CARBO METAL_BIOCHEMISTRY

1. Carbohydrates

2. The ATP

4. Glycolysis
Also known as
Embden-Meyerhof
pathway

5. • Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvic acid,
CH3COCOOH.
• The free energy released in this process is used to form the high-energy molecules
adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide
(NADH).
• Metabolic pathway that does not require oxygen. The wide occurrence of glycolysis
in other species indicates that it is an ancient metabolic pathway.
• In most organisms, glycolysis occurs in the liquid part of cells, the cytosol.
• The most common type of glycolysis is the Embden–Meyerhof–Parnas (EMP)
pathway, which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol
Parnas.
• It also refers to other pathways, such as the Entner–Doudoroff pathway and various
heterofermentative and homofermentative pathways.

6. Investment phase – wherein ATP is
consumed

7. Yield phase – wherein
more ATP is produced
than originally
consumed. It is
characterised by a net
gain of the energy-rich
molecules ATP and
NADH. Since glucose
leads to two triose
sugars in the
preparatory phase, each
reaction in the pay-off
phase occurs twice per
glucose molecule. This
yields 2 NADH
molecules and 4 ATP
molecules, leading to a
net gain of 2 NADH
molecules and 2 ATP
molecules from the
glycolytic pathway per
glucose.

8. The first step is phosphorylation of glucose by a family of enzymes called hexokinases to form glucose 6-
phosphate (G6P). This reaction consumes ATP, but it acts to keep the glucose concentration low,
promoting continuous transport of glucose into the cell through the plasma membrane transporters. In
addition, it blocks the glucose from leaking out – the cell lacks transporters for G6P, and free diffusion
out of the cell is prevented due to the charged nature of G6P. Glucose may alternatively be formed from
the phosphorolysis or hydrolysis of intracellular starch or glycogen.
Cofactors: Mg2+

9. G6P is then rearranged into fructose 6-phosphate (F6P) by glucose phosphate isomerase. Fructose can
also enter the glycolytic pathway by phosphorylation at this point. The change in structure is an
isomerization, in which the G6P has been converted to F6P. The reaction requires an enzyme,
phosphoglucose isomerase, to proceed. This reaction is freely reversible under normal cell conditions.

10. The energy expenditure of another ATP in this step is justified in 2 ways: The glycolytic process (up to this
step) becomes irreversible, and the energy supplied destabilizes the molecule. Because the reaction
catalyzed by phosphofructokinase 1 (PFK-1) is coupled to the hydrolysis of ATP (an energetically favorable
step) it is, in essence, irreversible, and a different pathway must be used to do the reverse conversion
during gluconeogenesis. This makes the reaction a key regulatory point. This is also the rate-limiting step.
Cofactors: Mg2+

11. Destabilizing the molecule in the previous reaction allows the hexose ring to be split by aldolase into
two triose sugars: dihydroxyacetone phosphate (a ketose), and glyceraldehyde 3-phosphate (an
aldose).

12. Triosephosphate isomerase rapidly interconverts dihydroxyacetone phosphate with glyceraldehyde
3-phosphate (GADP) that proceeds further into glycolysis. This is advantageous, as it directs
dihydroxyacetone phosphate down the same pathway as glyceraldehyde 3-phosphate, simplifying
regulation.

13. The aldehyde groups of the triose sugars are oxidized, and inorganic phosphate is added to them,
forming 1,3-bisphosphoglycerate.
The hydrogen is used to reduce two molecules of NAD+, a hydrogen carrier, to give NADH + H+ for
each triose.

14. This step is the enzymatic transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP by
phosphoglycerate kinase, forming ATP and 3-phosphoglycerate. At this step, glycolysis has reached the break-
even point: 2 molecules of ATP were consumed, and 2 new molecules have now been synthesized. This step,
one of the two substrate-level phosphorylation steps, requires ADP; thus, when the cell has plenty of ATP (and
little ADP), this reaction does not occur. Because ATP decays relatively quickly when it is not metabolized, this
is an important regulatory point in the glycolytic pathway.

15. Phosphoglycerate mutase isomerizes 3-phosphoglycerate into 2-phosphoglycerate.

16. Enolase next converts 2-phosphoglycerate to phosphoenolpyruvate.
Cofactors: 2 Mg2+, one "conformational" ion to coordinate with the carboxylate group of the substrate, and
one "catalytic" ion that participates in the dehydration.

17. A final substrate-level phosphorylation now forms a molecule of pyruvate and a molecule of ATP by
means of the enzyme pyruvate kinase. This serves as an additional regulatory step, similar to the
phosphoglycerate kinase step.
Cofactors: Mg2+

18. 3 Gross Products of Glycolysis
• 4 ATP
• 2 NADH
• 2 pyruvate molecules

19. Regulation
• Allosteric Regulation
– ATP
• High level of ATP would slow down the pathway
• High level of ADP,AMP would mean low level of ATP thus speeds up the pathway
– Hexokinase - Glucose‐6‐phosphate formation. The entry point of glucose is the formation of
glucose‐6‐phosphate. Hexokinase is feedback‐inhibited by its product, so the phosphorylation
of glucose is inhibited if there is a buildup of glucose‐6‐ phosphate.
– Phosphofructokinase
» energy charge of the cell
» is also activated by fructose‐2,6‐ bisphosphate,
» is inhibited by citrate.
– Pyruvate kinase
» ATP inhibits pyruvate kinase, similar to the inhibition of PFK.
» Pyruvate kinase is also inhibited by acetyl‐Coenzyme A.
» activated by fructose‐1,6‐bisphosphate. (feed-forward activation)

20. Fermentation
Are catabolic reaction that occur with no oxidation.
Fermentation reacts NADH with an endogenous, organic electron acceptor.
Usually this is pyruvate formed from sugar through glycolysis. The reaction produces
NAD+ and an organic product, typical examples being ethanol, lactic acid, and
hydrogen gas (H2), and often also carbon dioxide.
occurs in an anaerobic environment. In the presence of O2, NADH, and pyruvate are
used to generate ATP in respiration. This is called oxidative phosphorylation.

21. Lactate Fermentation
Homolactic fermentation (producing only lactic acid) is the simplest type of fermentation.
Pyruvate from glycolysis undergoes a simple redox reaction, forming lactic acid. Overall,
one molecule of glucose (or any six-carbon sugar) is converted to two molecules of lactic
acid:
C6H12O6 → 2CH3CHOHCOOH
It occurs in the muscles of animals when they need energy faster than the blood can supply
oxygen. It also occurs in some kinds of bacteria (such as lactobacilli) and some fungi. It is
the type of bacteria that convert lactose into lactic acid in yogurt, giving it its sour taste.
These lactic acid bacteria can carry out either homolactic fermentation, where the end-
product is mostly lactic acid, or heterolactic fermentation, where some lactate is further
metabolized to ethanol and carbon dioxide(via the phosphoketolase pathway), acetate, or
other metabolic products, e.g.:
C6H12O6 → CH3CHOHCOOH + C2H5OH + CO2

23. Alcohol Fermentation
One glucose molecule is converted into two ethanol molecules and two carbon
dioxide molecules.
It is used to make bread dough rise: the carbon dioxide forms bubbles, expanding
the dough into a foam.
The ethanol is the intoxicating agent in alcoholic beverages such as wine, beer and
liquor.
Fermentation of feedstocks, including sugarcane, corn, and sugar beets, produces
ethanol that is added to gasoline.
In some species of fish, including goldfish and carp, it provides energy when oxygen
is scarce.

24. Before fermentation, a glucose molecule breaks
down into two pyruvate molecules (Glycolysis).
The energy from this exothermic reaction is used
to bind inorganic phosphates to ADP, which
converts it to ATP, and convert NAD+ to NADH.
The pyruvates break down into two
acetaldehyde molecules and give off two carbon
dioxide molecules as waste products. The
acetaldehyde is reduced into ethanol using the
energy and hydrogen from NADH, and the NADH
is oxidized into NAD+ so that the cycle may
repeat. The reaction is catalyzed by the enzymes
pyruvate decarboxylase and alcohol
dehydrogenase.

25. Pentose Phosphate Pathway
• Alternative pathway for glycose oxidation
• Provides the cell the Energy in the form of reducing power for biosynthesis
• Produces NADPH
• Occurs in the cytosol of the cell.
glucose-6-phosphate + 2NADP+ + H2O →
ribulose-5-phosphate + 2NADPH + CO2

26. • The pentose phosphate pathway provides several molecules that are important
in biosynthesis.
• It is important in liver and mammary glands, and the adrenal cortex.
• It also produces ribose which is important for biosynthesis of nucleotides.
• is most active in tissues involved in cholesterol and fatty acid biosynthesis.

28. Gluconeogenesis
• Production of glucose.
• An anabolic pathway occur in the liver.
• Reverse reaction of Glycolysis except for step 1, 3, and 10 are
irreversible.
• GTP is the source of phosphate group.

30. Precursors for Gluconeogenesis
• Gluconeogenic precursors
– Glycerol
– Lactate
– α-Ketoacids
– Acetyl Co A and precursors of Acetyl Co A.

31. Regulation
• Glucagon
– Allosteric effectors
Inhibited by high level of ATP
Activates fructose1,6-biphosphate
Inhibits phosphofructokinase
• Substrate availability
• Allosteric Activation of Acetyl Co A
• Stimulated by high level of AMP, ADP and
P

32. Glycogen Synthesis
and
Degradation

34. Glycogenolysis
Degradation of Glycogen

37. Glycogenesis
Glycogen Synthesis

40. Glycosyl alpha 4:6
transferase
Amylo(alpha1:4 alpha1:6)
transglycosylase

41. Summary
• Glycolysis
• Hexose monophosphate p / pentose pp
• Gluconeogenesis
• Glycogenolosis
• Glycogen synthesis
• fermentation