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Glycolysis:
A metabolic pathway in which glucose is broken down by substrate-level phosphorylation and
oxidation, yielding 2 pyruvate molecules and 2 ATP per 1 glucose molecule
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Enzymes:
Rate-limiting enzyme: phosphofructokinase-1 (PFK-1)
There are three irreversible steps in the pathway of glycolysis, executed by the
following enzymes:
Glucokinase: liver and β-cells of the pancreas have a lower affinity for glucose than
hexokinases of other tissues
Low glycemia (portal blood): Glucose is available to extrahepatic tissue
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PFK-1
Pyruvate kinase
PFK-1 and hexokinase/glucokinase requireATP
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In glycolysis, the breakdown of
glucose molecules generates two net adenosine triphosphate (ATP) molecules, which provide
a readily available source of energy for various reactions in the cell, and two pyruvate
molecules, which can be further converted into lactate (used in gluconeogenesis), acetyl-CoA
(used in citric acid cycle), oxaloacetate (used in citric acid cycle), and alanine (used in
transamination reactions)
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g
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In gluconeogenesis, a process that ensures euglycemia during
fasting, glucose is synthesized from non-carbohydrate precursors such as glucogenic amino
acids (mainly alanine and glutamine), odd-chain fatty acids, glycerol, pyruvate, and lactate
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Phosphofructokinase-1 is the rate-limiting enzyme for glycolysis, while fructose 1,
6-bisphosphatase is the rate-limiting enzyme for gluconeogenesis
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Glucose can also be shunted to the pentose phosphate
pathway (also known as the hexose monophosphate shunt), which is a metabolic pathway that
generates nicotinamide adenine dinucleotide phosphate (NADPH) and ribose 5-phosphate
from glucose 6-phosphate
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Ribose 5-phosphate is required for nucleotide synthesis, while
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NADPH is required for cholesterol synthesis, steroid synthesis, reduction of glutathione, and
respiratory burst
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NADPH is required for the
reduction of glutathione, an antioxidant preventing excess hydrogen peroxide and free radicals
from damaging RBC membranes
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Glucose provides the required substrates for aerobic and anaerobic metabolism
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g
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RBCs, which lack mitochondria, depend entirely on glucose to function normally
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Insulin is released in the postprandial state for anabolic metabolism, in which glucose is broken
down to be transformed into storage forms (glycogen and fat)
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g
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Gluconeogenesis:
A series of metabolic events that allows for the production of glucose from non-carbohydrate
precursors
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Responsible enzymes are
located in the cytosol and mitochondria
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2
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4
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5
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These reactions are
energy intensive, as they rely on the consumption of high-energy molecules (GTP, ATP)
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Glucogenic amino acids: Generated from the hydrolysis of protein tissue (typically
during fasting), these amino acids are capable of being converted to α-keto acids (e
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,
oxaloacetate, α-ketoglutarate) and then to glucose
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Lactate: Via the Cori cycle, lactate
produced from anaerobic glycolysis
(mostly in skeletal muscle) is shuttled to
the liver, where it is converted to
pyruvate, which serves as the first true
substrate in gluconeogenesis
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Propionyl-CoA, formed from odd-chain
fatty acid β-oxidation, this molecule can
be carboxylated to form succinyl-CoA
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4
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5
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Phosphorylated by glycerol kinase in the liver oxidized by glycerol phosphate
dehydrogenase to dihydroxyacetone phosphate (an intermediate of glycolysis)

Gluconeogenesis reactions and regulation
1
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e
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e
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2
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Phosphate shunt:
It consists of a group of reactions in which G6P is degraded, leading to the formation of
NADPH and ribose 5-phosphate
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The needs of the cell determine which metabolic pathway is taken
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Ribose 5-phosphate is needed for synthesis
of nucleotides (e
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, DNA, RNA)
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NADPH is required for: Synthesis of fatty
acid, cholesterol, and steroid hormones

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(especially in the liver, adrenal cortex, and lactating mammary glands)
3
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4
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2
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4
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Sequence of reactions (2 phases)
1
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6-phosphogluconolactone → 6-phosphogluconate
Enzyme: 6-phosphogluconolactonase
Requires 1 H2O
6-phosphogluconate → ribulose 5-phosphate
Enzyme: 6-phosphogluconate dehydrogenase
NADP+ is reduced to NADPH + H+
CO2 is released
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Creation of ribose 5-phosphate from ribulose 5-phosphate (used for nucleotide synthesis)
2
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Ribulose 5-phosphate ⇄ ribose 5-phosphate (isomerization reaction) via ribose 5phosphate isomerase
2
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Ribose 5-phosphate + xylulose 5-phosphate ⇄ fructose 6-phosphate + glyceraldehyde
3-phosphate via transketolase (requires thiamine pyrophosphate) and transaldolase

Glycogenolysis :
Glycogenolysis and Gluconeogenesis are two different types of mechanisms that raise blood
glucose levels
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Glycogenolysis is the breakdown of glycogen occurring in the liver when blood
glucose levels drop, whereas gluconeogenesis is the synthesis of glucose from non-

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carbohydrate sources like lactic acid, glycerol, and amino acids and occurs in liver
and kidneys
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Glycogen is broken down to create glucose-6-phosphate during glycogenolysis, while
compounds like amino acids and lactic acids are converted to glucose during
gluconeogenesis
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Glycogenolysis cannot take place in muscles due to the absence of phosphatase
enzymes whereas gluconeogenesis can take place in muscle cells as well

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