Carbohydrate Metabolism and dietary handling

Question 1

What are the 5 portions of metabolism of carbohydrates?

Answer 1

• Glycolysis
  
  • TCA cycle
  • Gluconeogenesis
  • Glycogen synthesis and breakdown
  • Pentose Phosphate Pathway

Question 2

What is oxidation?

Answer 2

• Transfer of electrons from a reduced molecult ot an acceptor molecule
  
  • The acceptor molecule gains the electron and becomes reduced
  • Donor molecule loses an electron and becomes oxidized

Question 3

What is the Km?

Answer 3

• The concentration at which the reaction is half maximal is the Km
  
  • If a reaction has a low Km it suggests that the substrates have a strong affinity for the enzyme and the reaction will go at low substrate concentrations

Question 4

What is Vmax?

Answer 4

• Maximal rate

* High Vmax means there will be a ton of product in a short period of time

Question 5

Why is conversion of glucose to G6P a key step in glycolysis?

Answer 5

• This traps the glucose inside the cytoplasm

* It’s also an ATP investment step

Question 6

What is the rate-limiting step in glycolysis?

Answer 6

• The conversion of fructose 6P to fructose-1,6-bis-P is rate-limiting and very important
  
  • The bottleneck of glycolysis
  • Performed by PFK1
  • Second investment of ATP step

Question 7

Pyruvate is important why?

Answer 7

• Energy source for other pathways after glycolysis
• This is the end-result of glycolysis
• With oxygen and mitochondria, TCA cycle and electron transport
• It can also be put into formation of fatty acids
*when no mitochondria like in sperm and RBCs, conversion to lactate and export form the cell helps regenerate the NAD from NADH to allow glycolysis to continue (since this reaction by itself can produce some ATP)

Question 8

NADH and FADH2 are important for what cycle?

Answer 8

• Electron transport chain

Question 9

What is the overall goal of TCA cycle?

Answer 9

• Acetyl-CoA to CO2 w ith the release of a good deal of energy stored in GTP, NADH and FADH2

Question 10

What is nice about the variety and flexibility in the carbon skeletons being used in the TCA cycle?

Answer 10

• You can get, in times of excess, acetyl-coa that goes in but gets kicked out for other reactions like the synthesis of fatty acids

Question 11

What is the electron transport system?

Answer 11

• The inner membrane of the mitochondria

* NADH and FADH2 must get into the mitochondria to participate in the electron tansport chain

Question 12

What’s up with gluconeogenesis?

Answer 12

• Glucose for the brain is super important
• In fasting state the liver and kidney produce glucose
• Sources for carbon in this processare typically lactate, amino acids from muscle, or glycerol from triglyceride breakdown in adipose tissue
• These substrates are transported through the blood stream to the liver where they are converted to glucose (gluconeogenesis)
• Amino acis must first lose nitrogen (urea cycle)
• Essentially gluconeogenesis is glycolysis in reverse but it uses different enzymes
○ These enzymes are regulated in the reverse manner
• Also, this uses energy, it doesn’t create energy
• THREE KEY REGULATED STEPS here
○ Same as in glycolysis
• First - conversion of pyruvate to phosphoenol pyruvate
○ Through oxaloacetate and malate and is catalyzed by pyruvate carboxylase and phospho-enol-pyruvate carboxy-kinase (PEPCK)
○ Second - producto of F6P from F16BP
§ By F16bisphosphatase

Question 13

What’s up with glycogen?

Answer 13

• Rapidly available source of glucose for acute energy needs
  
  • Stored within tissues, though only liver stores are available for direct brain use
  • Synthesized from glucose-6-P
  • Important hub in glucose metabolism because it either goes down glycolysis pathway or gets stored as glycogen
  • First step is conversion of G6P to glucose-1-P then converting glucose-1-P to UDP-glucose
  • Committed step in synthesis of glycogen thus KEY
  • Second key step is catalyzed by the enzyme glycogen synthase which adds UDP-glucose to growing glycogen molecule
  • Glycogen phosphorylase is the enzyme that removes glucose from glycogen and another key enzyme highly regulated
  • Once activated, glycogen is made by glucose being added in a 1-4 orientation
  • Highly brached polymer for the rapid release of many glucose molecules at a time
  • Super important for STEP as inborn glycogen storage diseases result in poor release and poor storage of glucose
  • Glycogen breakdown is from the ends until a branch-point is reached then another enzyme takes off the branch point

Question 14

Describe in general the pentose phosphate pathway

Answer 14

• AKA hexose monophosphate shunt
• Modest amount of lgucose in the liver glycolysis is the preferred pathway
• When more glucose is available, glycogen storage becomes a site for glucose disposal
• When glucose is abundant, directed to pentose phosphate pathway with two main functions
○ Generation of NADPH, the source of energy for synthesis reactions
§ Fatty acid, cholesterol, defense against oxidative stress, WBC function
○ Generation of five cabon sugars for nucleotide synthesis
• KEY STEP = oxidation of glucose-6-phosphate to 6-phosphogluconolactone
○ By G6PD
○ Glucose-6-phosphate dehydrogenase

Question 15

Insulin is balanced by counter-regulatory hormones. What are these?

Answer 15

• Glucagon
	• Catecholamines
	• Growth hormone
	• Cortisol
		○ In particular, catecholamines and glucagon bind to membrane associated receptors that alter intracellular signaling pathways typically by changing the levels of cAMP and kinases that phosphorylate key enzymes in tehse pathways in a manner that alters activities

Question 16

What’s going on in an insulin-high state?

Answer 16

• Fed state
  
  • Insulin high, counter-regulatory hormones like glucagon low
  • Glycolysis and glycogen synthesis are active and glucose is assimilated by peripheral tissues
  • Gluconeogenesis and glycogen breakdown reduced

Question 17

How might you go from energy expenditure to what the estimated energy from carbs a person eats?

Answer 17

• In energy balance (weight neutral person) then EI is equal to EE
• Thus, use the formula tot get to EE and figure out the percentage of carbs a person ate
• 70kg man, diet containing 15% protein, 35% fat, 50% carbohydrate
○ Number of grams of carbs consumed per day is 2100*0.5=1050
○ 1050/4=262.5 grams of carbs
• Carbohydrate counting in diabetes refers to the practice of estimating the grams of carbohydrate in a meal and adjusting the dose of insulin administered to cover or correct that dose of carbs

Question 18

A super rough, average estimate of a normal persons energy expenditure is what?

Answer 18

• EE = energy expenditure
• Rought estimate is that EE = 25-35kcal/kg per day
○ Depending on levels of physical activity
• 70kg person, normal activity, assume 30 kcal/kg so a total EE of 2100 kcal/day

Question 19

What are the average energy densities of each macronutrient?

Answer 19

• Carb = 4 kcal/g
  
  • Protein = 4kcal/g
  • Fat = 9 kcal/g
  • Alcohol = 7 kcal/g

Question 20

Describe where most of the energy intake, used to match the energy expenditure in a weight staple person, comes from

Answer 20

• Most of the energy content of the diet comes from 3 macronutrients of carbohydrate, protein and fat
• Essentially, EI will be the sum of the macronutrients
○ Don’t forget alcohol can contribute quite a bit too
• Protein intake is generally 15-20% of calories
• Fat and carbohydrate together accound for about 80% (remainder)
○ 25-25% fat and 45-60% carbohydrate

Question 21

Sucrose and lactose are examples of what type of carbohydrate?

Answer 21

• Disaccharides, labeled as sugars

Question 22

What are the polysaccharides to recognize by sight?

Answer 22

• Polysaccharides are over 9 sugars long
  
  • Amyolse and amlyopectin = starch
  • Cellulose, hemicellulose and pectins are FIBER

Question 23

What are the oligosaccharides to recognize by sight?

Answer 23

• Maltodextrins
  
  • Raffinose
  • Stachyose

Question 24

What are the sugar alcohols?

Answer 24

• Sorbitol
	• Mannitol
	• Xylitol
	• Hydrogenated starch hydrolysates
		○ These are labeled on food items as sugar alcohols

Question 25

A high glycemic index vs. a low glycemic index means what?

Answer 25

• Low GI = a carbohydrate form that results in less glucose and less insulin in the blood
  
  • High GI = high excursion of glucose and insulin in the blood

Question 26

What are some examples of low to intermediate glycemic index foods?

Answer 26

• Low gi foods
		○ Range below 55
		○ Sourdough bread
		○ Apple juice
		○ Pumpernickel
		○ Oatmeal
		○ Pasta
	• Intermediate
		○ Croissant
		○ Coca-cola
		○ Raisin bran
		○ Whole grain bread
	• High gi foods
		○ Range Above 70
		○ White bread 
		○ Corn flakes
		○ Doughnut
		○ White rice

Question 27

What numbers do you need to figure out the glycemic load of a given food?

Answer 27

• The GI or glycemic index multiplied by the percentage of carbohydrate in the food item
  
  • You need the percentage of carbohydrate
  • You need the GI of the food
  • The multiplied value of these two is the glycemic load

Question 28

What are the differences in fructose metabolism compared to glucose metabolism?

Answer 28

• Enters cells through general hexose transporter and so its entrance is not regulated by insulin
  
  • It does not stimulate insulin release
  • It does not enter glycolysis at fructose 1,6 bisphosphate because hexokinase is typically completely used to metabolize glucose
  • Instread, fructose is typically phosphorylated by fructokinase in the liver which produces fructose 1-phosphate
  • It is then phosphorylated at the 6 position and converted by the action of aldolase into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate entering glycolysis at a step which effectively bypasses the key regulated step of PFK
  • Thus, fructose much more readily is cleared by the liver and in the liver readily converted to pyruvate bypassing much of the regulated portion of glycolysis
  • Think of it like a super glucose and it may explain the adverse health effects of high fructose diets

Question 29

Fructose will enter the glycolysis pathway, but will it enter up at the top and join the regulated species like glucose?

Answer 29

No, it only enters at the level of glyceraldehyde-3-P, which is much further down the pathway.
*essentially, fructose is much more quickly cleared by the liver because it is shoved super fast down the glycolysis pathway bypassing the KEY REGULATORY STEP of PFK1 phosphorylation.

Question 30

Where does lactose end up in digestion?

Answer 30

• Lactose is a disaccharide of glucose and galactose
  
  • Galactose is metabolized by galactokinase to produce UDP galactose
  • This is important in the production of glycolipids and glycoproteins
  • OR it can be converted to UDP glucose for the purpose of glycogen storage or breakdown
  • Think of glucose from galactose entering carbohydrate handling in the glycogen storage and breakdown “arm”

Question 31

Describe in general what happens in oligosaccharide digestion

Answer 31

• Short chain polysaccharides
  
  • Found in beans, onions, asparagus and other vegatables and probiotics like yogurt
  • Incompletely absorbed and thus contribute mainly to colonic fermentation
  • Colonic fermentation produces short chain fatty acids that are BENEFICIAL for insulin sensitivity and lipid levels
  • Fermentation does produce gas and bloating though, so some people don’t love these effects or these foods

Question 32

What kind of starch is amylopectin? How is it digested?

Answer 32

• Highly branched polysaccharide of glucose
  
  • Intestinal amylase as many free ends of the polymer to digest
  • Amylopectin has rapid absorption
  • White bread, potatoes and many pastas
  • High GI of these foods because of rapid absorption

Question 33

What kind of starch is amylose and how is it digested?

Answer 33

• As opposed to amylopectin, amylose is a long straight (unbranched) chain of glucose
  
  • Not as quickly absorbed because amylase needs free ends to chew
  • Basmati rice and bananas
  • Can result in the same colonic fermentation that is good, but gives gas

Question 34

What is meant by “resistant” starch?

Answer 34

• Corn starch is the classic example
  
  • Because of its crystal structure it is slowly absorbed
  • Simply a matter of preparation causes the different absorption rate since it has the same source as amylopectin, which is rapidly absorbed
  • Used in children with inborn errors of metabolism that predispose them to hypoglycemia due to problems with hepatic glucose production during fasting

Question 35

What is dietary fiber?

Answer 35

• Complex carbohydrate that is not digestible by human intestinal enzymes
• They pass through the GI tract largely unaltered
• Increase stool volume and may lower serum cholesterol levels
• Husk of grains, oats, vegetables and fruits
• Broken into insoluble vs. soluble fiber
• Insoluble - does not absorb much water
○ Celery, whole wheat, bran
• Soluble - absorbs water, kind of like a bulk forming laxative
○ Lower LDL cholesterol levles
○ Lower post-prandial glucose excursions
○ Guar gum
○ Psyllium
○ Beta-glucan
○ Beans, oats, barley, apples, frutis

Question 36

If you wanted to study the interplay of a given dietary factor in the development of diabetes, how might you decide your research end-points?

Answer 36

• Usually focus on insulin sensitivity
• Fasting levels of insulin and glucose
• Calculated values of insulin action derived from fasting insulin and glucose
○ HOMA
○ QUICKI
• Frequently sampled IV glucose tolerance test
○ FSIGTT
○ Bolus of glucose is injected into a person IV and blood glucose and insulin are mesured over time
• Euglycemic hyperinsulinemic clamp
○ Insulin is infused at a constant rate and glucose is infused at a variable rate to maintain a stable blood glucose level
• Large range in accuracy and ease of implementation, so use different ones for different sizes of study