CARBOHYDRATES METABOLISM

PROF.DR. Mursal O. Sheikh

PROF. OF MEDICAL BIOCHEMISTRY
Benadir University
TRICARBOXYLIC ACID CYCLE
( TCA ) OR CITRIC ACID
CYCLE
TCA CYCLE AND PYRUVATE DEHYDROGENASE

 TCA cycle is the final common pathway for complete

oxidation of carbohydrates, lipids and proteins.

 For complete oxidation of pyruvic acid via TCA cycle Pyruvic

acid is firstly converted into acetyl CoA

 Oxidation of Pyruvate to Acetyl CoA catalyzed by

group of enzymes named Pyruvate Dehydrogenase
Complex
Pyruvate enter the mitochondria via a special pyruvate
transporter.
Mitochandrial pyruvate is oxidative decarboxylated to acetyl
CoA in a reaction catalyzed by several enzymes working
sequentially designed as pyruvate dehydrogenase complex
PYRUVATE DEHYDROGENASE COMPLEX:

 It needs coenzymes, vitamin B complex derivatives;

thiamin pyriphosphate ,(TPP , vitamin B1 ), CoASH,
Lipoic acid, NAD.
 It provide 3 ATP via oxidation of NADH.
 It is activated by insulin and
 inactivated by acetyl CoA, ATP and NADH.


Inherited Pyruvate dehydrogenase deficiency or
deficiency of vitamin B1 ( TPP) leads to
accumulation of pyruvic acid and lactic acid leading to
lactic acidosis
 Acidosis : pH of blood less than 7.3
 Normal blood Ph 7.3 – 7.5 (7.4 )
CONVERSION OF PYRUVATE INTO ACETYL COA

CH3 Thiamin diphosphate,

Lipoate-SH
Mg2+
CH3
C=O + + CO2
HS.CoA COS.CoA
COO- NAD+ NADH + H+

Pyruvate Coenzyme A Acetyl Coenzyme A

Cofactors from vitamins and a mineral

 Glucose fatty acids, ketone bodies
glycolysis
Reactions of TCA cycle
PDH
Pyruvate Acetyl CoA CoA

[1
] Citrate
Oxaloacetate
cis- Aconitate
NADH
Isocitrate
[6
NAD+
]
NAD+
[2] NADH, CO2
Malate
-Ketoglutarate
CoA, NAD+
[3
] NADH, CO2
Fumarate [4 Succinyl CoA
[5 ]
FADH2 ]
Succinate GDP AT
FAD GTP P

. ADP
 Energy production from the complete oxidation of
pyruvate:

I. PYRUVATE TO ACETY COA

+3 ATP Pyruvate dehydrogenase (from
NADH)

+3 ATP
II. TCA ENERGY (12Isocitrate
ATP/turndehydrogenase
of TCA cycle) (from NADH)
+3 ATP Ketoglutarate dehydrogenase (from NADH)
+1 ATP Succinyl CoA synthetase (from GTP)
+2 ATP Succinic dehydrogenase (from FADH2)
+3 ATP Malate dehydrogenase (from NADH)

Total : +15 ATP

IMPORTANCE OF
TRICARBOXYLIC ACID
(TCA )CYCLE
 Supply energy; provide 12 ATP / cycle
(3 NADH 9 ATP + 1 FADH2 2 ATP + 1 1
GTP ATP
 Provide
 important
Production of CO2 compounds as:
o Succinyl CoA : is important for synthesis of heme
porphyrine and for ketolysis (breakdown of ketone bodies)
o Citric acid : provide Acetyl CoA extramitochondia that used
for synthesis of fatty acids and cholesterol . Citric acid pass
outside the mitochondria and under effect of enzyme
ATP– Citrate lyase, is splitted into Acetyl CoA and
Oxalacetic.
o Amino acids are derived from α-Ketoacids ;
α-Ketoglutaric (glutamic) and oxalacetic acid (aspartic).
 Inter-conversion between carbohydrates, proteins and
lipids.
TCA cycle important for Inter-conversion
between carbohydrates, proteins and
lipids

Aspartic acid

Glutamic acid

Valine
Isoleucine
methionon
e
FATES OF PYRUVATE:

 Pyruvate  acetyl-CoA
 Occurs in mitochondria
 Produce CO2and NADH + H+
 Catalyzed by Pyruvate Dehydrogenase
 *Acetyl-CoA used in the TCA cycle
 Pyruvate  Lactate
 Produce CO2and NAD+
 Anaerobic glycolysis
 Catalyzed by Lactic dehydrogenase
 Pyruvate  oxalacetic acid
 Accept CO2and consume ATP
 Catalyzed by Pyruvate carboxylase
 Gluconeogenesis pathway
 Reverse of glycolysis
 Pyruvate  amino acid; alanine
Catalyzed by alanine amino transpherase (ALT)
gluconeogenesis GLUCOSE

glycolysis
alanine lactate
PYRUVATE dehydrogenase Lactate
amino-
transferase
Alanine pyruvate pyruvate
carboxylase dehydrogenase

lipogenesis
Oxaloacetate Acetyl CoA Fatty acids
citric acid -oxidation
cycle

ketone cholesterol
CO2 ketogenesis
(liver only) oxidation synthesis

Ketone bodies steroid

Cholesterol hormones
(endocrine glands)

Metabolic sources and fates of pyruvate and acetyl

CoA.
SOURCES AND FATES OF ACETY
COA:
 I - Sources of Acety CoA:
 From glucose by glycolysis and oxidative decarboxylation of
pyruvic acid.
 From fatty acids by ß- oxidation.
 From amino Acids after catbolism of carbon skeleton as:
lysine, leucine , tryptophan , Phenyl alanine and tyrosine.
 Ketolysis of ketone bodies.

 II - Fates of Acety CoA:

 Enters TCA cycle for complete oxidation and production of
energy.
 Synthesis of fatty acid.
 Synthesis of cholesterol and steroid hormones.
 Synthesis of ketone bodies
 ANAPLEROTIC REACTIONS REPLENISH THE
CYCLE INTERMEDIATES

 TCA cycle intermediate concentrations depend on the

activity of ancillary enzymes, which add material to
the cycle from amino acid or carbohydrate sources,
or alternatively remove intermediates for use in
biosynthetic reactions.
 Certain intermediates can be replenished by
anaplerotic reactions
 An important anaplerotic (or "filling up") reaction is
catalysed by pyruvate carboxylase, which forms
oxaloacetate from pyruvate within the mitochondria
and is powerfully activated by acetyl CoA.
 This reaction is quite important in the liver and kidney.
 Pyruvate Carboxylase

An important anaplerotic (or "filling up") reaction is catalysed

by pyruvate carboxylase, which forms oxaloacetate from
pyruvate