METABOLISM OF CARBOHYDRATES
Content:
Carbohydrates digestion.
Glycolysis.
Gluconeogenesis.
Pentose phosphate pathway.
Glycogenesis and Glycogenolysis.
Carbohydrates Digestion
Carbohydrate digestion start in the mouth by salivary Amylase, which breaks down starches (complex
carbohydrates) into sugars (mono- and di-saccharides) and other smaller polymers.
In stomach, low Ph blocks amylase action. (inactivated when Ph<4)
Pancreatic Amylase is secreted into small intestine and gets activated when Ph is 6.7-7.
Once sugars enter through the brush membran of intestinal epithelial cells by SGLT1 transporter.
Disaccharidases converts rest of disaccharides into monosaccharides. NOTE THAT SGLT2 IS LOCATED IN KIDNEY’S
MALTASE: Maltose>> 2x Glucose PROXIMAL TUBULE AND RESPONSIBLE FOR
GLUCOSE REABSORPTION. IT’S IMPORTANT
TO NOTE THAT MOST OF SGLT INHIBITORS
LACTASE: Lactose>> Glucose + Galactose TARGET SGLT2 EXCEPT SOTAGLIFLOZIN
AND LICOGLIFLOZIN WHICH SERVE AS DUAL
SUCRASE: Sucrose>> Glucose + Fructose SGLT INHIBITORS.
Monosaccharides are released into blood stream by GLUT2. Glucose and Galactose are absorbed by
secondary active transport system which occurs in Na/Glucose cotransporter. Fructose is absorbed by
faciliated diffusion. About 80% of absorbed monosaccharides are Glucose
Glucose transporters
wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as
facilitated diffusion.
GLUT1: Fetal tissue, erythrocytes, and epithelial cells of barriers.
GLUT2: Hepatocytes, Beta cells , renal tubular cells, and basolateral membrane of intestinal epithelium.
GLUT3: Neurons and placenta.
GLUT4: Adipose tissue and skeletal muscle.
INSULIN DEPENDENT!!!
Important notes:
GLUT1 + GLUT3 :
Found in most cells of body which makes them important in maintaing basal glucose uptake levels required to maintain
respiration in body cells at low glucose levels.
High glucose affinity (Low Km)
At normal glucose level Vmax is maintained
GLUT2
low glucose affinity (high Km)
The lower affiinity inhance their action in higher glucose levels and blocks it in low levels.
in Hepatocyte their main action is storage, while in Beta cells it controls insulin release.
Bidirectional transporter. this is especially important in hepatocytes which means glucose is released in Gluconeogenesis and
taken in for Glycolysis and Glycogenesis.
, Glycolysis
The major oxidative pathway of glucose inwhıch a series of reactıons occur to turn glucose into pyruvate.
Overview:
Occur in cytoplasm of most cells in the body
Occur in precense or absence of O2 AEROBIC GLYCOLYSIS: IN PRECENSE OF O2 AND MITOCHONDRIA.
ANEROBIC GLYCOLYSIS: ABCENSE OF O2 AND/OR MITOCHONDRIA
Rate limiting enzyme is PhosphoFructoKinase1
Glucose influx into cell through GLUT transporter then, one phosphate goup is bound to
trap it inside the cell.
Hexokinase: in most cells of body
Glucokinase: in hepatocytes and B cells.
---->This step is IRRIVERSABLE
Glucose --Fructose
İsomeratıon of glucose 6 phosphate into fructose 6 phosphate by phosphoglucoisomrase
----> This step is REVERSABLE
Another Phosphate group is added to first carbon by PhosphoFructoKinase1 to create 1,6-
bis phosohate
This is the main rate limiting step. (along with other Irriversable steps)
----> This step is IRRIVERSABLE
Fructose 1,6 bisphosphate is split into two 3Carbon molecules by Aldolase.
Glyceraldehyde 3 phosphate (G^P)
Dehydroxyacetobe phosphate (DHAP)
DHAP gets converted to G3P by Isomerase >> (also used by adipse tissue and liver for Triglyceride synthesis)
From this step every substrate is ×2
----> This step is REVERSABLE
Oxidation of 2NAD molecules into 2NADH by Trıose Phosphate
Dehydrogenase. This reaction is needed to add 2phosphate groups ınto
2G3Ps to create 1,3-bisphosphoglycerate
----> This step is REVERSABLE
1,3 bisphosphoglycerate loses one phosphate group by PhophoglyceroKinase
which leads to 3- phosphoglycerate productıon
Realeased phosphate group help turn 2ADPs into 2ATP (Substrate level
phosphorylation).
----> This step is REVERSABLE
The phosphate group get moved from the 3rd to 2nd Carbon by Mutase.
----> This step is REVERSABLE
Enolase Enzyme cleaves an H2O molecule to create Phosphoenolpyruvate
(PEP).
----> This step is REVERSABLE PYRUVATE KINASE DEFICIENCY:
IS THE SECOND MOST COMMON GENETIC DEFICIENCY THAT
PEP loses phosphate group by PyruvateKinase and Pyruvate is created. CAUSES A HEMOLYTIC ANEMIA (AFTER G6PD DEFICIENCY)
SYMPTOMS ESPECIALLY INCLUDE RBCS AS THEY
2 phosphate groups are used to turn 2ADPs into 2ATPs (Substrate level COMPLETLY RELY ON GLYCOLYSIS AS SOURCE OF ENERGY.
SYMPTOMS INCLUDE:
phosphorylation) CHRONIC HEMOLYTIC ANEMIA.
SPLENOMEGALY
----> This step is IRREVERSABLE JAUNDICE WITH KERNICTERUS RISK
FATIGUE// LETHARGY// PALLOR
İn Anerobic state// In cells with no mitochondria: FAILURE TO THRIVE IN INFANTS
GALLSTONES IN TEENS
ABCENSE OF HEINZ BODIES (UNLIKE G6PD
Lactate dehydrogenase convert Pyruvate into lactate which is the end product in these cells. DEFICIENCY)
Created NADH cannot be used in ETC however it is reoxidized to NAD to create Lactate.
Increased NAD in the cell forces Glycolysis to keep going and insure continuous energy source.
Outcomes: 4 ATPS & 2 NADHs >>> 2 ATPs consumed (by PFK2) // 2NADH consumed (by LactateDH) >>> NET: 2ATPs
gained
In Aerobic state and in cells with mitochondria:
Pyruvate enters the mitochondria to get worked by the Pyruvate Dehydrogenase complex then TCA cycle and
ETC
Outcomes of aerobic glycolysis: 4ATPs & 2 NADs >>> 2 ATPs are consumed >>> NET: 2 ATPs (substrate level
phosphorylation) & 6 ATPs (oxidative phosphorylation from NADH// Each NADH gives 3ATPs) >>> Total of 8 ATPs
Content:
Carbohydrates digestion.
Glycolysis.
Gluconeogenesis.
Pentose phosphate pathway.
Glycogenesis and Glycogenolysis.
Carbohydrates Digestion
Carbohydrate digestion start in the mouth by salivary Amylase, which breaks down starches (complex
carbohydrates) into sugars (mono- and di-saccharides) and other smaller polymers.
In stomach, low Ph blocks amylase action. (inactivated when Ph<4)
Pancreatic Amylase is secreted into small intestine and gets activated when Ph is 6.7-7.
Once sugars enter through the brush membran of intestinal epithelial cells by SGLT1 transporter.
Disaccharidases converts rest of disaccharides into monosaccharides. NOTE THAT SGLT2 IS LOCATED IN KIDNEY’S
MALTASE: Maltose>> 2x Glucose PROXIMAL TUBULE AND RESPONSIBLE FOR
GLUCOSE REABSORPTION. IT’S IMPORTANT
TO NOTE THAT MOST OF SGLT INHIBITORS
LACTASE: Lactose>> Glucose + Galactose TARGET SGLT2 EXCEPT SOTAGLIFLOZIN
AND LICOGLIFLOZIN WHICH SERVE AS DUAL
SUCRASE: Sucrose>> Glucose + Fructose SGLT INHIBITORS.
Monosaccharides are released into blood stream by GLUT2. Glucose and Galactose are absorbed by
secondary active transport system which occurs in Na/Glucose cotransporter. Fructose is absorbed by
faciliated diffusion. About 80% of absorbed monosaccharides are Glucose
Glucose transporters
wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as
facilitated diffusion.
GLUT1: Fetal tissue, erythrocytes, and epithelial cells of barriers.
GLUT2: Hepatocytes, Beta cells , renal tubular cells, and basolateral membrane of intestinal epithelium.
GLUT3: Neurons and placenta.
GLUT4: Adipose tissue and skeletal muscle.
INSULIN DEPENDENT!!!
Important notes:
GLUT1 + GLUT3 :
Found in most cells of body which makes them important in maintaing basal glucose uptake levels required to maintain
respiration in body cells at low glucose levels.
High glucose affinity (Low Km)
At normal glucose level Vmax is maintained
GLUT2
low glucose affinity (high Km)
The lower affiinity inhance their action in higher glucose levels and blocks it in low levels.
in Hepatocyte their main action is storage, while in Beta cells it controls insulin release.
Bidirectional transporter. this is especially important in hepatocytes which means glucose is released in Gluconeogenesis and
taken in for Glycolysis and Glycogenesis.
, Glycolysis
The major oxidative pathway of glucose inwhıch a series of reactıons occur to turn glucose into pyruvate.
Overview:
Occur in cytoplasm of most cells in the body
Occur in precense or absence of O2 AEROBIC GLYCOLYSIS: IN PRECENSE OF O2 AND MITOCHONDRIA.
ANEROBIC GLYCOLYSIS: ABCENSE OF O2 AND/OR MITOCHONDRIA
Rate limiting enzyme is PhosphoFructoKinase1
Glucose influx into cell through GLUT transporter then, one phosphate goup is bound to
trap it inside the cell.
Hexokinase: in most cells of body
Glucokinase: in hepatocytes and B cells.
---->This step is IRRIVERSABLE
Glucose --Fructose
İsomeratıon of glucose 6 phosphate into fructose 6 phosphate by phosphoglucoisomrase
----> This step is REVERSABLE
Another Phosphate group is added to first carbon by PhosphoFructoKinase1 to create 1,6-
bis phosohate
This is the main rate limiting step. (along with other Irriversable steps)
----> This step is IRRIVERSABLE
Fructose 1,6 bisphosphate is split into two 3Carbon molecules by Aldolase.
Glyceraldehyde 3 phosphate (G^P)
Dehydroxyacetobe phosphate (DHAP)
DHAP gets converted to G3P by Isomerase >> (also used by adipse tissue and liver for Triglyceride synthesis)
From this step every substrate is ×2
----> This step is REVERSABLE
Oxidation of 2NAD molecules into 2NADH by Trıose Phosphate
Dehydrogenase. This reaction is needed to add 2phosphate groups ınto
2G3Ps to create 1,3-bisphosphoglycerate
----> This step is REVERSABLE
1,3 bisphosphoglycerate loses one phosphate group by PhophoglyceroKinase
which leads to 3- phosphoglycerate productıon
Realeased phosphate group help turn 2ADPs into 2ATP (Substrate level
phosphorylation).
----> This step is REVERSABLE
The phosphate group get moved from the 3rd to 2nd Carbon by Mutase.
----> This step is REVERSABLE
Enolase Enzyme cleaves an H2O molecule to create Phosphoenolpyruvate
(PEP).
----> This step is REVERSABLE PYRUVATE KINASE DEFICIENCY:
IS THE SECOND MOST COMMON GENETIC DEFICIENCY THAT
PEP loses phosphate group by PyruvateKinase and Pyruvate is created. CAUSES A HEMOLYTIC ANEMIA (AFTER G6PD DEFICIENCY)
SYMPTOMS ESPECIALLY INCLUDE RBCS AS THEY
2 phosphate groups are used to turn 2ADPs into 2ATPs (Substrate level COMPLETLY RELY ON GLYCOLYSIS AS SOURCE OF ENERGY.
SYMPTOMS INCLUDE:
phosphorylation) CHRONIC HEMOLYTIC ANEMIA.
SPLENOMEGALY
----> This step is IRREVERSABLE JAUNDICE WITH KERNICTERUS RISK
FATIGUE// LETHARGY// PALLOR
İn Anerobic state// In cells with no mitochondria: FAILURE TO THRIVE IN INFANTS
GALLSTONES IN TEENS
ABCENSE OF HEINZ BODIES (UNLIKE G6PD
Lactate dehydrogenase convert Pyruvate into lactate which is the end product in these cells. DEFICIENCY)
Created NADH cannot be used in ETC however it is reoxidized to NAD to create Lactate.
Increased NAD in the cell forces Glycolysis to keep going and insure continuous energy source.
Outcomes: 4 ATPS & 2 NADHs >>> 2 ATPs consumed (by PFK2) // 2NADH consumed (by LactateDH) >>> NET: 2ATPs
gained
In Aerobic state and in cells with mitochondria:
Pyruvate enters the mitochondria to get worked by the Pyruvate Dehydrogenase complex then TCA cycle and
ETC
Outcomes of aerobic glycolysis: 4ATPs & 2 NADs >>> 2 ATPs are consumed >>> NET: 2 ATPs (substrate level
phosphorylation) & 6 ATPs (oxidative phosphorylation from NADH// Each NADH gives 3ATPs) >>> Total of 8 ATPs
