterior pituitary hormones

Target „gland“

Ultimate hormone

Systemic effects

Clinical correlation of the hormonal cascade cell surface

Testing the activity of the anterior pituitary

For example infertility: which organ is at fault in the hormonal cascade?

Step 1 The gonads must be considered

Step 2 The anterior pituitary must be tested

  • injecting LH or FSH

  • if sex hormone is elicited, the gonads function properly

  • i.v. administration of GnRH (secretion of LH and FSH; by RIA)

  • Normal response

  • The hypothalamus is nonfunctional

  • No response

  • The anterior pituitary is nonfunctional

Hypothalamus cell surface







Anterior pituitary













Adrenal cortex

Mammary gland




Skin darkening


Ovulation, corpus luteum, progesterone

Cell development, lactation


Hyperglycemic effects


Thyroid hormones

Interstitial cell development, testosterone

Development of follicles, estradiol

Growth of bone, body tissues; carbohydrate and protein metabolism; production of IGFs

Growth of seminal tubules and spermatogenesis

GH-Growth hormone, TSH-Thyrotropin, ACTH-Adrenocorticotropic hormone, LPH-Lipotropin,

MSH-Melanocyte stimulating hormone, PRL-Prolactin, FSH-Follicle stimulating hormone, LH-Luteinizing hormone

Hypothalamus cell surface


Axonal transport

Vasopressin (ADH)



Vasopressin (ADH)

Uterine contraction, lactation

Water balance

Vasopressin and oxytocin cell surface

  • Synthetized in the hypothalamus (nucleus supraopticus and paraventricularis)

  • Axonal transport with transport proteins (neurophysins)

  • Nonapeptides with disulfide bridge


Arginine vasopressin


Lysine vasopressin



Structural similarity, overlapping functions

Oxytocin: causes milk ejection in lactating female

Vasopressin: increases water reabsorption from distal kidney tubule

Hypopituitarism cell surface

  • The deficiency of one or more hormones of the pituitary gland

  • The connection between the hypothalamus and anterior pituitary can be broken by

    1. Trauma (automobile accidents)

    2. Tumor of the pituitary gland

  • Decreased generation of the pituitary hormones

  • A life-threatening situation

  • The usual therapy involves administration of the end organ hormones (cortisol, thyroid hormone, sex hormones, progestin, growth hormone in children)

Genes and formation of polypeptide hormones cell surface

Genes for polypeptide hormones contain the information for the hormone

1. More than one hormone is encoded in a gene

Proopiomelanocortin peptide family

Vasopressin and neurophysin II; oxytocin and neurophysin I

2. Multiple copies of a hormone are encoded in a gene

e.g. Enkephalins

3. Only one hormone is encoded in a gene

e.g. CRH

Proopiomelanocortin (a single gen product) is a precursor peptide for eight hormones

  • ACTH, β-lipotropin, γ-lipotropin, γ-MSH, α-MSH, CLIP, β-endorphine, enkephalins

  • Proopiomelanocortin occurs in both the corticotropic cells of the anterior pituitary and the pars intermedia cells, the products are different

CLIP-corticotropin-like intermediary peptide

Proopiomelanocortin peptide family peptide for eight hormones

  • Contains hormones (ACTH, LPH, MSH) and neurotransmitters

  • Precursor molecule involves 285 amino acids

  • Gene expression in the anterior and intermediary pituitary, but also in other tissues (intestine, placenta, male reproductive system)

  • Cleavage into peptides, further modification (glycosylation, acetylation, phosphorylation)

ACTH: acts on cells in the adrenal gland to increase cortisol production and secretion; excessive formation-Cushing‘s syndrome

β-lipotropin: induces lypolysis, precursor of β-endorphine

Endorphines: endorphines bind to the opioid receptors in CNS, analgesia

MSH: acts on skin cells to cause the dispersion of melanin (skin darkening)

Tyr-Gly-Gly-Phe-Met (methionine-enkephalin)

Tyr-Gly-Gly-Phe-Leu (leucine-enkephalin)

  • Model of enkephalin precursor

  • encodes several met-enkephalins (M) molecules and a molecule of leu-enkephalin (L)

  • Growth hormone (GH) peptide for eight hormones

  • synthesized in the adenohypophysis, the concentration in the pituitary is 5-15 mg/g

  • single polypeptide, two disulfide bridges

  • is essential for postnatal growth

Biochemical actions

1. GH increases protein synthesis

2. Carbohydrate metabolism: GH antagonizes the effects of insulin (hyperglycemia); decreased peripheral utilization of glucose, increased hepatic production via gluconeogenesis

3. Lipid metabolism: GH promotes the release of free fatty acids and glycerol from adipose tissue, increases circulating free fatty acids, causes increased oxidation of free fatty acids in the liver

4. Mineral metabolism: GH promotes a positive calcium, magnesium, and phosphate balance (promotes growth of long bones)

5. Prolactin-like effects

Pathophysiology: dwarfism, gigantism, acromegaly

Prolactin (PRL) peptide for eight hormones

  • is secreted in the adenohypophysis

    Biochemical actions: the initiation and maintenance of lactation

    Pathophysiology: tumors of prolactin-secreting cells cause amenorrhea and galactorrhea in women, gynecomastia and impotence in men

The pituitary and placental glycoproteins: peptide for eight hormones

Thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) a chorionic gonadotropin (CG)

  • structural similarities (common ancestral gene): 2 subunits-α (identical for all of these hormones) and β (determines the specific biologic activity)

  • synthesized as preprohormones and are subject to posttranslational processing (glycosylation)

  • LH and FSH are responsible for gametogenesis and steroidogenesis in the gonads

hCG is synthesized in the syncytiotrophoblast cells of the placenta; increases in blood and urine shortly after implantation; its detection is the basis of many pregnancy tests

hCG- β subunit

Biosynthesis of catecholamines in the adrenal medulla peptide for eight hormones





  • Tyrosine hydroxylase: oxidoreductase, cofactor tetrahydropteridine; inhibition by the catecholamines, tyrosine derivates, and by chelating iron

  • Dopa decarboxylase: cofactor pyridoxal phosphate; inhibitors α-methyldopa

  • Dopamine β-hydroxylase: mixed function oxidase, ascorbate as an electron donor, copper at the active site

  • Phenylethanolamine-N-methyltransferase: the synthesis is induced by glucocorticoid hormones

Catecholamines are rapidly metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)

Different metabolites are formed; two classes have diagnostic significance: metanephrines and 3-methoxy-4-hydroxymandelic acid (vanillylmandelic acid); measurable in urine; elevation in pheochromocytoma

Parathyroid hormone (PTH) catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)








  • PTH affects calcium homeostasis

  • Increases the rate of dissolution of bone, reduces the renal excretion of Ca2+, increases the efficienty of calcium absorption from the intestine by promoting the synthesis of calcitriol

Endoplasmic reticulum

Parathyroid gland

Golgi apparatus

Blood (biological active)


Insulin catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)

  • polypeptide consisting of 2 chains linked by 2 disulfide bridges

  • Synthesis and posttranslational modification of insulin catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)

  • Hydrophobic pre-sequence (signal peptide) is cleaved after transporting to ER

  • Proinsulin is further transported to GA and cleaved by trypsin-like enzymes and carboxypeptidase E

  • Heterodimer and C-peptide are formed

The human insulin gene has been isolated catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)

The synthesis of human insulin in bacterial expression systems, using recombinant DNA technology, affords an excellent source of this hormone for diabetic patients

Diagrammatic structure of the human insulin gene

Areas with diagonal stripes correspond to untranslated regions, open regions correspond to intervening sequences, and stippled regions correspond to coding sequences

  • Inactivation and degradation of peptide hormones catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)

  • Most polypeptide hormones are degraded to amino acids by hydrolysis in the lysosome

  • Certain hormones contain modified amino acids

The hypothalamic releasing hormones

Pyroglutamic acid (pGlu)

C-terminal amino acid amide (Gly-NH2, Ala-NH2, Leu-NH2)






Breakage of the pGlu or cleavage of the C-terminal amide can lead to inactivation of these hormones (this probably accounts for the short half-life of many of these hormones)

Some hormones contain a ring structure joined by a disulfide bridge (oxytocin, vasopressin, somatostatin)

2. Glutathione transhydrogenase



1. Cystine aminopeptidase

Step 1: Breakage of the ring structure

Step 2: Cleavage of cystine

Octapeptide further degradation amino acids

Summary bridge (oxytocin, vasopressin, somatostatin)

  • Peptide hormones are synthetized in the transcription and translation process (DNA-mRNA-peptid) and further modified (posttranslational modification)

  • Peptide hormones interact with specific receptors on the cell surface and trigger a cascade of secondary effects within the cytoplasm (cAMP, second messengers)

  • Peptide hormones form gene families that originate from a common ancestral gene

  • Several important peptide hormones are secreted from the hypothalamus-pituitary cascade (signal amplification, negative feedback interaction)

  • Peptide hormones are produced by many different organs and tissues