1. β-Galactose

2. Galactose
Found in milk sugar (lactose)
H
H
OH
lactase OH

3. Glycolysis

4. (Active Galactose)
Lactose
Glycolysis In lactating M.G.

5.  Pathways for utilizing galactose into
G –6–P, lactose, glycogen, GAGs,
glycolipids, and in glycolysis
Glycolipids
Glycogen
2
Lactose + Glucose
In lactating Lactose synthase
Mammary Gland (Active Galactose)
1
Into Glycolysis

6.  Galactose metabolism:
1. Galactokinase
2. Galactose-1-phosphate uridyltransferase
3. UDP-galactose-4-epimerase
4. Pyrophosphorylase

7. Disorders of Galactose Metabolism
• Galactosemia is a group of disorders, which can be defined as a
congenital disease due to deficiency of an enzyme in galactose
metabolism, leading to accumulation of galactose in blood and
its reduction into the sugar alcohol “galactitol” by:
• NADPH-dependent galactose reductase that is present in neural
tissue and in the lens of the eye
• A high concentration of galactitol (hygroscopic) in the lens
causes osmotic swelling, with the formation of cataract
• The principal treatment of these disorders is to eliminate lactose
from the diet

8. Clinical Significance of Galactose Metabolism
Galactosemia
Classic Galactosemia
Galactose-1-phosphate UDP-galactose-4-
uridyl transferase defect epimerase defect
Galactokinase Deficiency
Galactosaemia
Galactokinase defect

9. Clinical Symptoms of Galactosemia
1. A failure of neonates to thrive (to develop well
and to be healthy)
2. Vomiting and diarrhea occur following
ingestion of milk, hence individuals are termed
lactose intolerant
3. Impaired liver function
4. Elevated blood galactose (Hypergalactosemia)
5. Metabolic acidosis
6. Urinary galactitol excretion and
hyperaminoaciduria

10. Clinical Symptoms of Galactosemia
7. If Galactosemia is not treated, it will produce:
• cataract (Lens obeique) ‫, المياه البيضاء‬
• blindness and
• fatal liver damage (Cirrhosis)
• Glucoma (increased intraocular pressure,
‫)المياه الزرقاء‬

11. Fructose Metabolism

12. Fructose Metabolism
• People eating diets containing large amounts of sucrose,
can utilize fructose as a major source of energy
• The pathway for utilization of fructose differs in muscle
and liver
• Muscle which contains only hexokinase can phosphorylate
fructose into F-6-P which is a direct glycolytic
intermediate

13. Glyceraldehyde
Fructose Fructose-1-
phosphate Fructose-1-
phosphate DHAP

14. Entry of fructose carbon atoms into the
glycolytic pathway (Fructolysis) in hepatocytes
B

15. Conversion of Fructose into Glucose

16. Synthesis of Fructose in Seminal Vesicles
NADPH NADP+ NAD+ NADH
Glucose Aldose reductase Sorbitol Sorbitol DH Fructose
 Estimation of seminal fructose is used as a Male
Fertility Test
 Deficiency of aldolase B (Hereditary Fructose
Intolerance) leads to:
1. Accumulation of Fructose & F–1–P
2. F–1–P inhibits glycogen phosphorylase enzyme
leading to hypoglycemia especially after
ingestion of fructose

17. Sorbitol Metabolism

18. Reduction of Glucose to Sorbitol
Aldose
Reductase

19. Metabolism of Sorbitol

20. Metabolism of Sorbitol
NADPH NADP+ NAD+ NADH
Glucose Aldose reductase Sorbitol Sorbitol DH Fructose
Aldose reductase (NADPH-linked) reduces
glucose into Sorbitol
Sorbitol dehydrogenase converts Sorbitol into
fructose

21. Metabolism of Sorbitol
 Aldose reductase is found in significant amounts in:
1. Liver
2. Seminal vesicle
3. Epithelium of the eye lens
4. Schwann cells of peripheral nerves
5. Papillae of the kidney
 While Sorbitol dehydrogenase is present only in:
1. liver
2. Seminal vesicle

22.  In Diabetes Mellitus:
 Glucose enters tissues listed above freely (requires no
insulin)
 In hyperglycemia large amounts of glucose enter these
tissues & converted into sorbitol which is dead metabolite
in the retina, kidney & peripheral nerves, due to absence
of Sorbitol DH
 Sorbitol will accumulates in these cells, causing many
physiologic & pathologic manifestation including:
1. Cataract
2. Retinopathy of eye lens
3. Peripheral neuropathy of peripheral nerves
4. Nephropathy of kidney
5. Vascular problems (Atherosclerosis)

23. Gluconeogenesis
• Definition: It is the formation of glucose from non-
carbohydrate sources
• Site: Only in Liver & Kidney
• It occurs partly in cytoplasm & partly in mitochondria
• Importance of Gluconeogenesis:
1. It is the chief source of blood glucose after the first 18
hours-fasting
2. It removes blood lactate produced by RBCs & muscles
and blood glycerol produced by adipose tissue or
absorbed by intestine

24. Enzymes of Gluconeogenesis
1. Pyruvate Carboxylase:
• Converts pyruvate to oxaloacetate
2. Phosphoenolpyruvate Carboxykinase (PEP
Carboxykinase):
• Converts oxaloacetate to PEP
3. Fructose–1,6–diphosphatase:
• To reverse F–1,6–diP into F–6–P
4. Glucose–6–phosphatase:
• To reverse Glucose–6–P into Glucose

25. & Kidney

26. • Phosphoenol pyruvate carboxykinase enzyme is
present in the cytoplasm
• Oxaloacetate cannot diffuse through the
mitochondrial membrane to the cytosol
In Cytoplasm
• This problem can be solved by the dicarboxylic acid
shuttle
In Cytoplasm
In Mitochondria
In Mitochondria

27. a
In mitochondria b
1
In cytoplasm
2
Steps of
Gluconeogenesis
3

28. Sources of Gluconeogenesis
1.Blood Lactate:
• From RBCs and exercising muscles
2.Glycerol:
• From adipose or absorbed from intestine
3.Odd chain fatty acids:
• From ruminants
4.Glucogenic Amino acids

29. Substrates for
Gluconeogenesis
2
3
4
1

30. 1
& RBCs

31. 2 (10 % of Fat)
• Incorporation of Glycerol into Glycolysis in Liver
Glycerol kinase Glycerol phosphate
dehydrogenase

32. 3 Odd chain fatty acids
• Conversion of Propionyl CoA to Succinyl CoA
-Oxidation
From Ruminants

33. 3 Conversion of Propionyl CoA to
Succinyl CoA

34. 4 Glucogenic Amino acids
• Proteins are the most important sources of glucose
during fasting after the liver glycogen is depleted
• 58% of proteins are convertible to glucose. This is
proved by the D/N ratio
• D/N ratio is the ratio between the amount of Dextrose
(D) or glucose and Nitrogen (N) in urine. it is zero in
normal animals due to absence of glucose in urine

35. 4 Glucogenic Amino acids
• An animal starved for 2 – 3 days,
pancreatectomized and given phlorizin
• The D/N ratio of this animal is 3.65/1, i.e., proteins
which contain one gram nitrogen give 3.65 grams
of glucose
• Since 100 grams of proteins contain 16 grams of
nitrogen, therefore, 100 grams of proteins can give
16 X 3.65 = 58.4 grams glucose

36. 4

37. 4 Glucogenic Amino acids
< TD>

38. Regulation of
Gluconeogenesis

39. Regulation of Gluconeogenesis
1. After carbohydrate diet, Insulin inhibits the synthesis
of enzymes of gluconeogenesis
2. During starvation, glucocorticoids, growth hormone,
glucagon and adrenaline stimulate the synthesis of
enzymes of gluconeogenesis
3. Acetyl CoA is an allosteric activator of pyruvate
carboxylase, so oxaloacetate accumulate
4. Citrate & ATP stimulate fructose–1,6–diphosphatase
5. Fructose diphosphate & AMP inhibit fructose–1,6–
diphosphatase