Carbohydrate Metabolism

Summary

This lecture will review all the ways in which carbohydrates are taken into, stored, and metabolized within the human body.

We will start off with a review of the different ways that carbohydrate structures can be arranged. We follow that with an overview of the digestive system and how carbohydrates are broken down and then absorbed through the epithelial lining into the body. We will explore the organs and enzymes involved in that process.

Next, we will look at the enzymatic reactions that are responsible for taking glucose and converting it into cellular energy (ATP). Specifically we will explore glycolysis, the citric acid cycle, the electron transport chain, and ATP synthesis.

We will discuss another pathway through which 5-10% of all glucose is metabolized, the pentose phosphate pathway, and why it is so critical for many other functions in the body.

From there, we will look into how the body stores excess glucose, through the formation of glycogen, and also through the conversion to fatty acids for storage as fat.

Lastly, we will explore how the body can create new glucose when it needs to. Specifically we will discuss glycogenolysis and gluconeogenesis.

Key take aways

• Know the basic structure of carbohydrates
• Understand how carbs are digested and taken into the body
• Understand the process of how a glucose molecule in converted into cellular energy (ATP)
  • Glycolysis
  • Pyruvate conversion to Acetyl-CoA
  • The citric acid cycle
  • The electron transport chain
  • ATP synthesis
• Explain how Anaerobic metabolism is different from aerobic metabolism
• Know the critical functions of the Pentose Phosphate pathway
• Understand how glucose is stored by the body
• Learn how the body can create new glucose molecules

[Metabolism Key Terms]

Goals

• Learn the basics of structure, digestion, uptake, Metabolism and storage for carbohydrates
• Learn the process of how a glucose molecule in converted into cellular energy (ATP)
• Understand how glucose is stored by the body
• Learn how the body can create new glucose molecules

Carb Structure

Couple different organizations

Simple

Monosaccharides - glucose, fructose, galactose Disaccharides - maltose, sucrose, lactose

Complex

Starch, glycogen, fiber

Macroglycogen is the big structure of glycogen.

Organs Involced in Digestion

System 1: Gastrointestinal tract, otherwise called the [alimentary canal]

• A continuous tube that extends from the mouth to the anus through the thoracic & abdominopelvic cavities
• Organs include the mouth, most of the pharynx, esophagus, stomach, small intestine, & large intestine
• Length of the GI tract is about 5–7 meter

System 2: Accessory digestive organs

• Teeth
• Tongue
• Salivary glands initializes digestion of starches through enzymes
• [Liver]
• [Gallbladder]
• [Pancreas]
  • Buffers acidic gastric juice in [chyme]
  • Stops the action of pepsin from the stomach
  • Creates the proper pH for digestion in the small intestine
  • Participates in the digestion of carbohydrates, proteins, triglycerides

makes enzymes: [Lipase], [Protease], [Amylase]

As well as hormones:

• Insulin
• Glucagon
• Gastrin
• Amylin

Carb Digestion

• Most dietary carbs come in the form of ‘starches’
  • Glucose units arranged into long chains, also called amylose
• Salivary and pancreatic [amylase] break down the starch, resulting in progressively smaller chains of glucose

“-ase” means it’s an enzyme

• Digestion is completed by epithelial cell enzymes resulting in simple sugars that can be absorbed
  • Maltose is broken down into 2 glucose molecules
  • Lactose is broken into glucose and galactose
  • Sucrose is broken down into fructose and glucose

Carb Absorption in the intestine

Movement of glucose is followed by the movement of sodium in a cell. (energy + sodium)

Carbohydrate Metabolism

Aerobic Metabolism - 4 step process

Glycolysis

Glucose broken down to Pyruvate
Make a little [[ATP]] and [[NADH]] (electron transportation molecule)

- Glucose is transported into the cell through GLUT2 and immediately phosphorylated (to trap it inside the cell) forming Glucose- 6P

- At this point, two different types of a process called “Glycolysis” can occur
- Aerobic glycolysis: 6C Glucose is split into 2 3C [[pyruvate]]

1 round of Glycolysis gives you 2 molecules of [[pyruvate]], 2 molecules of [[ATP]], 2 molecules of [[NADH]]

[The Citric Acid Cycle] - Krebs cycle

Need to move [[pyruvate]] into mitochondria

Creates more [[NADH]] as well as [[FADH2]]
and some [[ATP]]
as well as CO2

2 carbon molecule - [[COA]] -entry point for the Citric Acid Cycle
- In aerobic state, 3C pyruvate is converted into a critical molecule called Acetyl-CoA (2C) + C02
- A) This step proceeds twice for every molecule of glucose metabolized
- Acetyl-CoA is the entry point for the next step, called “The Citric Acid Cycle”
- B vitamins are CRITICAL in this process

• Citric Acid Cycle A complex series of enzymatic reactions that take the two carbons from Acetyl- CoA, and release them as CO2
• Each “turn” of the cycle results in two CO2 molecules + two other compounds called NADH and FADH2, which are further processed in the electron transport chain
• Small amounts of ATP are also generated

Electron Transport Chain and Oxidative Phosphorylation

A series of proteins designed to pass electrons and produce a bunch of ATP Electron transport chain establishes proton gradient that is used to produce ATP

• Oxidative phosphorylation is the metabolic pathway where electrons are transferred from NADH and FADH through a series redox reactions

• The electron transport chain is used to pump hydrogen ions across the inner mitochondria membrane, establishing an electrochemical gradient

Cells don’t like the imbalance that this creates. This forces hydrogen down through ATP Synthase that converts ADP to ATP

Anaerobic Metabolism - Humans

• When energy demands are high, say during high intensity training, free NAD becomes limiting
• Instead of converting Pyruvate to Acetyl-CoA, it can be fermented into Lactate
• Lactate + NADH <-> Lactic Acid + NAD+
• Lactic acid travels to the liver where it is converted back to pyruvate

Anaerobic Metabolism- Yeast

• Yeast have a different fermentation product
• When oxygen is limiting, yeast will convert pyruvate to ethyl alcohol and produce CO2
• This is how beer is made

[Pentose Phosphate Pathway]

run in every single cell in the body (even red blood cells)

• Creates reducing a reducing agent called NADPH (anti-oxidant like function)
  • NADPH is used for nitric oxide synthesis, steroid hormone synthesis, cortisol synthesis, bile acid synthesis, vitamin B conversion, immune function, and regenerate glutathione
• Creates precursors for nucleotides which are used to make nucleic acids for DNA and RNA

Glucose -> Glucose-6p -> Acetyl COA -> Citric Acid Cycle -> Electron Transport Chain

Glucose -> Glucose-6p -> Pentose Phosphate Pathway -> Ribose -> DNA, RNA -> NADPH -> Many functions

• Pathway is driven by insulin, which is produced in an energy rich state
• The generation of Ribose and NADPH are the critical molecules downstream
• Thiamine is a critical micronutrient to making the pathway run

What if we have enough ATP

• When intracellular energy stores are adequate, a feedback mechanism shuts down the generation of new ATP
• Extra glucose that is pulled out of the blood stream and into cells is then converted into a macromolecule called glycogen for long term storage
• The liver can hold ~75-100 grams of glycogen, and muscle can hold 300-400 grams

Glycogenesis is stimulated by high levels of Glucose-6P, and insulin As such, people with diabetes have poor glycogenesis/glycogen storage

What if Glycogen Stores are Full??

• When ATP builds up, citrate starts to build up in the cytosol

• This signals the cell to begin lipogenesis, or the process of making fatty acids for long term storage

excess acetylCOA builds up in a cell and needs to be stored as a fatty acid. this can’t just happen so Lipogenesis kicks off

Lipogenesis from Carbs

• Lipogenesis begins with one acetyl- CoA and continues by the continued addition of more acetyl-CoA molecules until an appropriate length fatty acid is formed
• This pathway can be used to make both triglycerides and phospholipids

Now we’re getting hungry again…Glycogenolysis

• Glycogenolysis is the breakdown of glycogen to produce glucose
  • Vit B6 dependent process
• This occurs a few hours into the fasted state, after which gluconeogenesis starts to takes over, created glucose from other fuel sources
• The liver can shuttle glucose out of the cell into the blood stream, the muscle cannot

Fed State - Carbs in Food

Fasted State Glycogen Stores -> Glucose (only about 10-18 hours of energy stores) Gluconeogensis - Amino Acids, Lactate, and Glycerol -> Glucose

Gluconeogenesis is glycolysis in reverse

Summary & Key Take Away Points

• Digestion breaks down macromolecules into molecules for absorption
• Glucose is then transported into cells through a number of transporters
• From there, it has a number of different fates • Aerobic metabolism to ATP
  • Anaerobic metabolism to lactate (most likely still we be used to generate ATP) • Storage as glycogen
  • Storage as a fatty acid
  • Conversion to ribose for nucleic acid synthesis
• Glucose can also be created by the body in the fasted state through gluconeogenesis
  • Amino acids, pyruvate, lactate and glycerol