Group Presentation (A) Group Presentation : Health Science (Gen. Nursing) Biochemistry Gluconeogenesis DR Sujuud

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Group Presentation (A)

Faculty: Health science (Gen. Nursing)


Course: Biochemistry
Lecture: Gluconeogenesis
Lecturer: Dr Sujuud
Group members
1) Ibrahim Osman Warsame
2) Ahmed Abdirisak Yusuf
3) Fadumo Abdi Mohamed
4) Abdirahiin Muhiyadiin Jodah
5) Qaali Abdi Mohamed
6) Deka Ahmed Nur
Introduction
Gluconeogenesis
• The synthesis of Glucose from non-
carbohydrate precursors mainly in the liver.
• Gluco- glucose
• Neo- new
• Genesis- mode of formation
• (Mode of formation of new Glucose)
 Gluconeogenesis, which occurs mainly in the
liver and to a small degree in the kidney, is the
synthesis of glucose from compounds that are not
carbohydrates.
 After a meal, blood glucose is supplied by
dietary carbohydrate. However, during fasting,
the liver maintains blood glucose levels by the
processes of glycogenolysis and
gluconeogenesis.
 All cells use glucose for energy; however,
the production of glucose during fasting is
particularly important for tissues such as the
brain and red blood cells.
 The major precursors for gluconeogenesis
are lactate, amino acids and glycerol.
Even-chain fatty acids do not produce any
net glucose.

 Oxaloacetate is the starting material for


gluconeogenesis
Process of Gluconeogenesis

Gluconeogenesis occurs after around 8 hours


of fasting, when liver glycogen stores start to
deplete and an alternative source of glucose is
required. It occurs mainly in the liver and to a
lesser extent in the cortex of the kidney.
REACTIONS OF GLUCONEOGENESIS

Gluconeogenesis involves several enzymatic


steps that do not occur in glycolysis; thus,
glucose is not generated by a simple reversal
of glycolysis
Three steps are different from glycolysis.
1) Pyruvate to PEP
2) Fructose 1,6- bisphosphate to Fructose-
6-phosphate
3) Glucose-6-Phosphate to Glucose
A. Conversion of pyruvate to
phosphoenolpyruvate .
1. In the liver, pyruvate is converted to
phosphoenolpyruvate (PEP) in two steps.
2. Pyruvate (produced from lactate, alanine,
and other amino acids) (Step 1) is first
converted to oxaloacetate (OAA) (Step 2) by
pyruvate carboxylase, a mitochondrial
enzyme that requires biotin and ATP .
C. Conversion of glucose 6-phosphate to
glucose
1. Glucose 6-phosphate releases inorganic
phosphate (Pi), which produces free glucose
that enters the blood. The
enzyme is glucose 6-phosphatase.
2. Glucose 6-phosphatase is involved in both
gluconeogenesis and glycogenolysis.
B. Conversion of fructose 1,6-bisphosphate to
fructose 6-phosphate .
1. Fructose 1,6-bisphosphate is converted to
fructose 6-phosphate in a reaction that releases
inorganic phosphate and is catalyzed by
fructose-1,6-bisphosphatase.
2. Fructose 6-phosphate is converted to glucose
6-phosphate by the same isomerase used in
glycolysis.
Precursors for gluconeogenesis

Lactate, amino acids, and glycerol are the major


precursors for gluconeogenesis in humans.
1) Lactate
Lactate is oxidized by NAD+ in a reaction
catalyzed by lactate dehydrogenase to form
pyruvate, which can be converted to
glucose .

Sources of lactate include red blood cells


and exercising muscle .
2) Amino acids
Amino acids for gluconeogenesis come from
degradation of muscle protein.
Amino acids are released directly into the blood
from muscle, or carbons from amino acids are
converted to alanine and glutamine and released.
Amino acids travel to the liver and provide
carbon for gluconeogenesis. Quantitatively,
alanine is the major gluconeogenic amino
acid.
Amino acid nitrogen is converted to urea.
3) Glycerol
It is derived from adipose triacylglycerols,
reacts with ATP to form glycerol 3-phosphate,
which is oxidized to DHAP and converted to
glucose. glycerol released from the
breakdown of triglycerides in adipose tissue
and amino acids (mainly alanine).
Biomedical Important of Glucose

• Glucose is a major carbohydrate


• It is a major fuel of tissues
• It is converted into other carbohydrates
• Glycogen for storage
• Ribose in nucleic acids
• Galactose in lactose of milk
• They form glycoproteins and proteoglycans
• They are present in some lipoproteins
(LDL)
• Present in plasma membrane; Glycocalx
• Glycophorin is a major integral membrane
glycoprotein of human erythrocytes.
Roles of Gluconeogenesis

• Provides Glucose for the brain


• Recycles lactate after exercise
• Lactose synthesis in ruminants
• Carbohydrate polymers in plants and
bacteria.
BLOOD GLUCOSE LEVELS

Blood glucose levels in the fed state

1) Changes in insulin and glucagon levels.


A) Blood insulin levels increase as a meal is
digested, following the rise in blood glucose.
i. Glucose enters the pancreatic b cells via the
insulin-independent glucose transporter,
GLUT-2, which stimulates release of
preformed insulin and promotes the synthesis
of new insulin.
ii. Additionally, amino acids (particularly
arginine and leucine) cause the release of
preformed insulin from b cells of the pancreas,
although to a lesser extent than that released by
glucose .
B) Blood glucagon levels change depending
on the content of the meal.
I. A high-carbohydrate meal causes glucagon
levels to decrease.
II. A high-protein meal causes glucagon to
increase.
III. On a normal mixed diet, glucagon will
remain relatively constant after a meal, while
insulin increases.
2) In muscle, insulin stimulates the synthesis of
glycogen.
3) Adipose cells convert glucose to the glycerol
for synthesis of triacylglycerols.
4. Return of blood glucose to fasting level
i. The uptake of dietary glucose by tissues
(particularly liver, adipose, and muscle) causes
blood glucose to decrease.
ii. By 2 hours after a meal, blood glucose has
returned to the fasting level of 5 mM or 80 to
100 mg/dL .
Functions Of the Liver

• Metabolic function
• Storage
• Detoxification
• Digestive function
• Excretory function
• Homeostatic function
Metabolic functions of the Liver
 Glycogenesis
- Glucose molecules are converted to Glycogen.
- Glycogen molecules are stored in the liver.
 Glycogenolysis
- Glucose is released from the liver after
conversion from Glycogen.
 Gluconeogenesis
- Glucose is produced from fats and proteins.

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