Carbohydrates Metabolism Biochemistry for Nurses

Fate of pyruvic
acid depends on the redox state of the tissues:

• In Presence
of O2: Pyruvic acid is oxidatively decarboxylated to two-carbon unit
“Acetyl-CoA”

• In absence of
O2: Pyruvic acid is converted to Lactic acid (LA)

Energetics

    One molecule of
glucose produces two molecules of PA which in turn by oxidative decarboxylation
produces 2 molecules of Acetyl-CoA and 2 NADH. Two molecules of NADH will be
oxidized to 2 molecules of NAD+ producing 6 ATP molecules in respiratory chain.
+ 6 A T P

Citric Acid
Cycle Synonyms:
TCA cycle
(tricarboxylic acid cycle), Krebs’ cycle, Krebs’ citric acid cycle.
Biomedical Importance Of Citric Acid Cycle

• Final common
pathway for carbohydrates, proteins and fats, through formation of 2-carbon
unit acetyl-CoA.

• Acetyl-CoA is
oxidised to CO2 and H2O giving out energy (III pase of catabolism)-catabolic
role.

• Intermediates
of TCA cycle play a major role in synthesis also like heme formation, formation
of non-essential amino acids, FA synthesis, cholesterol and steroid
synthesisanabolic role.

Role Of
Vitamins In Tca Cycle

Five B vitamins
are associated with TCA cycle essential for yielding energy.

• Riboflavin:
In the form of flavin adenine dinuleotide (FAD)— a cofactor for succinate
dehydrogenase enzyme.

• Niacin: In
the form of nicotinamide adenine dinucleotide (NAD) the electron acceptor for
isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and malate
dehydrogenase.

• Thiamine: As
“thiamine diphosphate”—required as coenzyme for decarboxylation in the
α-ketoglutarate dehydrogenase reaction.

• Lipoic acid:
It is required as coenzyme for α-ketoglutarate dehydrogenase reaction.

• Pantothenic
acid: As part of coenzyme A, the cofactor attached to “active” carboxylic acid
residues such as acety CoA and succinyl-CoA

TCA cycle has
dual role

• catabolic,

• anabolic.

(a) Catabolic
role: The two carbon compound acetyl-CoA
produced from metabolism of carbohydrates, Lipids and Proteins are oxidised in
this cycle to produce CO2, H2O and energy as ATP.

(b) Anabolic or
synthetic role:Intermediates of TCA cycle are
utilised for synthesis of various compounds.

Transamination:
Synthesis of non-essential amino acids

Formation of
glucose: (Gluconeogenesis)

Fatty acid
synthesis

Synthesis of
cholesterol and steroids

Haem synthesis

Formation of
acetoacetyl-CoA

Regulation of
TCA Cycle

1. As the
primary function of TCA cycle is to provide energy, respiratory control via the
ETC and oxidative phosphorylation exerts the main control.

2. In addition
to this overall and coarse control, several enzymes of TCA cycle are also
important in the regulation.

Shuttle Systems

    NADH produced
in the glycolysis is extramitochondrial, whereas the electron transport chain,
where NADH has to be oxidised to NAD+ is in the mitochondrion. NADH is not
permeable to mitochondrial membrane. 

    It is envisaged that NADH produced in
cytosol transfer the reducing equivalents through the mitochondrial membrane
via substrate pairs, linked by suitable dehydrogenases by shuttle systems. It
is important that the specific dehydrogenases which act as “shuttle” be present
on both sides of mitochondrial membrane. Two such shuttle systems are there:

1.
Glycerophosphate shuttle

2. Malate
shuttle

Metabolism Of
Glycogen

    Glycogen is the
storage form of glucose, which is stored in animal body specially in liver and
muscles. It is mobilised as glucose whenever body tissues require. Students
should revise their knowledge regarding chemistry of glycogen. Why body stores
glucose as glycogen and not as glucose itself?

Possible
Reasons

1. Being
insoluble it exerts no osmotic pressure, and so does not disturb the
intracellular fluid content and does not diffuse from its storage sites.

2. It has a
higher energy level than a corresponding weight of glucose (though energy has to
be expended to make it from glucose). 3. It is readily broken down under the
influence of hormones and enzyme:

• Into glucose
in liver (to maintain blood glucose level).

• Into lower
intermediates in skeletal muscle and other tissues for energy.

Role of Liver
Glycogen

• It is the
only immediately available reserve store of blood glucose.

• A high liver
glycogen level protects the liver cells against the harmful effects of many
poisons and chemicals, e.g. CCl4, ethyl alcohol, arsenic, various bacterial
toxins.

• Certain forms
of detoxication, e.g. conjugation with glucuronic acid; and acetylation
reactions, are directly influenced by the liver glycogen level.

•.The rate of
deamination of amino acids in the liver is depressed as the glycogen level
rises, so that amino acids are preserved longer in that form and so remain
available for protein synthesis in the tissues.

• Similarly, a
high level of liver glycogen depresses the rate of ketone bodies formation.

Biomedical
Importance

• Liver
glycogen is largely concerned with storage and supply of glucose-1-P, which is
converted to glucose, for maintenance of blood glucose, particularly in between
meals.

• Muscle
glycogen on the other hand, is to act as readily available source of
intermediates of glycolysis for provision of energy within the muscle itself.
Muscle glycogen cannot directly contribute to blood glucose level.

• Inherited
deficiency of enzymes in the pathway of glycogen metabolism produces certain
inherited disorders called as Glycogen storage diseases (GSDs).