IV: Carbohydrates

Carbohydrates

Carbohydrates

Complex organic compounds composed of carbon, hydrogen, & oxygen

Carbohydrates

-    Along with lipids & proteins, provide energy & contribute to the structure of organisms. 

Carbohydrates

-    Contain a carbonyl (C=O) & a hydroxyl (-OH) functional groups.

Glucose

-    Carbohydrate primarily consumed by the human body.

Glucose

-    Can enter RBCs freely.

Glucose

-    In some tissues (skeletal, muscle, adipose), in which glucose can only enter with the help of insulin by stimulating the expression of glucose transporter 4 (GLUT4).

Brain

2/3

is completely dependent on glucose for energy production.- of glucose utilization in resting adults occurs on the CNS.

GLUT4

It is known as a solute carrier.

Triose

Classification of Carbohydrates

According to Number of Carbons

Carbons – Gylceraldehyde

Tetrose

Classification of Carbohydrates

1. According to Number of Carbons

·    4 Carbons – Erythrose

Pentose

Classification of Carbohydrates

1. According to Number of Carbons

·    5 Carbons – Ribose, Xylose, Arabinose

Hexose

Classification of Carbohydrates

1. According to Number of Carbons

6 Carbons – Glucose, Lactose, Galactose, Fructose

Heptose

Classification of Carbohydrates

1. According to Number of Carbons

·    7 Carbons – Sedoheptulose

Aldose

Classification of Carbohydrates

Location of C=O functional Group   

·    contains a terminal C=O functional group (aldehyde)

Ketose

Classification of Carbohydrates

Location of C=O functional Group

contains a middle C=O functional group (ketone)

Monosaccharide

Classification of Carbohydrates

Number of Sugar Units    

·    1 sugar

D-glucose

is the principal monosaccharides in the plasma; can be directly utilized by cells as source of energy. Other monosaccharides must be converted first to glucose before they can be utilized by cells.

Disaccharides

Classification of Carbohydrates

Number of Sugar Units  

·    2 sugars

Sucrose (Table Sugar)

Classification of Carbohydrates

Number of Sugar Units  

Disaccharides

·   Glucose + Fructose =

Lactose (Milk Sugar)

Classification of Carbohydrates

Number of Sugar Units  

Disaccharides

Glucose + Galactose=

Maltose

Classification of Carbohydrates

Number of Sugar Units  

Disaccharides

·   Glucose + Glucose =

Oligosaccharides

Classification of Carbohydrates

Number of Sugar Units  

·    3-10 sugar units

Polysaccharides

Classification of Carbohydrates

Number of Sugar Units 

·    linkage of many monosaccharides; Glycogen, Starch, Cellulose (plants), Chitin (fungi).

Glycogen

85%

15%

Classification of Carbohydrates

Number of Sugar Units

Polysaccharides

·   major storage form of glucose in man.

-         Major site of storage:

·    Liver – -

·    Skeletal muscles – -

·   Dextrorotatory (D)

Classification of Carbohydrates

Stereochemistry of the Compound 

if projection of the last –OH group is on the right

·   Levorotatory (L)

Classification of Carbohydrates

Stereochemistry of the Compound

if projection of the last –OH group is on the left

·    Energy source

·    Component of nucleic acids (ribose, deoxyribose)

·    Modifications of proteins through glycosylation

Functions of Carbohydrates

Glycemic control

-        is important in diabetes because hyperglycemia leads to development & progression of microvascular (nephropathy, retinopathy, neuropathy) & macrovascular (atherosclerosis 2-4x) complications

Polysaccharides

disaccharides

Carbohydrate Metabolism 

- & - are non-absorbable polymers which must be converted first into monosaccharides before being absorbed in the small intestine.

·   Pyruvic acid

·   Lactic acid

·   Acetylcoenzyme A

Carbohydrate Metabolism

-    Intermediate products of glucose metabolism:

·   CO2

·   Water

·   Adenosine Triphosphate (ATP)

Carbohydrate Metabolism

-    End products of glucose metabolism:

Pancreatic & salivary amylases

Enzymes Responsible for CHO Catabolism  

-    converts nonabsorbable polysaccharides into disaccharides & dextrins.

Maltase, Sucrase & Lactase

Enzymes Responsible for CHO Catabolism  

-    converts maltose, sucrose & lactose into monosaccharides.

-    Happens in the microvilli of small intestine.

-    Inherited deficiencies of lactase predispose an individual to lactose intolerance.

t

Fate of Glucose (t/f)

·    Ingested polysaccharides (starch) is converted by salivary amylase into disaccharides & dextrin’s.

F

-    No CHO degradation happens in the stomach since salivary amylase inactivated by gastric juice (pH of 1-3 due to HCl)

Fate of Glucose (t/f)

·    Disaccharide & dextrins are further catabolized by pancreatic amylase into absorbable monosaccharides (lactase, sucrase, & maltase) by gut derived enzymes.

-    CHO degradation happens in the stomach since salivary amylase inactivated by gastric juice (pH of 1-3 due to HCl)

T

Fate of Glucose (t/f)

·    Absorbed monosaccharides (glucose, fructose, galactose) migrate to the liver via hepatic portal vein & enters bloodstream causing postprandial hyperglycemia.

F

·    Pancreatic beta cells senses hyperglycemia & secretes insulin.

Fate of Glucose (t/f)

·    Pancreatic beta cells senses hyperglycemia only.

T

Fate of Glucose (t/f)

·    Insulin-mediated activities – Glycolysis, glycogenesis & lipogenesis are stimulated.

F

·    Glucose level normalizes to baseline level (normoglycemia). This entire process takes an average of 2 hours for most adults.

Fate of Glucose (t/f)

·    Glucose level normalizes to baseline level (normoglycemia). This entire process takes an average of 5 hours for most adults.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway 

·    Phosphorylation of Glucose on C6 into glucose-6-phosphate by hexokinase (this process traps glucose inside the cell)

Phosphorylation

-    chemical process to add phosphate into an organic compound.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

Isomerization of glucose-6-phosphate to fructose 6-phosphate by phophoglucoisomerase/isomerase

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·    Phosphorylation of fructose 6-phosphate on C1 forming fructose-1,6-biphosphate by phosphofructokinase.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

Split of fructose-1,6-biphosphate into isomers dihydroxyacetone phosphate (DHAP) & glyceraldehyde 3-phosphate (GAP) by aldolase.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

Conversion of DHAP into GAP by the action of the enzyme triose-phosphate isomerase.

Gap

substrate for next step in glycolysis so all DHAP is eventually depleted. So, 2 molecules of GAP are formed from each molecule of glucose.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·    Dehydrogenation & C1 phosphorylation of GAP into 1,3-biphosphoglycerate by enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH).

-    In the process, NAD+ is reduced to NADH+ H+

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·    Hydrolysis of the high energy bond at C1 by phosphoglycerate kinase yielding ATP & the product 3-phosphoglycerate.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·    Shifting of phosphate from C3 to C2 forming 2-phosphoglycerate by phosphoglycerate mutase.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·    Dehydration of 2-phosphoglycerate by enolase forming phosphoenolpyruvate.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

Hydrolysis of the high energy bond yielding pyruvate & ATP by the enzyme pyruvate kinase.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·    Pyruvate enters the mitochondrion & is converted into acetylcoenzyme A.

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·    Acetylcoenzyme A then enters the citric acid cycle (tricarboxylic acid (TCA) / Krebs Cycle) where it is oxidized into CO₂, H₂O, & ATP.

Glycolysis (EMP Pathway)

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·    – is considered Anaerobic.

-    In the presence of oxygen, pyruvate is further oxidized to CO₂.

-    In the absence of oxygen, pyruvate can be fermented to lactate & ethanol.

Glycolysis (EMP Pathway)

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·   Pentose Phosphate Shunt/Hexose Monophosphate Pathway – responsible for synthesis of reduced glutathione & NADPH to protect cells from oxidative stress.

·   Methemoglobin Reductase Pathway – Maintains iron in the ferrous (Fe2+) state since ferric (FE3+ are incapable of binding oxygen.

Luebering-Rapoport Pathway

Embden-Meyerhof Parnas-Pathway / Hexose Monophosphate Pathway

·   - – responsible for synthesis of 2,3-diphosphoglycerate to enhance oxygen to tissues.

-    Hemoglobin has higher affinity to 2,3-DPG than oxygen.

Pancreas

-    Both an endocrine & exocrine gland.

Islets of Langerhans

Endocrine pancreas is

Beta Cells

·   insulin, islet of amyloid polypeptide (IAPP) or amylin.

Alpha Cells

glucagon (also by L cells)

Delta Cells

somatostatin & largest in size

PP/F cells

·   pancreatic polypeptide (Gamma cells)

5:1 to 15:1

What is the C-peptide: insulin ratio:

Duct & Acinar cells

Exocrine pancreas is

Duct cells: Bicarbonate Ions

secretion controlled by secretin.

Acinar cells: Digestive enzymes

·   pancreatic amylase, lipase, trypsinogen & chymotrypsinogen.

-   Secretion controlled by cholecystokinin (formerly pancreozymin) 

Glycolysiss

Pathways in Glucose Metabolism

Metabolism of glucose molecule to pyruvate/lactate for production of energy.

Gluconeogenesis

Pathways in Glucose Metabolism

Formation of glucose 6-phospohate from non-carbohydrate sources.

Glycogenolysis

Pathways in Glucose Metabolism

Breakdown of glycogen to glucose for use as energy.

Glycogenesis

Pathways in Glucose Metabolism

Conversion of glycogen for storage

Lipogenesis

Pathways in Glucose Metabolism

Conversion of CHO to fatty acids

Lipolysis

Pathways in Glucose Metabolism

Decomposition of fats

During Post-Prandial State

Glucose Metabolism

-    ↑ insulin to glucagon ratio = anabolism

-    Anabolism

-    Increase insulin to glucagon ratio

Glycogenesis

hyperglycemia stimulates insulin secretion promoting cellular uptake of glucose in insulin-sensitive tissues.

During Short Fasting State

Glucose Metabolism

-    ↓ insulin to glucagon ratio = catabolism

Glycogenolysis

Glucose Metabolism

Blood glucose level is kept constant by mobilizing glycogen stores in liver.

Catabolsim

decrease insulin to glucagon ratio

During Long Fast State

Glucose Metabolism

-    >1 day

Gluconeogenesis

Glucose Metabolism

-    body uses glucose from non-carbohydrate sources (amino acids, glycerol, pyruvate).

Insulin  

-    Peptide hormone produced by Beta Cells of pancreas

Insulin  

-    Secreted in high amount after meals

Insulin  

Processed from a larger precursor molecule called proinsulin in beta cells.

Proinsulin  

Insulin  

-    Proinsulin – is cleaved into insulin & C-peptide.

Insulin  

    The only hypoglycemic hormone (lessen glucose in the body)

C-peptide & insulin

5:1 to 15:1

Insulin  

-    - & - are secreted in equimolar amounts into the portal vein, but ratio in serum is about - to - . This is due to the hepatic clearance of insulin.

Insulin  

-    Primary hormone responsible for the entry of glucose into the cell.

·    Promotes cellular entry of glucose into the insulin-sensitive tissues (liver, skeletal muscle & adipose) as energy source through glycolysis.

·    Promotes glycogenesis

·    Promotes lipogenesis

·    Inhibits glycogenolysis

Actions of Insulin     

1. Glucagon   

2. Somatostatin    

3. Cortisol (Glucocorticoids)

4. Epinephrine    

5. Thyroxine     

6. Adenocortitrophic Hormone (ACTH)     

7. Growth Hormone (Somatotrophin)      

8. Human Placental Lactogen      

What are the Hyperglycemic Hormone 

Glucagon   

-    Primary hyperglycemic hormone

Glucagon   

-    Secreted by the alpha cells of the Islet of Langerhans of the pancreas & the L cells of the small distal bowel.

L Cells

Glucagon   

-   - – secrete glucagon like peptide 1.

Glucagon   

-    Released during stress, & fasting state.

Glucagon   

-    Increases plasma glucose levels by promoting glycogenolysis in the livers & increasing gluconeogenesis.

Somatostatin

-    Synthesized by delta cells which are 5-10% of the islet cells.

Somatostatin

-    A major inhibitory hormone.

Somatostatin

-    It inhibits pituitary (growth hormone & thyrotropin) & hormone (insulin, glucagon, PP) hormones.

Somatostatin    

increase

-    Net effect on glucose level = -

Pancreatic peptide

Somatostatin    

- – suppresses insulin secretion, thus raised blood glucose levels.

Cortisol (Glucocorticoids)    

-    Secreted by the zona fasiculata of adrenal cortex.