Carbohydrate Metabolism: Digestion and Absorption

Catabolism and Anabolism

• Catabolism breaks down molecules.
• Anabolism synthesizes molecules.
• This applies to sugars, glycogen, fatty acids, and amino acids.

Digestion of Carbohydrates

• Dietary carbohydrates mainly consist of polysaccharides, disaccharides, and monosaccharides.
• Polysaccharides include starch and glycogen.
• Disaccharides include sucrose (cane sugar), lactose (milk sugar), and maltose.
• Monosaccharides include fructose and pentoses.
• Liquid foods escape mouth digestion, while solid foods are masticated (chewed).
• Mouth digestion starts with saliva mixing during chewing.
• Saliva contains salivary amylase (ptyalin).

Action of Ptyalin (Salivary Amylase)

• Ptyalin is an α-amylase requiring Cl- for activation.
• Optimum pH for ptyalin is 6.7 (range 6.6 to 6.8).
• Ptyalin hydrolyzes α-1→4 glycosidic linkages randomly in starch, glycogen, etc
• This action produces smaller molecules like starches and maltose

Absorption of Carbohydrates

• Carbohydrate digestion completes in the small intestine
• Complex carbohydrates like starch and glycogen, and disaccharides, are broken down into monosaccharides
• Monosaccharides are fully absorbed from the small intestine.
• Glucose and galactose are absorbed very fast.
• Fructose and mannose absorbed at an intermediate rate.
• Pentoses are absorbed slowly.
• Absorption rates: Galactose > Glucose > Fructose > Mannose > Xylose > Arabinose

Metabolic Pathways in Carbohydrates: Glycolysis Basics

• Carbohydrate metabolism pathways begin or end with glucose.
• Glucose is a major source of metabolic energy.
• Glucose is the major form in which carbohydrates are absorbed from the intestinal tract and presented to body cells.
• Glucose is the primary fuel for specialized cells and the brain.
• The body's tissues collaborate to maintain a constant glucose supply.
• Defective glucose metabolism underlies obesity and diabetes and contributes to medical problems.
• Glycolysis is a sequence of 10 enzymatic reactions.
• One glucose molecule converts to two molecules of a three-carbon compound.

The Role and Stages of Glycolysis

• Glycolysis is key for energy metabolism by:
  • Providing energy for organisms
  • Preparing glucose and compounds for oxidative degradation
• Glycolysis breaks down glucose into pyruvate to synthesize ATP from ADP and Pi.
• Two stages of glycolysis:
  • Energy investment
  • Energy recovery
• Glycogenolysis or gluconeogenesis provide glucose.
• Glucose enters cells via specific carriers into the cytosol.
• Glycolysis enzymes loosely associate in the cytosol.
• Glycolysis converts glucose into two C3 units (pyruvate).
• The free energy results in ATP from ADP and Pi.
• Glycolysis is a chemically coupled phosphorylation.

Energy Investment and Recovery in Glycolysis

• Glycolysis has two stages:
  • Stage I: energy investment (reactions 1-5) requiring 2 ATP.
  • Stage II: energy recovery (reactions 6-10) producing 4 ATP.
• In stage I, hexose glucose is phosphorylated and cleaved into the triose, glyceraldehyde-3-phosphate.
• In stage II, two molecules of glyceraldehyde-3-phosphate convert to pyruvate, with 4 ATP generated.
• Glycolysis has a net gain of 2 ATP per glucose.
• Phosphoryl groups initially transferred from ATP do not result in high-energy compounds right away.

Significance of Glycolysis Pathway

• Glycolysis occurs in all body cells.
• The enzymes are present in the cytosomal fraction.
• Glycolysis is the only energy source in erythrocytes.
• Glycolysis occurs with or without oxygen.
• Lactate is produced under anaerobic conditions; pyruvate is produced under aerobic conditions and oxidized to CO2 and H2O.
• Glycolysis provides emergency energy for cells without oxygen.
• Glycolysis is essential for aerobic carbohydrate oxidation in cells with mitochondria.
• Glycolysis is a major pathway for ATP synthesis in tissues lacking mitochondria.
• Glycolysis provides carbon skeletons for synthesis of non-essential amino acids.
• Testes, leucocytes, and kidney medulla rely on glycolysis for ATP production.

Reactions of Glycolysis: Overview

• Glycolysis has three phases:
  • Energy investment (priming stage)
  • Splitting phase
  • Energy generation

Reactions of Glycolysis: Energy Investment Phase

• Glucose is phosphorylated to glucose-6-phosphate by hexokinase (HK) or glucokinase.
• ATP is split into ADP, adding Pi to glucose.
• Energy from ATP hydrolysis drives reaction.
• This enzyme-catalyzed regulatory step is irreversible.
• Hexokinase catalyses phosphorylation in all tissues.
  • Glucokinase catalyses glucose phosphorylation but is present in the liver.
  • Glucokinase action in the liver will also split the ATP into adenosine diphosphate
• Glucose phosphorylation traps it inside the cell.
• Glucose-6-phosphate is then trapped and metabolized.
• Glucose-6-phosphate is isomerized to reversible fructose-6-phosphate via phosphohexose isomerase and Mg2+.

Fructose-6-Phosphate Conversion and Splitting Phase

• Fructose-6-phosphate is phosphorylated to fructose-1,6-bisphosphate via phosphofructokinase (PFK).
  • PFK is an allosteric, inducible, regulatory enzyme.
  • This step is rate-limiting and irreversible in glycolysis.
  • Fructose-1,6-bisphosphatase can circumvent this step during gluconeogenesis.
• Fructose-1,6-bisphosphate (6-carbon) is cleaved into two 3-carbon units: glyceraldehyde-3-phosphate and dihydroxyacetone phosphate (DHAP).
  • This reaction is reversible with aldolase enzyme.
• Dihydroxyacetone converts to glyceraldehyde-3-phosphate by phosphotriose isomerase forming 2 molecules of glyceraldehyde-3- phosphate.
  • This is called the splitting phase.
  • The enzyme for the splitting phase is inhibited by bromohydroxyacetone phosphate.

Energy Generation Phase and Product

• Glyceraldehyde-3-phosphate is dehydrogenated and simultaneously phosphorylated to 1,3-bisphosphoglycerate.
  • The enzyme is glyceraldehyde-3-phosphate dehydrogenase and it requires NAD+.
• The product contains a high-energy bond and this is a reversible reaction. This step is important because it is involved in the formation of NADH + H+ and a high energy compound 1,3-bisphospoglycerate The enzyme phosphoglycerate kinase acts on 1,3- bisphosphoglycerate resulting in the synthesis of ATP and formation of 3-phosphoglycerate. The step is an example of substrate level phosphorylation, since ATP is synthesized from substrate without ETC involvement. Phosphoglycerate kinase is reversible. 3-phospho glycerate is isomerized to 2-phosphoglycerate by shifting the phosphate group from 3rd to 2nd carbon atom. The enzyme involved is phosphoglucomutase This is a readily reversible reaction.2- phospho glycérate is converted to phosphoenol pyruvate by the enzyme enolase One water molecule is removed. Enolase requires Mg2+, and by removing magnesium ions, fluoride will irreversibly inhibit this enzyme. Thus, fluoride will stop the whole glycolysis So when taking blood for sugar estimation, fluoride is added to blood. If not .glucose is metabolized by the blood cells, so that lower blood glucose values are obtained Phosphoenol pyruvate (PEP) is dephosphorylated to pyruvate, by pyruvate kinase First PEP id made into a transient intermediary of enol pyruvate, which is spontaneously isomerized into keto pyruvate, the stable form of purvate One mole of ATP is generated during this reaction. This is again an example of substrate level phosphorylation The pyruvate kinase is a key glycolytic enzyme This step is irreversible The reversal, however, can be brought about in the body with the help of two enzymes (pyruvate kinase and phosphoenol pyruvate carboxy kinase)

Cori's Cycle

• Cori Cycle (Lactic Acid Cycle) involves glucose conversion to lactate in muscle.
• In the liver it is re-converted to glucose.
• The body utilizes Cori's cycle to prevent lactate accumulation
• Lactate from muscle diffuses into blood, reaches the liver, and is oxidized to pyruvate.
• The pyruvate channels to gluconeogenesis.
• Regenerated glucose enters blood and returns to muscle. • In this series of five reactions, a hexose is phosphorylated, isomerized, phosphorylated again, and then cleaved to two interconvertible triose phosphates. • Two ATP are consumed in the process

Embden-Meyerhof-Parnas Pathway

This is an energy-consuming process. During exercise, lactate production is high, which is utilized by the liver to produce glucose. This process needs ATP in significant quantities, which is provided by increased metabolism leads to increased oxygen consumption. This is the explanation for the oxygen debt after vigorous exercise

Regulation of Glycolysis

• Regulatory enzymes in glycolysis:
  • Glucokinase/Hexokinase (step 1)
  • Phosphofructokinase (step 3)
  • Pyruvate kinase (step 9)
• Regulation of glucose phosphorylation:
• Feedback inhibition (hexokinase by glucose-6-phosphate) -Activated by induced by insulin (glucokinase)
• Glucokinase becomes active in the liver with high glucose Km and and low affinity.
• Glucokinase activates with more glucose.
• The glucokinase can inhibit by Glucose, it must be split the ATP for phosphorylates, liver by diameter
• Hexokinase phosphorylates glucose at low concentrations.
• Hexokinase makes glucose available in brain, cardiac, and skeletal muscle.
• Phosphofructokinase (PFK) is critical, rate-limiting.
  • ATP and citrate are key allosteric inhibitors.
  • AMP is an allosteric activator.

Metabolic Fate of Pyruvate

• The metabolic fate of pyruvate takes place under aerobic conditions
• Pyruvate converts in the liver to acetyl CoA.
• Acetyl CoA enters the TCA cycle to get oxidized into CO2.
• ATP will then generates
• Glycolis happens in the cytoplasm, therefor the pyruvate gets created in the cytoplasm
• It is then transported into the mitochondria by a pyruvate transporter
• It also converts into pyruvate dehydrogenase complex

Pyruvate Dehydrogenase Complex and Reactions

• The complex is in the mitochondria.
• Pyruvate decarboxylates to acetyl CoA by pyruvate dehydrogenase (PDH).
• PDH is multi-enzyme with 5 coenzymes and 3 apoenzymes.
• Coenzymes:
• Thiamine pyrophosphate (TPP)
• Co-enzyme A (CoA)
• FAD
• NAD+
• Lipoamide
• The enzyme parts of the PDH complex with their functions
  • Pyruvate dehydrogenase catalyzes oxidative decarboxylation
  • Dihydrolipoyl transacetylase transfers acetyl group
  • Dihydrolipoyl dehydrogenase regenerates lipoamide

Fates of Pyruvate

• Pyruvate gets converted into citirc acid after processing via aerobic conditions
• Pyruvic acid fates: undergo amination, form glucose, convert to malic acid, convert to oxaloacetic acid

Homolactic Fermentation

• In active muscle, high ATP demand, low oxygen
• ATP synthesized by anaerobic glycolysis.
• Lactate dehydrogenase catalyzes NADH oxidation by pyruvate to NAD+ and lactate. • Lactate dehydrogenase reaction is freely reversible, so pyruvate and lactate concentrations are readily equilibrated. • In pyruvate reduction by LDH, a hydride ion is stereospecifically transferred from C4 of NADH to C2 of pyruvate.
  • C: Glucose + 2 ADP + 2 Pi → 2lactate + 2ATP + 2H2O + 2H • Glucose + 2 ADP + 2 Pi → 2lactate + 2ATP + 2H2O + 2H • Lactate builds up which converts to synthesize glucose.

Alcoholic Fermentation

• Under anaerobic conditions in yeast, NAD+ for glycolysis is regenerated in a process that has been valued for thousands of years: the conversion of pyruvate to ethanol and CO₂ Yeast produces ethanol and CO₂ via two consecutive reactions 3. The decarboxylation of pyruvate to form acetaldehyde and CO₂ as catalyzed by pyruvate decarboxylase (an enzyme not present in animals).

Citric Acid Cycle (Krebs Cycle)

• The citric acid cycle can also referred to as the TCA cycle and the Krebs cycle
• Pyruvate then converts to Acetyl CoA within the citric acid cycle
• 1937 Hans Adolf Krebs studies propose the citric acid cycle as a result of his studies o oxygen

General Features of the Citric Acid Cycle

•1.The circular pathway, which is also called the Krebs cycle or the tricarboxylic acid (TCA) cycle, oxidizes acetyl groups from many sources, not just pyruvate. Because it accounts for the major portion of carbohydrate, fatty acid, and amino acid oxidation, the citric acid cycle is often considered the "hub" of cellular metabolism.

General Features

• 3 NAD+ •F*AD + GDP + Pi + acetyl-CoA 3 NADH + FADH2 + GTP + CoA + 2 CO₂. The oxaloacetate is consumed in the first step of the citric acid cycle The citric acid cycle acts as a multistep catalyst that can oxidize an unlimited number of acetyl groups • 3. Intermediaries are precursors of the biosynthesis of other compounds. • Oxidation is involved requiring four pair of electrons

• . Tca has has dual role can be
  • Catabolic: Compound from carbonhydates, lipids and proteins are oxidizes and becomes energy -Anabolic • Examples: Synthesis, forming cycles

Glycolysis and Energy Production from Glucose

Glycolysis is the only pathway that occurs in all cells of the body. It occurs both in aerobic and anaerobic conditions. When oxygen is absent, lactate is the end product, while pyruvate is the end product when oxygen is present. Glycolysis is significant for ATP production, carbon skeletons for amino acid synthesis and it provides energy to cells without mitochondria such as cornea. There is a overall energy in glycolysis with TCA cycle

Glycolysis: TCA & Inhibtitions

• The Krebs cycle is more effective in producing synthesized ATP • Inhibtited by: Cycle is used as the start point of the cycle This helps to build more ATP at every end point In the cycle there will be a CO2 formation

Amphibolic nature of TCA

(Tca is the main component of the body and that needed for the by, and that provides the carbon) • TCA provides various intermediates for the synthesis of many compounds needed by the body. • The cycle is both catabolic and anabolic in nature, hence regarded as amphibolic. Oxaloacetate and a-ketoglutarate serve as precursors for the synthesis of aspartate and glutamate

Fate of Uronic Acid

• The pathway is linked to the conversion of vitamin C
• Lack of it produces essential

Pentose Phosphate Pathway

• Also called:
  • Hexose monophosphate pathway
  • (PP-pathway
  • Phosphogluconate Pathway, etc.
• Provides an alternative pathway specifically dedicated to glucose oxidation
• It will reduce NADP
• NADPH has a role.

NADPH Importance

• NADPH from the pathway serves as a source of electrons for the reduction of molecules during biosynthesis. four and five-carbon sugars for a variety of purposes.

Glycogen Metabolism (Formations, storage & release)

• Liver have Glycogen storage form after it get process
• Glucose is mobilated before it go toward the blood and body
• Role :
  • Liver it has a available store for blood Glucose
  • protects the liver cells against the harmful effects such as as ethyl alcohol and bacterial toxins. -Certain forms of detoxification which is followed by the influence Liver

Glycogenesis and Role

Glycogenesis decreases as glycogen level increased. and the level Amino is saved to form Metabolism can forollow two phases.

Glycogen Synthesis

• Glycogen is formed from glucose liver and it oucce in tissues
• Livers synthesis involves a series of concotions from glucose
• Glycogene can can be aactivated molecule
• Requires glycogenin primer to initiate.

Glygogenesis summary

• A 6 Phosphorylation of by Gluco
• Transfer for carbon A has happened

Breakdown in glycogenesis

• By a process where there is glycogenolysis
• In skeletal muscle, it process the glycogenosis Pathway and Is is a a process the terminal that is related

Lipids Metabolism

• Lipids can be broken down as the process of stored lipids
• Fats the body: - Digesetions is insoluble because this inbile the surface exposure - Lipids and that are found for storing -Diets lipids is also a process

Digestion of lipids

• Lipase, in soluble the it's a water enzyme
• With digestion: -There is a lingual that that produce it -Free of fatty acids In stomach it mixes up

Fate of fats

• It provides some nutrients: -Satiety: Have the state of the body -It digests LIPids helps: • In man and other primates as well as guinea pigs ascorbic acid cannot be synthesised and L-Gulonic acid is oxidised to 3-keto-L- Gulonic acid, which is then decarboxylated to the pentose LXylulose.