carbohydrate metabolism new

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Presented by:
Keshab Raj Joshi
Lumbini medical college
Pravas, Tansen, Palpa
CARBOHYDRATE METABOLISM

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Major pathway for Carbohydrate metabolism:
1) Glycolysis
2) TCA cycle
3) Gluconeogenesis
4) Glycogenesis
5) Glycogenolysis
6) Hexose monophosphate pathway

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Major pathway for Carbohydrate metabolism:
1) Glycolysis:-
 Glycolysis is defined as the sequence of reaction converting
glucose to pyruvate under aerobic condition and lactate under
anaerobic condition with the production of ATP.
2) TCA Cycle:
 The oxidation of acetyl Co-A to Co2.
 Kreb’s cycle is the final oxidative pathway for carbohydrate, fat,
or amino acids through acetyl Co-A.

4. 3) Gluconeogenesis:
 The synthesis of glucose from non-carbohydrate precursor.
eg: amino acids, glycerol
4) Glycogenesis:
> The formation of glycogen from glucose
4

5.  Metabolism is all the chemical reactions that occur in an
organism
 Cellular metabolism
 Cells break down excess carbohydrates first, then lipids, finally
amino acids if energy needs are not metabolized by
carbohydrates and fat
 Nutrients not used for energy are used to build up structure, are
stored, or they are excreted
 40% of the energy released in catabolism is captured in ATP,
the rest is released as heat
Metabolism

6.  Performance of structural maintenance and
repairs
 Support of growth
 Production of secretions
 Building of nutrient reserves
Anabolism

7.  Breakdown of nutrients to provide energy (in
the form of ATP) for body processes
 Nutrients directly absorbed
 Stored nutrients
Catabolism

8.  Cells provide small organic molecules to
mitochondria
 Mitochondria produce ATP used to
perform cellular functions
Cells and Mitochondria

9. Carbohydrate Metabolism
 Primarily glucose
 Fructose and galactose enter the pathways at various
points
 All cells can utilize glucose for energy production
 Glucose uptake from blood to cells usually mediated by
insulin and transporters
 Liver is central site for carbohydrate metabolism
 Glucose uptake independent of insulin
 The only exporter of glucose

10. Fates of Glucose
 Fed state
 Storage as glycogen
 Liver
 Skeletal muscle
 Storage as lipids
 Adipose tissue
 Fasted state
 Metabolized for energy
 New glucose synthesized

11. High Blood Glucose
Glucose absorbed
Insulin
Pancreas
Muscle
Adipose
Cells
Glycogen
Glucose absorbed
Glucose absorbed
immediately after eating a meal…

12. Glucose Metabolism
 Four major metabolic pathways
 Energy status (ATP) of body regulates which
pathway gets energy
 Immediate source of energy
 Pentophosphate pathway
 Glycogen synthesis in liver/muscle

13. Fate of Absorbed Glucose
 1st Priority: glycogen storage
 Stored in muscle and liver
 2nd Priority: provide energy
 Oxidized to ATP
 3rd Priority: stored as fat
 Only excess glucose
 Stored as triglycerides in adipose

14. GLYCOLISIS
 Glycolysis oxidation of glucose energy
 It can function either aerobically or anaerobically
pyruvate lactate
 Occurs in the cytosol of all cell
 AEROBICALLY GLYCOLYSIS :
Pyruvate Mitochondria oxidized to Acetyl
CoA Kreb’s Cycle
CO2 + H2O + ATP

15. Glucose Utilization
Glucose
Pyruvate
Ribose-5-phosphate
Glycogen
Energy
Stores
Pentose
Phosphate
Pathway
Glycolysis
Adipose

16. Glucose Utilization
Glucose
Pyruvate
Ribose-5-phosphate
Glycogen
Energy
Stores
Pentose
Phosphate
Pathway
Glycolysis
Adipose

17. Glycolysis
 Sequence of reactions that converts glucose into
pyruvate
 Relatively small amount of energy produced
 Glycolysis reactions occur in cytoplasm
 Does not require oxygen
Glucose → 2 Pyruvate
Lactate (anaerobic)
Acetyl-CoA (TCA cycle)

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Major pathway for Carbohydrate metabolism:
1) Glycolysis:-
 Also called as embden-meyerhof pathway( E.M pathway)
Defination:
Glycolysis is defined as the sequence of reaction converting
glucose to pyruvate under aerobic condition and lactate under
anaerobic condition with the production of ATP.
 Location:
site: liver, cornea of eye, RBC’s, striated muscle.
Subcellular site: cytoplasm.

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FEATURE OF GLYCOLYSIS:
Glycolysis takes place in all cells of body.
Glycolysis occurs in aerobic as well as anaerobic
condition.
It is emergency energy-yielding pathway for cells
in absence of oxygen.
Glycolysis is a major pathway for ATP synthesis in
tissue lacking mitochondria.
eg: RBC, Cornea, lens etc

20. Glycolysis
Glucose + 2 ADP + 2 Pi
2 Pyruvate + 2 ATP + 2 H2O

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Production of ATP in glycolysis:
Enzyme reaction ATP
generated used
1) hexokinase G- G-6-p 1
2) Phosphofructokinase Fructose-6-p--> 1
Fructose 1,6 biphosphate
3) Glyceraldehyde-3-P DH glyceraldehyde-3-P 2x3=6
1,3-biphosphoglycerate

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Production of ATP in glycolysis:
Enzyme reaction ATP
generated used
4) Phosphoglycerate 1,3-biphosphoglycerate- 1x2 = 2
kinase 3-phosphoglycerate
5) Pyruvate kinase phosphoenol pyruvate- 1x2 = 2
pyruvate
Total energy 10 2
So, the total no. of ATP generated in glycolysis is 8.

23. Pyruvate Metabolism
 Three fates of pyruvate:
 Conversion to lactate (anaerobic)
 Conversion to alanine (amino acid)
 Entry into the TCA cycle via pyruvate
dehydrogenase pathway (create ATP)

24. Anaerobic Metabolism of Pyruvate
 Solution:
 Turn NADH back to NAD+ by making lactate (lactic acid)
COO–
C O
CH3
COO–
HC OH
CH3
Lactate
Pyruvate
Lactate dehydrogenase
NADH + H+
NAD+
(oxidized) (reduced)
(oxidized
(reduced

25. Anaerobic Metabolism of Pyruvate:
 ATP yield
 Two ATPs (net) are produced in the
anaerobic breakdown of one glucose
 The 2 NADHs are used to reduce 2 pyruvate
to 2 lactate
 Reaction is fast and doesn’t require oxygen

26. Pyruvate Metabolism -
Anaerobic
Pyruvate Lactate
NADH NAD+
Lactate Dehydrogenase
 Lactate can be transported by blood to liver and
used in gluconeogenesis

27. Cori Cycle
Lactate is converted to pyruvate
in the liver

28. TCA Cycle
 In aerobic conditions TCA cycle links pyruvate to
oxidative phosphorylation
 Occurs in mitochondria
 Generates 90% of energy released from feed
 Oxidize acetyl-CoA to CO2 and capture potential
energy as NADH (or FADH2) and some ATP
 Metabolizes carbohydrate, protein, and fat

29. TCA Cycle
The Citric acid cycle is the most important
metabolic pathway for the energy supply to the body.
About 65-70% of the ATP is synthesized from kreb
cycle.
This cell utilized about 2/3rd of total oxygen
consumed.

30. function of TCA Cycle
It is the final oxidative pathway that oxidises acetyl
Co-A to CO2.
It is the sources of reduced co-enzymes that
provides the substrate for respiratory chain.
It has both anabolic and catabolic role ( Amphibolic
role)
It provides the precursor for the synthesis of Amino
acids and Nucleotides

32. Energetics:-
Enzyme reaction ATP
generated used
1) Isocitrate DH Isocitrate Alfa-KG 3x2=6
2) Alfa-KG DH alfa-KG Succinyl Co-A 3x2=6
3) Succinate Thiokinase Succinyl CoA-Succinate 1x2=2
4) Succinate DH Succinate- Fumarate 2x2=4
5) MDH Malate - oxaloacetate 3x2=6
Total 24 ATP/cycle.

33. Significance of TCA cycle:
1) Common oxidation of acetyl Co-A.
2) ATP generation
3) Final common oxidative pathway.
4) Amphibolic pathway
5) Integration of major metabolic pathways.
6) Many amino acids after transamination enter the TCA
cycle.
Eg: Glutamic acids -------------- Alfa-KG
Aspartate -------------------- oxaloacetate

34. Regulatory enzyme of TCA cycle
1) Citrate Synthase:-
 It is inhibited by ATP, NADH, Acyl CoA and Succinyl CoA.
2) Iso-citrate Dehydrogenase:-
 It is activated by ADP and Inhibited by ATP and NADH
3) Alfa-keto glutarate dehydrogenase:-
 It is inhibited by Succinyl coA and NADH.
4) Availability of ADP:-
 It is very imp. For the TCA cycle to proceed.
 If ADP are unsufficient than oxidation of NADH and
FADH2 through ETC stops.
 Than accumulation of NADH and FADH2 lead inhibition
of enzyme.
 Also need to supply the NAD and FAD essential for TCA
cycle to proceeds. 34

35. Gluconeogenesis:-
Gluco = Glucose
Neo =New
Genesis = synthesis
Defination:
The process by which the glucose molecule are
synthesized from non-carbohydrate precursors/
compounds is called Gluconeogenesis.
The major precursor are:
a) Lactate b) Pyruvate c) Glycerol
d) Glucogenic amino acids. 35

36. a) Alanine, serine, Cysteine, Glycine, threonine, and
tryptophan.
Pyruvate
b) Aspartate and Aspargine
Oxaloacetate
c) Arginine, Glutamate, Glutamine, Histidine,Proline
Alfa-Ketoglutarate 36

37. d) Isoleucine, Methionine,Valine
Succinyl Co-A
e) Phenyl alanine, Tyrosine
Fumarate
37

38. Location:
Sites:
a) Liver ( 60-70%)
b) Renal Cortex
Subcellular site:
a) Cytoplasm
b) Mitochondria
c) Smooth endoplasmic reticulum
38

39. GLUCONEOGENESIS
Pathways that responsible for converting
noncarbohydrate precursors to glucose or glycogen
In mammals occurs in liver and kidney
Major substrate :
1. Lactic acid from muscle, erythrocyte
2. Glycerol from TG hydrolysis
3.Glucogenic amino acid
4. Propionic acid in ruminant

40. Why do we produce glucose?
 Need to maintain glucose levels
within a narrow range in blood.
 Brain, erythrocytes, and muscles in
exertion use glucose at a rapid rate
and require glucose between meals,
especially after several hours.

41.  What is the major precursor?
The major precursor for glucose
biosynthesis is pyruvate.

42. Gluconeogenesis meets the needs of the body for glucose when
carbohydrate is not available from the diet or from glycogenolysis
A supply of glucose is necessary especially for nervous system
and erythrocytes.
The key enzymes are :
1. Pyruvate carboxylase
2. Phosphoenolpyruvate Carboxikinase
3. Fructose 1,6-biphosphatase
4. Glucose-6-phosphatase

43. Glyceraldehyde-3-phosphate
Dehydrogenase
Phosphoglycerate Kinase
Enolase
PEP Carboxykinase
glyceraldehyde-3-phosphate
NAD+
+ Pi
NADH + H+
1,3-bisphosphoglycerate
ADP
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate
H2O
phosphoenolpyruvate
CO2 + GDP
GTP
oxaloacetate
Pi + ADP
HCO3

+ ATP
pyruvate
Pyruvate Carboxylase
Gluconeogenesis
Summary of
Gluconeogenesi
s Pathway:
Gluconeogenesi
s enzyme names
in red.
Glycolysis
enzyme names
in blue.

44. Glucose-6-phosphatase
Fructose-1,6-bisphosphatase
glucose Gluconeogenesis
Pi
H2O
glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
Pi
H2O
fructose-1,6-bisphosphate
Aldolase
glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate
Isomerase
(continued)

45. GLUCONEOGENESIS

46. GLUCONEOGENESIS FROM AMINO ACID

47. CORI CYCLE

48. Cori cycle

49. Importance of Gluconeogenesis:
During starvation gluconeogenesis maintain the blood glucose
level.
The stored glycogen is depleted within the first 12-18hrs of
fasting.
On prolonged starvation the gluconeogenesis is speeded up
and protein catabolism provide the substrate namely
glucogenic amino acids.
Brain alone require 120gm/day of glucose out of 160 gm/day
needed by the entire body so during starvation,
gluconeogenesis is reponsible for providing glucose to brain.
49

50. REGULATION OF GLUCONEOGENESIS:
Gluconeogenesis and Glycolysis are reciprocally regulated so
that one pathway is relatively inactive when the other is active.
Gluconeogenesis occurs during fasting, also stumulated during
prolonged exercise and high protein intake and under
condition of stress:
a) Availability of substrate:
Gluconeogenesis is stimulated by the flow of it’s major
substrate from the peripheral tissue to the liver.
i) Lactate: - elevated during exercise
ii) Amino acids:- elevated when insulin is low and cortisol is
elevated also elevated when protein intake is high. 50

51. REGULATION OF GLUCONEOGENESIS:
b) Hormonal:
Starvation------- Hypoglycemia--------increased Glycogen
Stimulated
Gluconeogenesis
c) Covalent modification of pyruvate kinase:
d) Regulatory enzyme of gluconeogenesis are:
i) Pyruvate Carboxylase
ii) Phosphoenol pyruvate carboxylase
iii) Fructise 1,6-bisphosphatase
iv) glucose-6-phosphatase. 51

52. REGULATION OF GLUCONEOGENESIS:
d) Regulatory enzyme of gluconeogenesis are:
i) Pyruvate Carboxylase:-
This is the key enzyme in gluconeogenetic pathways.
The enzyme is activated allosterically by acetyl Co-A.
It bind with the allosteric site of the enzyme, bring about
conformational change at tertiary level so that the affinity of
the enzyme for Co2 increases.
ii) Phosphoenol pyruvate carboxylase:-
> The enzyme is induced by Glucagon, during starvation, thus
increasing gluconeogenesis.
52

53. iii) Fructise 1,6-bisphosphatase:
This enzyme is strongly and allosterically inhibited by AMP,
but is activated by citrates. Hence Gluconeogenesis is
increased when there is increased ATP and citrate levels.
Gluconeogenesis is decreased by inhibition of this enzyme
when liver cells are rich in AMP and low in citrate
concerntration.
iv) Glucose-6-phosphatase:-
> This enzyme is induced by the hormones Glucagon and
Glucocorticoids, which are secreted during starvation thus
enhancing gluconeogenesis. Insulin repress the enzyme.
53

54. GLYCOGEN METABOLISM
Glycogen: a highly
branched polymer
of glucose. Chains
have glycosidic
links α 14.
Branches are
linked α 16.

55. Glucose stored in polymeric form as
glycogen mostly in the liver and
skeletal muscle.
 Glucose can be rapidly delivered to
the blood stream when needed upon
degradation of glycogen.
= glycogenolysis
 Enough glucose and energy triggers
synthesis of glycogen.
= glycogenesis

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