This document provides an overview of carbohydrate metabolism. It begins with definitions and classifications of carbohydrates. It then discusses the bonds in carbohydrates and various pathways of carbohydrate metabolism including glycolysis, the Cori cycle, the Krebs cycle, gluconeogenesis, glycogen metabolism, and the hexose monophosphate shunt pathway. It provides details on the key enzymes and reactions involved in each pathway as well as the energy yield and clinical significance.
3. • Carbohydrate as is suggestive by the name are primarily
composed of the elements carbon, hydrogen and oxygen
• Some carbohydrates posses the empirical formula as (C.H₂0)n
where n<=3 satisfying that these carbohydrates are in fact
HYDRATES OF CARBON
• However there are several non-carbohydrate compounds which
also appear as hydrates of carbon eg: acetic acid(C₂H₄O₂) and
lactic acid(C₃H₆O₃)
• Further some of the genuine carbohydrates (eg. Ramnohexose,
C₆H₁₂O₅; Deoxyribose, C₅H₁₀O₄)do not satisfy the general formula
• Hence carbohydrates cannot be always considered as hydrates of
carbon
INTRODUCTION
4. DEFINITION
• Carbohydrates may be defined as
polyhydroxyaldehydes or ketones or compounds
which produce them on hydrolysis.
• The term sugar is applied to carbohydrates soluble in
water and sweet to taste
5. GENERAL USES OF
CARBOHYDRATE
• They are the most abundant source of energy for all organisms (4
Cal/gm)
• Carbohydrates are precursors for organic compounds like fats and
amino acids
• Carbohydrates like glycoproteins and glycolipids participate in cell
growth, adhesion and fertilization
• They are the structural components of plants(cellulose),
exoskeleton of some insects and cell wall of microorganisms
• Carbohydrates also serve as the storage form of energy (glycogen)
to meet the immediate energy demands of the body
20. ENTRY OF GLUCOSE INTO CELLS
• Glucose concentration is very low in cells as
compared to plasma and it does not enter cells
by simple diffusion
• Two specific transport systems are used to
transport glucose into cells and these are
1.Insulin independent transport system of glucose
2.Insulin dependent transport system of glucose
25. Salient features:
25
1) Takes place in all cells of the body.
2) Enzymes present in “cytosomal fraction” of the cell.
3) Lactate – end product – anaerobic condition.
4) Pyruvate(finally oxidized to CO2 & H2O) – end
product of aerobic condition.
5) Tissues lacking mitochondria – major pathway –ATP
synthesis.
6) Very essential for brain – dependent on glucose for
energy.
7) Central metabolic pathway
8) Reversal of glycolysis – results in gluconeogenesis.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36. Energy
Investment
Phase
• Glucose is phosphorylated to glucose-6-phosphate by hexokinase (or)glucokinase.
• Glucose-6-phosphate undergoes isomerization to give fructose -6- phosphate in the presenseof
phospho-hexose isomerase and Mg2+
• Fructose-6-phosphate is phoshorylated to fructose 1,6-bisphosphate by phosphofructokinase.
Splitting
Phase
• Fructose 1,6-bisphosphate glyceraldehyde 3-phosphate + dihydroxyacetone
phosphate.(aldolase enzyme)
• 2 molecules of glyceraldehyde 3-phosphate are obtained from 1 molecule of glucose
Energy
Generation
Phase
• Glyceraldehyde 3-phosphate 1,3-bisphosphoglycerate(glyceraldehyde 3-phosphate dehydrogenase
• 1,3-bisphosphoglycerate 3-phosphoglycerate (phosphoglyceratekinase)
• 3-phosphoglycerate 2-phosphoglycerate (phosphoglycerate mutase)
36
• 2-phosphoglycerate phosphoenol pyruvate (enolase + Mg2+ &Mn2+)
• Phosphoenol pyruvate pyruvate [enol] (pyruvate kinase ) pyruvate [keto] L-Lactate
(lactate dehydrogenase)
39. Energy productionion of glycolysis:
ATPproduction = ATPproduced - ATPutilized
ATPproduced ATPutilized Net energy
In absence of oxygen
(anaerobic glycolysis)
4ATP
(Substrate level
phosphorylation)
2ATP from 1,3 BPG.
2ATP fromphosphoenol
pyruvate
2ATP
From glucose to glucose -
6-p.
From fructose -6-p to
fructose 1,6 p.
2ATP
In presence of oxygen
(aerobic glycolysis)
4ATP
(substrate level
phosphorylation)
2ATP from 1,3 BPG.
2ATP from phosphoenol
pyruvate.
2ATP
-From glucose to glucose-
6-p.
From fructose -6-p to
fructose 1,6 p.
8 ATP/
6 ATP(Pyruvate
dehydrogenase
2NADH,ETC,
Oxidative
phosphorylation)
+ 4ATP or6ATP
(from oxidation of2
NADH + H in
mitochondria).
44. CLINICAL ASPECT
1) Lactic acidosis
- Normal value – 4 to 15 mg/dl.
- Mild forms – strenous exercise, shock, respiratory
diseases
- Severe forms – Impairment/collapse of circulatory
system – myocardial infarction, pulmonary embolism,
uncontrolled hemmorrhage and severe shock.
- The term oxygen debt is used to refer to the excess
amount of O₂ required for the patient to recover
45. 2) Cancer and glycolysis :
- Cancer cells – increased uptake of glucose and
glycolysis.
- Blood vessels unable to supply adequate oxygen –
HYPOXIC condition – Anaerobic glycolysis /
hypoxic glycolysis – Involvement of Hypoxic
inducible transcription factor (HIF).
- Treatment : Cancer cells cannot grow and survive
without proper vascularization hence use drugs that
inhibit vascularization of tumours
47. IRREVERSIBLE STEPS IN
GLYCOLYSIS
• PFK is an allosteric enzyme regulated by allosteric effectors
• ATP, citrate and H+ ions(low pH) are the most important
allosteric inhibitors
49. PASTEUR EFFECT
• The inhibition of glycolysis by oxygen
is known as pasteur effect
• It was discovered by Louis Pasteur
when he observed that anaerobic
yeast culture when left in air reduces
glucose utilization by 7 fold
• In aerobic conditions the levels of
glycolytic intermediates decreases
from fructose-1,6-bisphosphate to
pyruvate
• This is due to the formation of citrates
and ATP by kreb’s cycle which are
allosteric inhibitors of PFK
50. CRABTREE EFFECT
• Basically this is just the opposite of pasteur
effect
• The oxygen consumption by the cell decreases
when more and more amount of glucose is
added to the cell leading to increased amount of
glycolysis
• The rate of glycolysis is inversely proportional to
the oxygen consumption by the cells
52. SIGNIFICANCE OF 2,3-BPG
• It combines with hemoglobin and reduces the
affinity of hemoglobin to RBCs therefore
increasing the unloading of oxygen from
oxyhemoglobin
• Increase of erythrocyte 2,3-bpg is observed in
high altitudes, fetal tissues, anemic conditions
• In all these cases 2,3-bpg will enhance the supply
of oxygen to the tissues
53. CONVERSION OF PYRUVATE TO
ACETYL CoA
• Pyruvate is converted to acetyl CoA
by oxidative decarboxylation
• An irreversible reaction catalyzed
by a multi enzyme complex
(pyruvate dehydrogenase
complex) which is found only in the
mitochondria
• The enzyme PDH requires 5 co-
factors namely-
TPP,lipoamide,FAD,coenzyme A
and NAD+
54. BIOCHEMICAL IMPORTANCE OF PDH
• Lack of Thiamine Pyrophosphate(TPP) inhibits PDH
activity resulting in the accumulation of pyruvate
• In the thiamine deficient alcoholics, pyruvate is
rapidly converted into lactate resulting into lactic
acidosis
• In patients with inherited deficiency of PDH, lactic
acidosis is observed
• PDH can be inhibited by arsenic and mercuric ions
55. CITRIC ACID
CYCLE
KREBS CYCLE /
TRICARBOXYLIC ACID/
TCA CYCLE
Essentially involves the oxidation of acetyl CoA
to CO2 and H2O.
This Cycle utilizes about two-third of total
oxygen consumed by the body.
55
56. BRIEF HISTORY
• It was proposed by Hans Adolf Kreb in 1937
based on the studies of oxygen consumption in
pigeon breast muscle
• He received the Nobel Prize in 1953 for this
discovery
• The original manuscript of TCA cycle was
rejected by the journal ‘Nature’
• He published it in another journal Enzymoligia
• Hans carried the rejection letter (of Nature) with
him and advised the researchers never to be
discouraged by research paper rejection
57. Location of
TCA
• Mitochondrial
matrix
• In close
proximity to
the electronic
transport
chain.
Overview
• 65-70% of the
ATPis
synthesized
• Name : TCA
used because
at the outset
of the cycle
tricarboxylic
acids
participate.
79. • TCA cycle is strictly aerobic in contrast to glycolysis.
• Total of 12 ATPare produced from one acetyl CoA:-
During the process of oxidation of acetyl CoA via citric
acid cycle 3 NADH & 1 FADH2.
Oxidation of 3 NADH by electron transport chain
coupled with oxidative phosphorylation results in 9
ATP,FADH2 2 ATP.
One substrate level phosphorylation.
79
83. REFERENCE
S
1) Biochemistry – U.Satyanarayana-3rd Ed.
2) Textbook of Biochemistry- D.M.Vasudevan -14th
Ed.
3) Textbook of Medical Biochemistry –
M.N.Chattergy – 17th Ed.
4) Text book of Physiology –Ganong – 24th Ed.
5) Text book of Oral Pathology – Shafers- 7th Ed.
6) Principles & practice of Medicine-Davidson –
21st Ed.
83
102. THE CORI CYCLE
The cycle involved in the
synthesis of glucose in liver
from the skeletal muscle lactate
and the reuse of glucose thus
synthesized by the muscle for
energy purpose is known as cori
cycle
130. TYPE ENZYME DEFECT CLINICALFEATURES
Type I (Von Gierke’s
disease)
Glucose-6-
phosphatase
deficiency.
Hypoglycemia, enlarged liver and kidneys,
gastro-intestinal symptoms, Nose bleed, short
stature, gout
Type II (Pompe’s
disease)
Acid maltase
deficiency
Diminished muscle tone, heart failure, enlarged
tongue
Type III (Cori’s
disease,Forbe disease)
Debranching enzyme
deficiency
Hypoglycemia, enlarged liver, cirrhosis, muscle
weakness, cardiac involvement
Type IV (Andersen’s
disease)
Branching enzyme
deficiency
Enlarged liver & spleen, cirrhosis, diminished
muscle tone, possible nervous system
involvement
Type V (Mcardle’s
disease)
Muscle phosphorylase
deficiency
Muscle weakness, fatigue and muscle cramps
Glycogen storage diseases
13
0
131. TYPE
13
1
ENZYME DEFECT CLINICALFEATURES
Type VI (Her’s
disease)
Liver phosphorylase
deficiency
Mild hypoglycemia, enlarged liver, short
stature in childhood
Type VII (Tarui’s
disease)
Phosphofructokinase
deficiency
Muscle pain, weakness and decreased
endurance
TypeVIII Liver phosphorylase
kinase
Mild hypoglycemia, enlarged liver, short
stature in childhood, possible muscle weakness
and cramps
Type 0 Liver glycogen
synthetase
Hypoglycemia, possible liver enlargement
141. • Pentose or its derivatives are useful for the
synthesis of nucleic acids and nucleotides.
• NADPH is required :
-For reductive biosynthesis of fatty acids and
steroids.
- For the synthesis of certain amino acids.
- Anti-oxidant reaction
- Hydroxylation reaction– detoxification of drugs.
- Phagocytosis
- Preserve the integrity of RBC membrane. 14
1
Significance of HMP Shunt
145. Role of carbohydrates in dental
caries
• Fermentable carbohydrates causes loss of
caries resistance.
• Caries process is an interplay between oral
bacteria, local carbohydrates & tooth surface
Bacteria + Sugars+ Teeth Organic acids
Caries
14
5
146. DENTAL CARIES CAN OCCUR DUE TO INTAKE OF FERMENTABLE CARBOHYDRATES LIKE
SUCROSE
147.
148.
149.
150. Role of carbohydrates in
periodontal disease
Abnormal
glucose metabolism
Diabetes Mellitus
Periodontal disease
Excessive carbohydrate
intake
Obesity
Periodontal disease
15
0
151. CONCLUSION
• Carbohydrate are the most common source of
energy for the living cells. Glucose is the
central molecule in carbohydrate metabolism,
actively participating in a number of
metabolic pathway.
• One component of etiology of dental caries is
carbohydrate which act as substrate for
bacteria. Every effort should be made to
reduce sugar intake for healthy tooth.
15
1
152. REFERENCE
S
1) Biochemistry – U.Satyanarayana-3rd Ed.
2) Textbook of Biochemistry- D.M.Vasudevan -14th
Ed.
3) Textbook of Medical Biochemistry –
M.N.Chattergy – 17th Ed.
4) Text book of Physiology –Ganong – 24th Ed.
5) Text book of Oral Pathology – Shafers- 7th Ed.
6) Principles & practice of Medicine-Davidson –
21st Ed.
15
2