Glycolysis is a universal pathway that converts glucose into pyruvate, generating ATP through a series of 10 enzyme-catalyzed reactions. Under aerobic conditions, pyruvate enters mitochondria and is further oxidized through the citric acid cycle and electron transport chain to harvest most energy. If oxygen is insufficient, pyruvate is reduced to lactate. Glycolysis is regulated by three irreversible reactions controlled by hexokinase, phosphofructokinase, and pyruvate kinase. Cholesterol synthesis begins with acetyl-CoA and involves 13 enzymatic steps producing isoprenoid units that ultimately form cholesterol through squalene and lanosterol intermediates.

1. BIOCHEMISTRY
Glycolysis and
related phenomena

2. AGENDA:
Glycolysis – (from the Greek words γλυκυς – sweet or
sugar; λυσις – dissolution) – is a universal pathway in
the living cell. This pathway is often reffered to as
Embden-Meyerhof pathway.

3. Glycolysis is the sequence of reactions that converts
glucose into pyruvate (or lactate) with the concomitant
productions of ATP.
In aerobic organisms, glycolysis is the prelude to the
citric acid cycle and the electron-transport chain,
which together harvest most of the energy contained in
glucose.
Under aerobic conditions, pyruvate enters
mitochondria, where it is completely oxidized to CO2
and H2O. If the supply of oxygen is insufficient, as in
actively contracting muscle, pyruvate is converted into
lactate. In some anaerobic organisms, such as yeast,
pyruvate is transformed into ethanol.

4. Glycolysis is listed among major pathways of carbohydrate
metabolism, mainly they are as follows:
-glycolysis (oxidation of G[lucose] to pyruvate/lactate)
-citric acid cycle (oxidation of Acetyl-CoA to CO2)
-gluconeogenesis (synthesis of G from non-carbonic precursors: amino
acids, glycerol etc.)
-glycogenesis (formation of glycogen from G)
-glycogenolis (breakdown of glycogen to G)
-galactose methabolism (conversion of galactose to G and synthesis of
lactose)
-fructose metabolism (oxidation of fructose to pyruvate)
-hexose monophosphat shunt (pentose phosphat pathway of G direct
oxidation to CO2 andH2O)
-uronic acid pathway (convertation of G to glucuronic acid, pentoses
[even to ascorbinic acid but not in man!])
-amino sugar and mucopolysaccharide metabolism (the synthesis of
amino sugars for the formation of mucopolysaccharides and
glycoproteins).

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6. Pyruvate (pyruvic acid) and related compounds

7. Main types of glycolysis reactions
(1) – Phosphoryl transfer
– phosphoryl group is transferred from ATPtoa
glycolitic intermediate, or vice versa

8. Main types of glycolysis reactions
(2) – Phosphoryl shift
– phosphoryl group is shifted within a molecule from
one oxygen atom to another

9. Main types of glycolysis reactions
(3) – Isomerization
– a ketose is converted into aldose, or vice versa

10. Main types of glycolysis reactions
(4) – Dehydratation
– a molecule of water is eliminated

11. Main types of glycolysis reactions
(5) – Aldol cleavage
– a carbon-carbone bond is split in a reversal of an
aldol condensation

12. Fates of Glucose

13. There are two pathways of glycolysis reactions:
-anaerobic (absence of oxygen: leads to lactate)
-aerobic (presence of oxygen: lead to pyruvate)
[dichotomic degrading: διχα- – divided into two parts]
[apotomic degrading: απο- – cleavage]
– glycolysis is a pathway for ATPsynthesis in tissues
lacking mitochondria (erythrocytes, cornea, lens etc)
– glycolysis is essential for brain
– glycolysis is a central metabolic pathway with many
intermediates providing branch point to other
pathways

14. Main
features of
Glycolysis

15. Generally the glycolysis pathway can be divided into
three distinct phases
I.Energy investment phase (G is irreversibly
phosphorylated to Glucose 6-phosphate by hexokinase or
glucokinase [isoenzymes] dependent on ATPand Mg2+)
II.Splitting phase (six carbon fructose 1,6-bisphosphate is
split by aldolase [hence the name lysis] into two three-carbon
compounds: glyceraldehyde 3-phosphate and
dihydroxyacetone phosphate)
III.Energy generating phase (glyceraldehyde 3-phosphate
dehydrogenase converts glyceraldehyde 3-phosphate to
1,3-bisphosphoglycerate it is involved in the formation of
NADH+H+ and high energy compound: 1,3-bisphospho-
glycerate [iodoacetate and arsenate inhibit the enzyme])

16. Glucose → Glucose 6-phosphate [1°-irreversible]
(hexokinase) [+ATP+divalent metal]
Hexokinase (glucokinase) – like
all other kinases, requires Mg2+
(or another divalent metal ion
such as Mn2+)

17. Glucose 6-phosphate → Fructose 6-phosphate [2°]
(phosphoglucose isomerase)

18. Fructose 6-phosphate → Fructose 1,6-bisphosphate
[3°-irreversible]
(phosphofructokinase) [+ATP Mg2+]

19. Fructose 1,6-bisphosphate →
Dihydroxyacetone phosphate [4°]
+ Glyceraldehyde 3-phosphate (aldolase)
triose phosphate [phosphotriose] isomerase convert
Dihydroxyacetone phosphate to Glyceraldehyde 3-phosphate

20. Glyceraldehyde 3-phosphate
oxydated →
1,3-bisphosphoglycerate [5°]
(Glyceraldehyde 3-phosphate
dehydrogenase)
[+NAD+Pi]

21. 1,3-bisphosphoglycerate →
3-phosphoglycerate [6°]
(phosphoglyceratekinase)
[ADP (Mg2+) → ATP]

22. 3-phosphoglycerate → 2-phosphoglycerate [7°]
(phosphogyceromutase)

23. 3-phosphoglycerate → phosphoenolpyruvate [8°]
(enolase) [Mg2+]

24. Phosphoenolpyruvate → pyruvate [9°-irreversible]
(pyruvatekinase) [ADP (Mg2+) → ATP]

25. Summary for glycolysis
reartions:
Glucose
+ [2ADP + 2NAD+ + 2Pi ] →
2 Pyruvate
+ [2ATP + 2NADH + 2H+ + 2H2O]

26. Generation of ATP in Glucose metabolism

27. Regulation of glycolysis
The three enzymes:
Hexocinase (and glucokinase)
Phosphofructokinase
Pyruvate kinase
are catalysing the irrevrsible reactions, what can be
considered as regulation of glycolysis
Hexokinase – is inhibited by glucose-6-phospate
Phosphofructokinase – allosteric enzyme regulated by allosteric
effectors, most important regularory enzyme in glycolysis – it catalyses the rate limiting
committed step, inhibited by ATP,citrate and H+ ions (low pH); fructose 2,6-
bisphosphate,ADP,AMP and Pi – are allosteric activators
Pyruvate kinase – is inhibited by ATPand activated by fructose1,6-
bisphosphate

28. Regulation of fructose 2,6 bisphosphate
Phospho-fructokinase 2
– allosteric enzymeregulated
by allosteric effectors, most
important regularory enzyme
in glycolysis – it catalyses the
rate limiting committed step,
inhibited by ATP,citrate and
H+ ions (low pH); fructose
2,6-bisphosphate, ADP,AMP
and Pi – are allosteric
activators
[in fact, the combined name of
phosphofructokinase 2/fructose
2,6 bisphosphatase is used to
refer to the enzyme that synthesis
and degrades fructose 2,6
bisphosphate – bifunctional
enzyme]

29. Regulation of pyruvate kinase
pyruvate kinase
– is inhibited by ATP,and
activated by
fructose 1,6-bisphospate.
pyruvate kinase is actove
(a)in dephosphorylated
state and inactive (b) in
phosphorylated state.
Inactivation of pyruvate
kinase by phosphorylation
is brought about by
cAMP-dependent protein
kinase. The hormone –
glucagon – inhibits
hepatic glycolysis by this
mechanism

30. Regulation of glycolysis
Pasteur effect – inhibition of glycolysis by oxygen (aerobic
condition)
Crabtree effect – the phenomenon of inhibition of oxygen
consumption by the addition of glucose to tissues having high aerobic
glycolysis. This is opposite to the Pasteur effect – is due to increased
competition of glycolysis for inorganic phosphate (Pi) and NAD+ which
limits their availability for phosphorylation and oxidation.

31. Rapaport-Leubering cycle
for the synthesis of 2,3-
bisphosphoglycerate
This is a supplementary pathway to
glycolysis which is operative in the
erythrocytes of man and other mammals.
This cycle is mainly concerned with the
synthesis of 2,3-bisphosphoglycerate in
the red blood cells.

32. Pyruvate (enol) → Pyruvate (keto)
(spontaneously) and → L-Lactate (lactate
dehydrogenase)

33. Main source of Glucose for glycolysis is Glycogen

34. Some poli- and disaccharides are hydrolyzed to
monosaccharides which directly cannot enter the
glycolysis.

35. Entry of
Fructose,
Galactose,
and
Mannose
into
Glycolysis

36. Galactose → Glucose
(uridin diphosphate [UDP] + NAD+)

37. Pyruvate is the main source of Acetyl-CoA
(catalyzed by pyruvate dehydrogenese)

38. Conversion of pyruvate to acetyl CoA
Pyruvate is conversed to acetyl CoA by oxidativedecarboxylation.
This is an irreversible reaction, catalysed by a multienzyme complex –
pyruvate dehydrogenase complex, which is found in the mitochondria.
High activities of pyruvate dehydrogenase complex are found in cardiac
muscle and kidney. It requires five cofactors (coenzymes): thiamine
pyrophosphate (TPP), lipoamide, flavin adenin dinucleotid(FAD),
coenzyme A, and nicotine adenin dinucleotid (NAD+) - (lipoamide
contains lipoic acid linked to ε-amino group of lysine)

39. Fatty acids –
by reactions of β-oxidation,
also, –
leads to Acetyl-CoA

40. Acetyl-CoA it the main source of Energy

41. Cycle of citric acid
(Kreb’s cycle)
[tricarboxylic acid
cycle]

42. and it is a starting point of some very important
substance synthesis
named
CHOLESTEROL
it leads to steroid hormones,
bile acids,
membrane construction
It is very important in genesis of vascular pathology

43. Cholesterol synthesis pathway
isoprenoid unit (5C)
(isopren СН2=С(СН3)-СН=СН2)

44. Cholesterol (1-step) Acetoacetyl CoA (thiolase)

45. Cholesterol (2-step) β-hydroxy β-methylglutaryl CoA
(hydroxy-methylglutaril CoA synthase)

46. Cholesterol (3-step) mevalonate (6C)
(β-hydroxy β-methylglutaril CoA reductase)
Hydroxy-
methylglutaril CoA
reductase is
inhubited by
statins and fibrates

47. Cholesterol (4-step) 5-phosphomevalonate (6C)
(mevalonate kinase)

48. Cholesterol (5-step) 5-pyrophosphomevalonate (6C)
(phosphomevalonate kinase)

49. Cholesterol (6-step)
3-phospho 5-pyrophosphomevalonate (kinase)

50. Cholesterol (7-step) isopentenyl pyrophosphate (5C)
(pyrophosphomemalonate decarboxylasae)

51. Cholesterol (8-step) dimethylallyl pyrophosphate (5C)
(isopentenyl pyrophoshate isomerase)

52. Cholesterol (9-step) geranyl pyrophosphate (10C)
(cis-prenyltransferase)

53. Cholesterol (10-step) farnesyl pyrophosphate (15C)
(cis-prenyltransferase)
+ dimethylallyl pyrophosphate (5C)

54. Cholesterol (11-step) squalene (30C)
(squalene synthase)

55. Cholesterol (12-step) lanosterol (30C)
(epoxidase+hydrolase+cyclase)

56. Cholesterol (13-step + ~ 19 reactions) cholesterol (27C)
(with different enzymes participation)

57. Cholesterol structure

58. Thank YOU for ATTENTION