Carbohydrates Metabolism Biochemistry for Nurses
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Metabolism of glycogen can be discussed under two headings:
A. Synthetic
phase: Formation of glycogen
B. Catabolic
phase: Breakdown of glycogen
Glycogenesis
Definition:
It is the
formation of glycogen from glucose. Sites: Principally it occurs in liver and
skeletal muscles, but it can occur in every tissue to some extent.
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Stimulation of Glycogenesis |
Inhibition of Glycogenesis |
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1. Insulin: Insulin increases the Protein-phosphatase-1 activity |
1. Increased concentration of glycogen inhibits glycogenesis,
“Feedback” inhib |
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2. Glucocorticoids: Effects seen 2 to 3 hours after
administration. Enhances gluconeogenesis and glycogen synthesis in liver Increases synthesis of the enzyme glycogen synthase |
2. Increased concentration of cyclic-AMP ↑ stimulates inhibitor-1, to form ‘active’ inhibitor-1-P,. which in
turn inhibits Protein Phosphatase-1 |
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3. Glucose: High substrate concentration increases synthesis
(allostery) |
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CLINICAL ASPECTS
Relation of
glycogenesis with K+ influx into the cell:
• Clinical
importance in treatment of hyperkalaemia, when insulin and glucose are
administered.
• Importance in
treatment of diabetic ketoacidosis, with insulin and glucose, danger of
“hypokalaemia” to precipitate. The patient should be monitored for potassium
level in blood while treating diabetic ketoacidosis with insulin and glucose
infusion.
Glycogenolysis
Definition:
Breakdown of
glycogen to glucose is called as glycogenolysis.
Regulation of
Glycogen Metabolism . Regulation of glycogen metabolism is
achieved by a balance in activities between Glycogen synthase and
Phosphorylase, which are as follows:
• Substrate
control (through allostery) as well as
• Hormonal
control and by
• End products.
Hexose Monophosphate (HMP) Shunt
An Alternate
Pathway for Oxidation of Glucose
Synonyms:
Variously called as:
• Hexose
monophosphate pathway or shunt
• Pentose
phosphate pathway (PP-pathway)
• Pentose cycle
•
Phosphogluconate pathway
•
Warburg-Dickens-Lipman Pathway.
Biomedical
Importance
• Though it is
oxidation of glucose, but it is not meant for energy.
• Provides
NADPH which is required for various reductive synthesis in metabolic pathways.
• Provides
pentoses required for nucleic acid synthesis.
• Deficiency of
a particular enzyme leads to haemolytic anaemia, which is of great clinical
importance.
EM and HM Path Way Comparison
|
EM Pathway |
HM Pathway |
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2. Not a multicyclic process |
1. Occurs in certain special tissues for special function |
|
1. Occurs in all tissues |
2. Multicyclic process |
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3. Oxidation by dehydrogenation but NAD is H-acceptor |
3. Oxidation achieved by dehydrogenation but NADP* is used as
H-acceptor |
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4. ATP is required and ATP is produced |
4. Not meant for energy; ATP is not produced, ATP is required for
glucose to glucose-6-P. (for phosphorylation) and for interconversion of
Pentoses |
|
5. CO2 is never formed |
5. CO2 is produced |
Regulation of HMP Shunt
1. Reaction catalysed by G-6-PD, the first reaction of the pathway constitutes the rate-limiting step. It is primarily regulated by cytoplasmic levels of NADP+ and NADPH, thus the ratio of the two, i.e. [NADP+]/ [NADPH]. If the cytoplasmic ratio is high, i.e. a rise in NADP+, enhances the “rate-limiting” reaction as well as the shunt pathway.
A decrease in the ratio, i.e. a rise in NADPH level,
inhibits both G-6-PD and 6-phosphogluconate dehydrogenase by making less NADP+
available for their catalytic reactions and also by competing with NADP+ to
occupy the enzyme binding site of G-6-PD.
2. Activities
of both dehydrogenases and the rate of the pathway are enhanced on feeding high
carbohydrate diets and are reduced in starvation and dibetes mellitus.
3. Increase in
FA synthesis and steroid synthesis re-oxidises NADPH to NADP+ and cytoplasmic
ratio of NADP+/NADPH increased which enhances the shunt pathway.
4. Hormones
• Insulin:
Induces the synthesis of both the dehydrogenases and thus enhances the activity
of the pathway.
• Thyroid
hormones: Enhances the activity of G-6- PD and thus the shunt pathway.
Uronic Acid Pathway
It is an
alternate pathway for oxidation of glucose.
Biomedical
Importance
• In this
pathway energy is not produced.
• Major
function is to produce D-Glucuronic acid which is mainly utilised for
detoxication of foreign chemicals (Xenobiotics). Also used for synthesis of
MPS.
• Inherited
deficiency of an enzyme in this pathway produces ‘essential pentosuria’.
• Total absence
of one particular enzyme in primates, accounts for the fact that ascorbic acid
(vitamin C) cannot be synthesised by humans, and requires to be provided in the
diet.
Gluconeogenesis
Definition:
The formation
of glucose or glycogen from noncarbohydrate sources is called gluconeogenesis.
Biomedical
Importance
Why
Gluconeogenesis is Necessary in the Body?
1.
Gluconeogenesis meets the requirements of glucose in the body when
carbohydrates are not available in sufficient amounts from the diet. Even in
conditions, where fat is utilized for energy still certain basal level of
glucose is required to meet the need for glucose for special uses, e.g.
• Source of
energy for nervous tissues and erythrocytes,
• Required for
maintaining level of intermediates of TCA cycle,
• Source of
glyceride-glycerol-P required for adipose tissue,
• It is a
precursor of milk sugar (lactose) for lactating mammary gland,
• It serves as
only fuel for skeletal muscles in anaerobic conditions.
2.
Gluconeogenic mechanisms are required to clear the products of metabolism of
other tissues from the blood, e.g.
• Lactic acid
produced by muscles and erythrocytes,
• Glycerol which is continuously produced by
adipose tissue by lipolysis of TG (triacyl glycerol).
Hormones in Gluconeogenesis
• Glucagon: It
increases gluconeogenesis from Lactic acid and amino acids.
•
Glucocorticoids: They stimulate gluconeogenesis by increasing protein
catabolism in the peripheral tissues and increasing hepatic uptake of amino
acids and increases activity of transaminases and other enzymes concerned in
gluconeogenesis.
Fates of Lactic Acid In The Body
1.Chief fate is
conversion to Pyruvate and its utilisation as pyruvate which either undergoes
oxidative decarboxylation to form Acetyl-CoA or it can be glucogenic.
2. What is
“Cori Cycle”? Once formed Lactic acid can be further metabolised only by its
reconversion to pyruvate as stated above. In contrast to the phosphorylated
intermediates of glycolysis which are locked in the cells, lactates and
pyruvates can readily diffuse out from the cells in which they are produced and
pass into the circulation.
3.
Lactate-Propanediol Pathway Miller and Olson observed that lactic acid
utilisation by rat ventricle slices in vitro could not be completely inhibited
by sodium fluoride and by anaerobic conditions.
Biosynthesis of Lactose
In synthesis of
Lactose in lactating mammary gland, UDP glucose is converted to UDP-galactose
by the enzyme epimerase. UDP-Galactose condenses with one molecule of glucose
to form Lactose, the reaction is catalysed by the enzyme Lactose synthetase.
Lactose synthetase also called as galactosyl transferase.
Metabolism of Fructose
Dietary Sources
of Fructose: Fructose is present in fruit juices and honey. Chief dietary
source is sucrose, a diasaccharide, taken as table sugar (cane sugar). Sucrose
is hydrolysed in the intestine to one mol. of glucose and one mol. of fructose
by the enzyme Sucrase. Fructose is absorbed by facilitated transport and taken
by portal blood to liver, where it is mostly converted to glucose.
Biomedical Importance
• Fructose is
easily metabolised and a good source of energy.
• Seminal fluid is rich in fructose and spermatozoa utilises fructose for energy.
• Excess
dietary fructose is harmful—leads to increased synthesis of TG.
• In diabetics,
fructose metabolism through ‘sorbitol’ pathway may account for the development
of cataract.
Regulation of Blood Glucose (Homeostasis) Blood glucose level is maintained within physiological limits 60 to 100 mg% (“true” glucose) in fasting state and 100 to 140 mg% following ingestion of a carbohydrate containing meal, by a balance between two sets of factors:
(A) Rate of
glucose entrance into the blood stream
(B) Rate of its
removal from the blood stream.
Hormonal Influences: (Endocrine Influences) On Carbohydrate Metabolism
Endocrine
organs play an important key role in this homeostatic mechanism.
1.Insulin
2. Adrenocortical
hormones:
3. Anterior
Pituitary Gland
4. Catecholamines
5.Glucagon
6.Thyroid
Hormones
Give your opinion if have any.