VVCllC:I 1eau:,u11-JLIUII wnn a result that the urine

output is around 0.5-1.5 I/day.

Mechanism of action : ADH stimulates

adenylate cyclase causing production of cAMP.

I Water reabsorption is promoted by cAMP.

Inhibitors of adenylate cyclase (e.g. calcium)
inhibit the activity of ADH. This supports the
and
view that ADH action is mostly mediated
are
through cAMP.
land
are Diabetes insipidus : This disorder is charac-
ures terized by the excretion of large volumes of
dilute urine (polyuria). It may be due to
insufficient levels of ADH or a defect in the
receptors of target eel Is.

~nor
1lses
11uli THYROID HORMONES
~inal
Thyroid gland (weighs about 30 g in adults) is
located on either side of the trachea below the
larynx. It produces two principal hormones
the
(Fig.19.9)-thyroxine (T 4 ; 3,5 ,3' ,5' -tetraiodo-
thyron i ne) and 3,5,3'-triiodothyronine (T 3) -
cles)
wh ich regulate the metabolic rate of the body.
Thyroid gland also secretes calcitonin, a hormone
1als, concerned with calcium homeostasis (discussed
elial under calcium metabolism, Chapter 18).
east.
milk Biosynthesis of thyroid hormones
Iodine is essential for the synthesis of thyroid
,ears hormones. More than half of the body's total
iodine content is found in the thyroid gland.
438 BIOCHEMIST RY

I I Thyroglobulin and synthesis of T3 and T4 :

3 Thyroglobulin (mol. wt. 660,000) is a
H0- 0
3' \ - 0 - 0\ -CH2-CH-COOH glycoprotein and precursor for the synthesis of
s· s I
I
- I
- NH 2 T 3 and T4 . Thyroglobulin contains about 140
3, 5, 3', 5'-Tetralodothyronlne (thyroxine, T4 ) tyrosine residues which can serve as substrates
for iodine for the formation of thyroid hormones.

HO
I

\h_J - o-0\I

I
CH2-9H-COOH
NH
2
Tyrosine (of thyroglobulin) is first iodinated at
position 3 to form monoiodotyrosine (MIT) and
then at position 5 to form diiodotyrosine (DIT).
Two molecules of DIT couple to form thyroxine
3,5,3'-Trllodothyronlne (T3) (T4 ). One molecule of MIT, when coupled with

n
one molecule of DIT, triiodothyronine (T 3 ) is
produced. The mechanism of coupling is not
well understood. The details of synthesis of T3
HO- o~ -0
I
- \ _J CH,-rH-COOH
NH
2
and T4 are given under tyrosine metabolism
(Chapter 15). A diagrammatic representation is
3, 3', 5'-Trilodothyronlne (reverse T3, rT~ depicted in Fig.19.10.

Fig. 19.9 : Structures of thyroid hormones As the process of iodination is completed,

(Refer Fig. 15.21 for their biosynthesis).
Uptake of iodide : The uptake of iodide by
the thyroid gland occurs against a concentration
gradient (about 20 : 1). It is an energy requiring
process and is linked to the ATPase dependent
Na•-K+ pump. Iodide uptake is primarily
controlled by TSH. Antithyroid agents such as
thiocyanate and perchlorate inhibit iodide
transport.
each molecule of thyroglobulin contains about
6-8 molecules of thyroxine (T4 ). The ratio of T3
to T4 in thyroglobulin is usually around 1 : 10.
Storage and release of
thyroid hormones
Thyroglobulin containing T4 and T3 can be
stored for several months in the thyroid gland. It
is estimated that the stored thyroid hormones can
meet the body requirement for 1-3 months.

Formation of active iodine : The conversion Thyroglobulin is digested by lysosomal

of iodide U-) to active iodine (I+) is an essential
step for its incorporation into thyroid hormones.
Thyroid is the only tissue that can oxidize 1- to
a higher valence state 1+. This reaction requires
H 202 and is catalysed by the enzyme
thyroperoxidase (mol. wt. 60,000). An NADPH
dependent system supplies H 20 2 .
proteolytic enzymes in the thyroid gland. The
free hormones thyroxine (90%) and
triiodothyronine (10%) are released into the
blood, a process stimulated by TSH. MIT and
DIT produced in the thyroid gland undergo
deiodination by the enzyme deiodinase and the
iodine thus liberated can be reutilized.

✓"
NADP+ NADPH + H+
TSH promotes the oxidation of iodide to
active iodine while the antithyroid drugs
(thiourea, thiouracil, methinazole) inhibit.
Transport of T 4 and T 3
02
Two specific binding proteins-thyroxin e
binding globulin (TBG) and thyroxine binding
prealbumin (TBPA)-are responsible for the
transport of thyroid hormones. Both T4 and T3
are more predominantly bound to TBG. A small
fraction of free hormones are biologically active.
T4 has a half-life of 4-7 days while T3 has about
one day.
Chapter 19 : HORMONES 439

correlated to thyroid hormones and this, in turn,

0
with ATP util ization. Obesity in some individuals
is attributed to a decreased energy utilization and
heat production due to diminished Na+-K+
ATPase activity.

'+i Iodination 2. Effect on protein synthesis : Thyroid

hormones act like steroid hormones in promoting
protein synthesis by acting at the transcriptional
level (activate DNA to produce RNA). Thyroid
MIT
hormones, thus, function as anabolic hormones
Thioperoxldase and cause positive nitrogen balance and promote
growth and development.

,-I 1 Coupling 3. Influence on carbohydrate metabolism :

Thyroid hormones promote intestinal absorption
of glucose and its utilization. These hormones
1
Delodlnatlon increase gluconeogenesis and glycogenolysis,
(delodlnase) with an overall effect of enhancing blood
glucose level (hyperglycemia).
T3 T4 4. Effect on lipid metabolism : Lipid turnover
Proteolysis and utilization are stimulated by thyroid
hormones. Hypothyroidism is associated with
elevated plasma cholesterol levels which can be
reversed by thyroid hormone administration.

To target tissues Regulation of T 3 and T 4 synthesis

Fig. 19.10: Biosynthesis of thyroid hormones-
diagrammatic representation [Note : Refer Fig. 15.21 for
synthesis with structures; Tgb-Thyroglobulin; /+- Active
Iodine; T3- Triiodothyronine; T4- Thyroxine; MIT- Monoi-
odotyrosine; DIT-Diiodotyrosine;
A. As-Amino acids].
Biochemical functions of
thyroid hormones
Triiodothyronine (T3 ) is about four times more
active in its biological functions than thyroxine
(T4 ) . The following are the biochemical functions
attributed to thyroid hormones (T 3 and T4 ).
1 . Influence on the metabolic rate : Thyroid
hormones stimulate the metabolic activities and
increases the oxygen consumption in most of the
tissues of the body (exception-brain , lungs,
testes and retina) .
Na+-K+ ATP pump : This is an energy depen-
dent process which consumes a major share of
cellular ATP . Na+-K+ ATPase activity is directly
The synthesis of thyroid hormones is
controlled by feedback regulation (Fig.19.11). T3
appears to be more actively involved than T4 in
the regulation process. The production of thyroid
stimulating hormone (TSH) by pituitary, and
thyrotropin releasing hormone (TRH) by
hypothalamus are inhibited by T3 and, to a lesser
degree, by T4 . The increased synthesis of TSH
and TRH occurs in response to decreased
circulatory levels of T 3 and T4 . As already
discussed, the body has sufficient stores of
hormones to last for several weeks. Hence it
takes some months to observe thyroid functional
deficiency.
Metabolic fate of T 3 and T 4
Thyroid hormones undergo deiodination in
the peripheral tissues. The iodine liberated may
be reutilized by the thyroid. T 3 and T4 may get
conjugated with glucuronic acid or sulfate in the
liver and excreted through bile. Thyroid
hormones are also subjected to deamination to
440 BIOCHEMIST RY

produce tetraiodothyroacetic acid

(from T4 ) and triiodothyroacetic acid
(from T3) which may then undergo
conjugation and excretion.
TRH
Abnormalities of thyroid
function le
Among the endocrine glands,
thyroid is the most susceptible for
hypo- or hyperfunction.
Three abnormalities associated
with thyroid functions are known.
Goiter : Any abnormal increase
in the size of the thyroid gland is
known as goiter. Enlargement of
thyroid gland is mostly to
compensate the decreased synthesis
of thyroid hormones and is
associated with elevated TSH.
Goiter is primarily due to a failure
in the autoregulation of T3 and T4
synthesis. This may be caused by
deficiency or excess of iodide.
Metabolic Protein carbohydrate Utilization Maintenance
Goitrogenic substances ratet synthesist metabolismt of llpidst of H2O, electrolyte
(goitrogens) These are the balance
substances that interfere with the Fig. 19.11 : Regulation of synthesis and functions of thyroid
production of thyroid hormones. hormones-an overview (TRH-Thyrotropin-stimulating hormone:
These include thiocyanates, nitrates TSH-Thyroid stimulating hormone: T:r Triiodothyronine:
and perchlorates and the drugs such T4-Thyroxine; @ -Promoting effect; 0 -lnhibitory effect).
as thiourea, thiouracil, thiocarbamide
etc. Certain plant foods-cabbage, cauliflower and irritability, anxiety, rapid heart rate, loss of
turnip-contain goitrogenic factors (mostly thio- weight despite increased appetite, weakness,
cyanates). diarrhea, sweating, sensitivity to heat and often
protrusion of eyeballs (exopthalmos).
Simple endemic goiter : This is due to iodine
deficiency in the diet. It is mostly found in the Hyperthyroidism is caused by Grave's disease
geographical regions away from sea coast where (particularly in the developed countries) or due
the water and soil are low in iodine content. to increased intake of thyroid hormones. Grave's
Consumption of iodized salt is advocated to disease is due to elevated thyroid stimulating
overcome the problem of endemic goiter. In /gG also known as long acting thyroid stimulator
certain cases, administration of thyroid hormone (LATS) which activates TSH and, thereby,
is also employed . increases thyroid hormonal production.
Hyperthyroidism : This is also known as Thyrotoxicosis is diagnosed by scanning and/
thyrotoxicosis and is associated with or estimation of T3 , T4 (both elevated) and TSH
overproduction of thyroid hormones. (decreased) in plasma. The treatment includes
Hyperthyroidism is characterized by increased administration of antithyroid drugs. In severe
metabolic rate (higher BMR) nervousness, cases, thyroid gland is surgically removed.
Chapter 19 : HORMONES
Hypothyroidism : This is due to an
impairment in the function of thyroid gland that
often causes decreased circulatory levels of T3
and T4 . Disorders of pituitary or hypothalamus
also contribute to hypothyroidism. Women are
more susceptible than men. Hypothyroidism is
characterized by reduced BMR, slow heart rate,
weight gain, sluggish behaviour, constipation,
sensitivity to cold, dry skin etc.
Hypothyroidism in children is associated with
physical and mental retardation, collectively
known as cretinism. Early diagnosis and proper
treatment are essential. Hypothyroidism in adult
causes myxoedema, characterized by bagginess
under the eyes, puffiness of face, slowness in
physical and mental activities.
Thyroid hormonal administration is employed
to treat hypothyroidism.
Laboratory diagnosis of
thyroid function
Measurement of basal metabolic rate (BMR)
was once used to reflect thyroid activity. The
estimation of serum protein bound iodine (PBI),
representing the circulating thyroid hormones,
was employed for a long time to assess thyroid
function. The normal serum PBI concentration is
3-8 µg/100 ml.
Hypothyroidism is associated with decreased
PBI and hyperthyroidism with increased PBI.
In recent years, more sensitive and reliable
tests have been developed to assess thyroid
activity. The concentration of free T3 and T"'
and TSH are measured (by RIA or ELISA) and
their serum normal concentrations are
Free triiodothyronine (T 3 ) - 80-220 nFfdl
Free thyroxine (T 4 ) 0.8-2.4 nr/dl
Total thyroxine (T 4 ) 5-12 µFfdl
Thyroid stimulating
hormone (TSH)
- <10 µU/ml
Radioactive iodine uptake (RAIU) and
scanning of thyroid gland are also used for
diagnosis.
441
- -1-"<~- Zona glomerulosa
- ~ - Zona fasciculata
'1---+-'t- Zona reticularis
+-t- Medulla
+++-
Fig. 19.12: Adrenal gland with zones (3) and medulla.
Thyroid activity and
serum cholesterol
Serum cholesterol level is increased in
hypothyroidism and decreased in hyperthyroidism.
Unfortunately, cholesterol estimation will be of no
value in the assessment of thyroid function. This is
due to the fact that serum cholesterol level is
elevated in many other disorders (diabetes,
obstructive jaundice, nephrotic syndrome etc.).
However, cholesterol estimation mav be ut;'
for monitoring thyroid
451/809 ••
••
••
i=M;i~MJi+i·)IJ·1dd~tJ•d•j;Jt;,
The adrenal glands are two small organs (each
weighing about 10 g), located above the kidneys.
Each adrenal consists of two distinct tissues-an
outer cortex (with 3 zones) and inner medulla
(Fig.19.12).
As many as 50 steroid hormones (namely
adrenocorticosteroids), produced by adrenal
cortex, have been identified. However, only a
few of them possess biological activity.
Adrenocorticosteroids are classified into three
groups according to their dominant biological
action. However, there is some overlap in their
functions.
1. Glucocorticoids : These are 21-carbon
steroids, produced mostly by zona fasciculata.
They affect glucose (hence the name), amino
acid and fat metabolism in a manner that is
opposite to the action of insulin. Cortisol (also
known as hydrocortisone) is the most important
glucocorticoid in humans. Corticosterone is
predominantly found in rats.
442
2. Mineralocorticoids : These are also 21-
carbon containing steroids produced by zona
glomerulosa. They regulate water and electrolyte
balance. Aldosterone is the most prominent
mineralocorticoid.
3. Androgens and estrogens : The innermost
adrenal cortex zona reticularis produces small
quantities of androgens (19-carbon) and
estrogens (18-carbon). These hormones affecting
sexual development and functions are mostly
produced by gonads. Dehydroepiandro sterone-
a precursor for androgens-is synthesized in
adrenal cortex.
Synthesis of adrenocortico steroids
Cholesterol undergoes cleavage with an
elimination of a 6-carbon fragment to form
pregnenolone. Pregneno/one is the common
precursor for the synthesis of all steroid
hormones.
Conversion of cholesterol to pregnenolone is
catalysed by cytochrome P450 side chain cleavage
enzyme. This reaction is promoted by ACTH.
The enzymes-hydroxylases, dehydrogenases/
isomerases and lyases associated with
mitochondria or endoplasmic reticulum-are
responsible for the synthesis of steroid hormones.
The metabolic pathway for the formation of major
adrenocorticosteroids is given in Fig.19.13.
Biochemical functions of
adrenocortico steroids
1 . Glucocorticoid hormones : The important
glucocorticoids are-cortisol, cortisone and
corticosterone. They bring about several
biochemical functions in the body.
(a) Effects on carbohydrate metabolism
Glucocorticoids promote the synthesis of
glucose (gluconeogenesis). This is brought
about by increasing the substrates
(particularly amino acids) and enhancing
the synthesis of phosphoenolpyruvate
carboxykinase, the rate limiting enzyme
in gluconeogenesis.
The overall influence of glucocorticoids
on carbohydrate metabolism is to increase
BIOCHEMISTR Y
blood glucose concentration. The
biological actions of glucocorticoids
generally oppose that of insulin.
(b) Effects on lipid metabolism : Glucocor-
ticoids increase the circulating free fatty
acids. This is caused by two mechanisms.
(i) Increased breakdown of storage triacyl-
glycerol (lipolysis) in adipose tissue.
(ii) Reduced utilization of plasma free fatty
acids for the synthesis of triacylglyce-
rols.
(c) Effects on protein and nucleic acid
metabolism : Glucocortiocoids exhibit
both catabolic and anabolic effects on
protein and nucleic acid metabolism.
They promote transcription (RNA
synthesis) and protein biosynthesis in
liver. These anabolic effects of
glucocorticoids are caused by the
stimulation of specific genes.
Glucocorticoids (particularly at high
concentration) cause catabolic effects in
extrahepatic tissues (e.g. muscle, adipose
tissue, bone etc.). This results in enhanced
degradation of proteins.
(d) Effects on water and electrolyte meta-
bolism : The influence of glucocorticoids
on water metabolism is mediated through
antidiuretic hormone (ADH). Deficiency
of glucocorticoids causes increased
production of ADH. ADH decreases
glomerular filtration rate causing water
retention in the body.
(e) Effects on the immune system : Gluco-
corticoids (particularly cortisol), in high
doses, suppress the host immune
response. The steroid hormones act at
different levels-damaging lymphocytes,
impairment of antibody synthesis,
suppression of inflammatory response etc.
(f) Other physiological effects of glucocor-
ticoids : Glucocorticoids are involved in
several physiological functions.
(i) Stimulate the fight and flight response
(to face sudden emergencies) of
catecholamines.
444
(ii) Increase the production of gastric HCI
and pepsinogen.
(iii) Inhibit the bone formation, hence the
subjects are at a risk for osteoporosis.
Mechanism of action of glucocorticoids :
Glucocorticoids bind to specific receptors on the
target cells and bring about the action. These
hormones mostly act at the transcription level
and control the protein synthesis.
2. Mineralocorticoid hormones : The most
active and potent mineralocorticoid is
aldosterone. It promotes Na+ reabsorption at the
distal convoluted tubules of kidney. Na+
retention is accompanied by corresponding
4
excretion of K+, H+ and NH ions.
Regulation of aldosterone synthesis : The
production of aldosterone is regulated by
different mechanisms. These include renin-
angiotensin, potassium, sodium and ACTH.
Mechanism of aldosterone action
Aldosterone acts like other steroid hormones. It
binds with specific receptors on the target tissue
and promotes transcription and translation.
Metabolism of adrenocorticosteroids : The
steroid hormones are metabolized in the liver
and excreted in urine as conjugates of
glucuronides or sulfates.
The urine contains mainly two steroids----
17-hydroxysteroids and 17-ketosteroids--derived
from the metabolism of glucocorticoids and
mineralocorticoids. Androgens synthesized
by gonads also contribute to the formation of
17-ketosteroids.
Urinary 17-ketosteroids estimated in the
laboratory are expressed in terms of
dehydroepiandrosterone and their normal
excretion is in the range of 0.2-2.0 mg/day.
Abnormalities of adrenocortical
function
Addison's disease Impairment in
adrenocortical function resu lts in Addison's
disease. This disorder is characterized by
decreased blood glucose level (hypoglycemia),
BIOCHEMISTRY
loss of weight, loss of appetite (anorexia), muscle
weakness, impaired cardiac function, low blood
pressure, decreased Na+ and increased K+ level
in serum, increased susceptibility to stress etc.
Cushing's syndrome : Hyperfunction of
adrenal cortex may be due to long term
pharmacological use of steroids or tumor of
adrenal cortex or tumor of pituitary. Cushing's
syndrome is characterized by hyperglycemia
(due to increased gluconeogenesis), fatigue,
muscle wasting, edema, osteoporosis, negative
nitrogen balance, hypertension, moon-face etc.
Assessment of adrenocortical
function
The adrenocortical function can be assessed
by measuring plasma cortisol (5-15 µg/dl at 9.00
AM), plasma ACTH, urinary 17-ketosteroids etc.
HORMONES OF ADRENAL MEDULLA
Adrenal medulla is an extension of
sympathetic nervous system. It produces two
important hormones-epinephrine (formerly
adrenaline) and norepinephrine (formerly
noradrenaline). Both these hormones are
catecholamines since they are amine derivatives
of catechol nucleus (dihydroxylated phenyl ring).
Epinephrine is a methyl derivative of
norepinephrine. Dopamine is another
catecholamine, produced as an intermediate
during the synthesis of epinephrine.
Norepinephrine and dopamine are important
neurotransmitters in the brain and autonomic
nervous system. The structures of the three
catecholamines are given in Fig.19.14.
Synthesis of catecholamines
The amino acid tyrosine is the precursor for
the synthesis of catecholamines. The pathway is
described under tyrosine metabolism (Chapter
15, Fig.15.2Z,. Catecholamines are produced in
response to fight, fright and flight. These include
the emergencies like shock, cold, fatigue,
emotional conditions like anger etc.
lU U ILI U C:lC:: ;, II I C:lll lU;, . ll ;,11u u1u , II U \ \ C: VC: I, UC:

noted that diabetes insipidus is another

disorder characterized by large volumes of
urine excretion due to antidiuretic hormone
iiM·iNI
Insulin is a polypeptide hormone produced
deficiency). by the {J-cells of islets of Langerhans of
pancreas. It has profound influence on the
Diabetes mellitus is a clinical condition
metabolism of carbohydrate, fat and protein .
characterized by increased blood glucose level
Insulin is considered as anabolic hormone, as it
(hyperglycemia) due to insufficient or inefficient
promotes the synthesis of glycogen,
(incompetent) insulin . In other words, insulin is
triacylglycerols and proteins. This hormone has
either not produced in sufficient quantity or
been implicated in the development of diabetes
inefficient in its action on the target tissues. As a
mellitus.
consequence, the blood glucose level is elevated
which spills over into urine in diabetes mellitus Insulin occupies a special place in the history
(Greek : diabetes-a siphon or running through; of biochemistry as well as medicine. Insu li n was
mellitus-sweet). the first hormone to be isolated, purified and

669

670 BIOCHEMISTRY

synthesized; first hormone to be sequenced; first

hormone to be produced by recombinant DNA
technology.

Structure of insulin
Human insulin (mol. wt. 5,734) contains 51
amino acids, arranged in two polypeptide
chains. The chain A has 21 amino acids while B
has 30 amino acids. Both are held together by
two interchain disulfide bridges, connecting A 7
to 8 7 and A 20 to 8 19 • In addition, there is an Preprolnsulln
intrachain disulfide link in chain A between the

ll1
amino acids 6 and 11 .
Endoplasmic
rettc:uun
Biosynthesis of insulin
Insulin is produced by the ~cells of the islets
of Langerhans of pancreas. The gene for this ~ue~e
protein synthesis is located on chromosome 11 .
The synthesis of insulin involves two precursors,
namely preproinsulin with 108 amino acids s-s
(mol. wt. 11,500) and proinsulin with 86 amino
acids (mol. wt . 9,000). They are sequentially s-s
degraded (Fig.36.1) to form the active hormone
insulin and a connecting peptide (C-peptide) .
Insulin and C-peplide are produced in equimolar
concentration . C-peptide has no biological
activity, however its estimation in the plasma
serves as a useful index for the endogenous
production of insulin .
In the 13-cells, insulin (and also proinsulin)
~WI, Prolnaulln

combines with zinc to form complexes. In this ,~s-s•i-rA

form, insulin is stored in the granules of the
cytosol which is released in response lo various
11s-s II

21
5
20

stimuli (discussed below) by exocylosis. 30 A-chain

8-dlain
Regulation of insulin secretion lnsulln

About 40-50 units of insulin is secreted daily ()-peptide

by human pancreas. The normal insulin concen-
tration in plasma is 20-30 µU/ml. The important
factors that influence the release of insulin from
the ~cells of pancreas are discussed hereunder.
1. Factors stimulating insulin secretion :
These include glucose,
gastrointestinal hormones.
Glucose is the most important stimulus for
insulin release . The effect is more predo-
minant when glucose is administered orally
(either direct or through a carbohydrate-rich
Fig. 31. I : Formation ol insulin from preproinsulin.
meal). A rise in blood glucose level is a signal
for insulin secretion.
am ino acids and Amino acids induce the secretion of insulin.
This is particularly observed after the ingestion
of protein-rich meal that causes transient rise
in plasma amino acid concentration. Among
the amino acids, arginine and leucine are
potent stimulators of insulin release.
674
GLUCAGON
Glucagon, secreted by a-cells of the pancreas,
opposes the actions of insulin. It is a polypeptide
hormone composed of 29 amino acids (mol. wt.
3,500) in a single chain. Glucagon is actually
synthesized as proglucagon (mol. wt. 9,000)
which on sequential degradation releases active
glucagon. Unlike insulin, the amino acid
sequence of glucagon is the same in all
mammalian species (so far studied). Glucagon has
a short half-life in plasma i.e. about 5 minutes.
Regulation of glucagon secretion
The secretion of glucagon is stimulated by
low blood glucose concentration, amino acids
derived from dietary protein and low levels of
ep inephrine. Increased blood glucose level
markedly inhibits glucagon secretion.
Metabolic effects of glucagon
Glucagon influences carbohydrate, lipid and
protein metabolisms. In general, the effects of
this hormone oppose that of insulin.
1 . Effects on carbohydrate metabolism :
Glucagon is the most potent hormone that
enhances the blood glucose level (hyperglycemic).
Primarily, glucagon acts on liver to cause
increased synthesis of glucose (gluconeogenesis)
degradation of glycogen
and enhanced
(glycogenolysis). The actions of glucagon are
mediated through cyclic AMP (Chapter 13) .
2. Effects on lipid metabolism : Glucagon
promotes fatty acid oxidation resulting in
energy production and ketone body synthesis
(ketogenesis) .
3. Effects on protein metabolism : Glucagon
increases the amino acid uptake by liver which,
in turn, promotes gluconeogenesis. Thus,
glucagon lowers plasma amino acids.
Mechanism of action of glucagon
Glucagon binds to the specific receptors on
the plasma membrane and acts through the
mediation of cyclic AMP, the second messenger.
The details are given elsewhere (Chapter 19).
BIOCHEMISTRY
REGULATION OF BLOOD GLUCOSE
LEVEL (HOMEOSTASIS OF
BLOOD GLUCOSE)
Glucose is carbohydrate currency of the
body. An adult human body contains about 18 g
free glucose. This amount is just suffic ient to
meet the basal energy requirements of the body
for one hour! The liver has about 100 g
stored glycogen. Besides this, it is capable of
producing about 125-150 mg glucose/minute or
180-220 g/24 hrs.
Expression of glucose concentration : In most
developed countries, plasma glucose (instead of
blood glucose) is estimated and expressed as SI
units (mmol/I). This is not however so, in
developing countries for practical reasons . II
may be noted that the plasma concentration
of glucose is slightly higher (about 15%)
than blood glucose. Further, a glucose
concentration of 180 mg/di (plasma or blood)
corresponds to 10 mmol/1. In this book,
expression of blood glucose as mg/di is more
frequently used.
A healthy individual is capable of maintaining
the blood glucose concentration within a narrow
range. The fasting blood glucose level in a post-
absorptive state is 70-100 mg/di (plasma glucose
80-120 mg/di). Following the ingestion of a
carbohydrate meal, blood glucose may rise to
120-140 mg/di. The fasting blood glucose value
is comparatively lower in ruminan t an imals
(sheep 30-40 mg/di; cattle 50-60 mg/di), while it
is higher in birds (250-300 mg/di).
The term hyperglycemia refers to an increase
in the blood glucose above the norma l level.
Hypoglycemia represents a decreased blood
glucose concentration . Excretion of glucose in
urine is known as glycosuria. The concentration
of blood glucose is dependent on the quantity of
glucose that enters the circulation from various
sources (dietary carbohydrates, glycogenolysis,
gluconeogenesis etc.) and the amount that is
utilized for different metabolic purposes
(glycolysis, glycogenesis, fat synthesis etc.) as
illustrated in Fig.36.4.