Carbohydrates: Structure and Function

Carbs

• Organic compounds are abundant and serve as a primary energy source
• Complex processes form, break down, and interconvert carbohydrates
• Carbohydrates are essential macronutrients found in grains, fruits, and vegetables
• The critical function of carbs is to ensure a constant glucose supply to cells
• Glucose is the primary energy source for the brain, muscles, and organs
• Carbohydrates break down into monomer glucose through digestion
• Absorbed into the bloodstream and transported to various cells and tissues

Function of Carbs

• Carbs serve as fuel and energy, with 4 kcal/g to fuel cells
• Excess glucose is stored as glycogen in the liver and muscles
• Carbs have functions beyond energy production
• These include brain function
• Formation of nucleic acids
• Involvement in cell signaling, immune system function, and connective tissue structure

Structure of Carbs

• Breakdown from macro to glucose monomers is absorbed by enterocytes into the bloodstream

Digestion and Cellular Uptake of Sugars

• Specific enzymes are required to cleave different glycosidic bonds
• Salivary and pancreatic alpha-amylase are involved
• Alpha-amylase cannot cleave 1,6 bonds; dextrins contain both 1,4 and 1,6 bonds, like isomaltose
• Glycosidases, located at the brush border of the small intestine, break complex sugars into monomers; this is progressed by enterocytes
• Examples of glycosidases include lactase (lactose to glucose and galactose), maltase (maltose to glucose x2), and sucrase (sucrose to glucose and fructose)

Exogenous Supply

• Salivary alpha-amylase starts the breakdown upon consumption
• Sucrose and lactose are further hydrolyzed in the stomach
• In the intestines, the pancreas secretes alpha-amylase to continue breakdown, then absorption occurs through the lining into the bloodstream
• The blood carries nutrients to the liver via the hepatic portal vein
• Cellulose (indigestible) moves through the GI tract, goes to the ileum, and is fermented by bacteria to intestinal villi

Monosaccharide Transport

• Conversion of disaccharides and products of starch digestion into monosaccharides attaches to the membrane of the brush border of enterocytes
• Digestive enzymes are located at the brush border and blood and lymph branches are connected to the basal side of villi
• Free monosaccharides, being polar, are repelled by enterocytes; they are transported by transporters to enter enterocytes from the lumen and exit via the basal side
• Water-soluble monosaccharides from digestion are transported across the hydrophobic plasma membrane of enterocytes
• The Na+/glucose transporter 1 (SGLT1), a symporter, takes up glucose against a concentration gradient by coupling transport to Na+
• In the cytosol, glucose and galactose are retained for the epithelium's metabolic needs, exiting the cell across the basolateral pole into the enterohepatic vein via the transporter GLUT2
• Fructose is taken up at the apical membrane by GLUT5 and is not coupled with Na+, being inefficient; a large fructose presence overwhelms the system, causing diarrhea

Glucose Transporters and Cellular Absorption

• GLUT 4 is insulin-sensitive.
• All cells use glucose to form ATP, and the brain may use ketone bodies in severe situations.
• GLUT1 is located in endothelial cells and blood-brain barriers, while GLUT3 is on neurons.

Metabolic Processes

• Entry of glucose into the cell is mediated by GLUT1
• Glucose is phosphorylated upon entry.
• Glucose converts to glucose-6-phosphate which is an irreversible and committed step, trapping glucose within the cell.
• Different pathways can occur based on cell type and demand

Glycolysis

• Glucose is converted into glucose-6-P by hexokinase (phosphorylation)
• Glucose-6-P turns into fructose-6-P
• Fructose-6-P becomes fructose-1,6-bis P through phosphorylation
• Fructose-1,6-bis P converts to pyruvate (6C to 3C x2)
• 2 NADH, 4 ATP are produced for energy
• NADH (nicotinamide adenine dinucleotide) is involved in cell respiration and ETC
• NAD+ accepts electrons to become NADH (electron carrier)

Energy Investment and Generation

• Energy investment uses 2 ATP to convert glucose to fructose 1,6-bisphosphate
• Energy generation involves fructose 1,6-bisphosphate breakdown to generate 4 ATP and 2 NADH
• The net gain is 2 ATP
• The process does not consume oxygen

Aerobic Cell Respiration

• Body cells catabolize glucose to maximize ATP generation
• The fate of glucose involves 1 glucose and 6 O2 becoming 6 CO2 and 6H2O, generating more than 30 ATP
• This process involves the TCA cycle (tricarboxylic acid cycle) and the electron transport chain (ETC)
• Pyruvate is converted to Acetyl CoA when entering the matrix, releasing carbon as CO2

Anaerobic Glycolysis

• Reactions yield NADH, FADH2, and CO2 in the TCA cycle
• Aerobic processes are far more efficient in energy generation than anaerobic processes
• ATP is generated via: absence of O2, pyruvate converted to LDH-A (lactic dehydrogenase-A) to lactate, lactate exported from cell by transporter MTC (monocarboxylate transporter), no net generation of NADH, no need for O2, RBC have no mitochondria, rely on anaerobic
• For lactate, its fate is: lactate + NAD+ -> pyruvate + NADH + H+, goes to heart muscles, resting skeletal muscles etc and can be converted into pyruvate to enter TCA if O2 available. Also, it returns to the liver to be reconverted to glucose by gluconeogenesis (making glucose from non-carb precursors) via pyruvate

Fates of Glucose

• When glucose is phosphorylated to G6P, it can be further oxidized to form pyruvate
• Pyruvate can enter the TCA cycle or be converted into lactate

Fructose Conversion

• Fructose can be converted to pyruvate, which is different from glycolysis, so it's placement is limited to the liver
• Through the GI tract, nutrients are taken orally and get through the hepatic portal vein; fructose is taken up by the liver in moderation and converted to glucose, glycogen, and lactate
• Glucose is synthesized as: fructose, galactose, xylulose and carbs, can be oxidized. When entering the bloodstream:
• Insulin is released from the pancreas and GLUT4 is insulin sensitive, promoting usage and uptake of glucose by tissues

Usage of Glucose

• Adipocytes have GLUT4 on their surface that's upregulated and translocated
• Glucose converts to glycerol, glycerol 3-phosphate (backbone for TAG), and acetyl CoA - All these factors are converted to FFA also used for TAG
• TAG can be transported by VLDL (chylomicrons) for storage
• Liver stores glucose as glycogen, and releases it back into the bloodstream when needed
• When glycogen storage is full, glucose makes fatty acids (FA) from acetyl CoA and further synthesizes into TAG
• TAG is transported out of the liver to adipocytes for further storage
• Skeletal muscles store glucose as glycogen for their use during physical exertion

Pentose Phosphate Pathway

• PPP provides NADPH (biochemical reducing agent)
• Key enzymes in antioxidant systems: glutathione reductase, glutathione peroxidase, which work together with NADPH to maintain glutathione in an oxidized/reduced state
• Glutathione is the cell's weapon to fight oxidative stress and neutralize harmful peroxidases
• It converts H2O2 to H2O
• Ribose-5-phosphate, which is produced from PPP, is a building block for nucleotides PPP converts glucose into a powerful reductant

Glycosylation of Protein

• Glucose → UDP glucose → glucuronides for detox processes or for the synthesis of glycoprotein, glycolipids, or proteoglycans in bacteria, which are building blocks of extracellular structures
• Converted to UDP galactose → lactose, sugar found in milk

Synthesized De Novo

• Cells require glucose for metabolic functions
• Neither glucose nor sugars are required from the diet
• Glucose is also synthesized from dietary protein (AA) and glycerol, e.g., lactate, alanine, glycerol
• It takes place only in the liver and kidney
• Glucose is then sent out to the bloodstream

Metabolic Actions

• Anaerobic glycolysis
• Cell respiration
• Glycogenesis
• Gluconeogenesis
• Glycogenolysis
• Glucuronidation
• NADPH production