Carbohydrate metabolism Flashcards
What is the basis of metabolism
Making and using ATP by using ATP to drive reactions
How is energy for anabolic processed provided
The hydrolysis of ATP
How much ATP is present in tissues?
An amount only sufficient for a few seconds unless replenished
List the ways in which ATP can be replenished
Creatinine phosphate
- short term phosphate store
- used by muscle and nervous system
- Athletes can build up stores with supplements
Anaerobic metabolism of CHO to lactate
- all cells can do this
- produces some ATP
Aerobic metabolism of CHO, fat and/or protein
- Most cells do this the majority of the time
- requires mitochondria
- Majority of tissues use FA as substrate most of the time
List carbohydrates in the diet
Polysaccharides - chain of monosaccharides as a polymer - Starch - Cellulose Disaccharides - Maltose - glucose and maltose - Sucrose - glucose and glucose - Lactose - glucose and galactose Monosaccharides - Glucose - Fructose
Describe the carbohydrate structure of monosaccharides
All have the same chemical formula arranged in different ways (C6H12O6)
Can be recognised by different transporters
What is D-glucose?
Refers to the way solution of glucose will rotate plane of polarised light to the right (dextro)
What is L-glucose
laevo.
The mirror image enatiomer of D-glucose.
It is not found naturally
What is the difference between alpha and beta D-glucose
alpha-D-glucose has OH group below the C1 atom
beta-D-glucose has OH group above the C1 atom
Describe the structure of disaccharides
Disaccharides are linked by an alpha 1-2 glycosidic bond
Human enzymes can break these bonds
Describe the structure of polysaccharides
Polysaccharides are linked by an alpha 1-4 glycosidic bond
Where in the digestive tract can carbohydrates not be digested?
In the stomach, which only digests proteins
Which form of carbohydrates is mainly found in the diet?
Starch
What are dextrins?
Short chains of glucose, but does not qualify as starch
What does pancreatic enzymes break starch into?
dextrins and disaccharides
List 4 reasons some starches slowly digested compared to others?
1) Due to a structural cause
- trapped inside intact starch granules/plant cell wall structure (raw cereals, vegetables)
- Takes longer to liberate starch granules in this form
2) resistant to amylase
- 3D structure too tightly packed (processed foods, raw/cold potato)
- Tight packing causes smaller surface area for enzyme action = longer to digest
3) fibre increases viscosity, slowing down starch digestion
- associated with dietary fibre (slows absorption/digestion as gut contents becomes viscous (beans/legumes)
4) fat content
- CHO foods with high fat levels may have delayed gastric emptying
What is the glycaemic index
The glycaemic index (GI) is a rating system for foods containing carbohydrates.
What is the difference between high GI food and low GI food
High GI food = very rapidly absorbed (blood glucose shoots up)
Low GI foods = Take longer for the glucose to be liberated from the food, blood glucose goes up much less
How is cellulose digested?
Humans do not have the enzymes to cleave b-1,4 links of cellulose (polymer of glucose)
Cannot get calories from cellulose
Where is carbohydrates stored?
In the liver and skeletal muscle as glycogen
Muscle is the principle store.
Why is CHO homeostasis important?
Some tissues are dependent on the constant supply of glucose. A lot of energy is spent on this.
How does the brain use carbohydrates
Brain contains a lot of lipids and can make lipids but cannot take lipids out of the blood stream due to the architecture of the blood brain barrier
A lot of neurotransmitters are derived from glucose metabolites
How do erythrocytes use carbohydrates
Erythrocytes have no mitrochondria to oxidise glucose and can only carry out glycolysis
What is the normal blood glucose level
4-5mM (fasted)
In the brain it is slightly lower at 2-3mM
Levels can increase to 8-12mM after a meal
Some people are more CHO tolerant than others, and some have slower digestion/absorption
What are the principle regulators of glucose homeostasis?
The hormones insulin and glucagon.
Insulin = fed state
Glucagon = fasted state
How can glucose be synthesised?
De novo by the liver (and possibly kidney)
When asleep, glycogen reserves in the liver can maintain plasma glucose for 4-5 hours
Liver can then synthesise more glucose by gluconeogenesis to maintain plasma glucose
Kidneys can synthesise glucose during extreme starvation
How is glucose transported into cell?
By transporters as cannot simply diffuse in.
Either transported down conc. gradient by facilitated diffusion - GLUT1 - GLUT4
Or transported against conc. gradient using energy provided by co-transport of sodium (SGLUT1 and 2)
Where are SGLUT 1 and 2 normally found?
Required in the intestine to absorb from gut lumen and in the kidney to reabsorb from filtrate.
This system is crucial as you want to (re)absorb all the glucose, so at a certain point [glucose] will be higher in absorptive cells than in the lumen, as GLUT transporters will allow facillitated diffusion down the conc. gradient
GLUT 1
Present in all cells
Transports glucose and galactose
NOT fructose
GLUT 3
Predominantly found in neuronal tissues
Transports glucose and galactose
NOT fuctose
Found in brain, placenta and testes
GLUT 5
Fructose transporter only
Found in the gut, sperm and kidney as well
GLUT 2
Found in the liver and pancreatic beta cells, small intestine and kidney
Has a low affinity for glucose and acts as a glucose sensor
Liver and beta cells need to be able to sense blood glucose to secrete insulin/store glycogen
Transports glucose, galactose and fructose
High capacity glucose transporter
GLUT 4
Found on striated muscle (skeletal and cardiac) and adipocytes
Insulin-sensitive GLUT
More activity with higher insulin levels
High affinity for glucose
After a meal -> more glucose will be taken up into these tissues because of the insulin signal
SGLT-1/SGLT-2
Found in the intestinal mucosa, kidney tubules
Co-transport one molecule of glucose or galactose along with sodium ions.
Does not transport fructose
Describe how glucose is absorbed (intestine) or reabsorbed (kidney)
SGLT on apical membrane uses sodium gradient established by Na+/K-ATPase to absorb glucose
Normal GLUT system on basolateral membrane releases glucose into the capillaries
How do antidiabetic medications act on SGLT?
SGLT inhibitors.
More glucose is excreted, preventing hyperglycaemia
Describe GLUT 4 activity
insulin responsive (adipocytes and muscle only)
Insulin causes vesicles to translocate and fuse with cell membrane -> increased capacity for glucose transport due to increased number of transporters on the membrane
Physical activity also causes translocation of GLUT 4 in muscle (independent of insulin) ro provide more glucose for ATP production
In adipose and muscle, more glucose is transported when plasma glucose is raised after a meal - this is then converted to triglyceride of glycogen
What are pentoses used for?
DNA/RNA synthesis and ATP
5C sugars
Which form of glycogen cannot be broken down to plasma glucose?
Muscle glycogen.
It can only be used by the muscle itself for physical activity
Carb loading increases the time to fatigue
What are the sources of plasma glucose?
- Glucose from diet
- Glycogen from the liver (can be released back to the plasma glucose pool)
- gluconeogenesis (liver)
What are the uses of plasma glucose?
- Synthesis of pentoses
- Glycogen (muscle)
- Synthesis of fatty acid triglycerides
- Uptake by tissues
What is the fate of glucose within a cell?
- Production of ATP via glycolysis, TCA cycle and oxidative phosphorylation
- Storage as glycogen through glycogenesis
- Storage as lipid from acetyl CoA after glycolysis
- Synthesis of sugars for RNA/DNA through the pentose phosphate pathway
- Minor fraction is used to synthesse glycolipids & glycoproteins (ECM)
What is the first step of glucose pathways
Phosphorylation of glucose to glucose-6-phosphate
This traps glucose inside the cell so that it can no longer be transported out
Phosphorylation of glucose is catalysed by hexokinase I-IV
What determines the affinity of an enzyme for its substrate?
Km
Low Km = high affinity
High Km = low affinity
Describe properties of glucokinase
Hexokinase IV
- expressed by beta cells of pancreas and liver
- Has high Km (low affinity) -> acts as sensor
> Activity varies according to conc. of glucose due to reduced affinity
> Does not become saturates until very high levels f glucose are reached due to high Km
> Don’t want liver to pick up glucose and store it unless plenty is available
- regulated by enzyme synthesis
- not inhibited by G6P -> Allows accumulation in the liver for storage as glycogen
Describe the properties of hexokinase I-III
- Expressed in all other tissues
- Has low Km (high affinity) for glucose
> Can efficiently use low levels of glucose
> Quickly saturated
> Km is lower in skeletal muscle (and most other cells), which has GLUT-4, which allows muscles to grab up the glucose much more avidly - is inhibited by G6P (feedback inhibition)
Describe the kinetics of Hexokinase I-III
Have a very high affinity for glucose
Activated at low levels of glucose and are quickly saturated
Describe the kinetics of glucokinase
Only activated at higher levels of glucose
> Rate of G6P production will not change its activity (no feedback inhibition)
> Liver uses it as a signal for glycogen storage
Beta cells use this as a signal for insulin release
Describe glycolysis
Breakdown of glucose to yield ATP
Occurs in the cytoplasm of all cells
Glucose + 2ADP + 2Pi + 2NAD+ => 2 Pyruvate + 2 ATP + 2 NADH + 4H+
Initial stages use 2 ATP
What is the function of phosphofructokinase?
Catalyses the committed step of glycolysis
Activity determines whether G6P from hexokinase/glucokinase used for glycolysis or other purposes
Inhibited by ATP, citrate (downstream products), which serves as a form of regulation
What is the function of pyruvate kinase
Catalyses the final step of glycolysis
What is the end product of glycolysis
Pyruvate
What is the initial output and end yield in glycolysis
glycolysis uses 2 ATP and generates 4ATP and 2NADH
What is the purpose of NADH
To be used to replenish NAD+, which has only a limited pool
- Under anaerobic conditions -> lactate formation (no further ATP is produced)
- Under aerobic conditions -> NADH can be used to make more ATP in the mitochondria
How is fructose broken down?
Fructose is converted to fructose-1-phosphate (F1P) by fructokinase
F1P is converted into intermediates of glycolysis
How does fructose link to glycolysis
Fructose feeds in lower down in glycolysis
This means it is not regulated by two key steps
High fructose diet can have a huge impact on metabolism -> more likely to lay down lipids
What is the fate of galactose?
Galactose is converted to glucose-1-phosphate, then G6P by a number of steps
What are the fates of pyruvate?
Lactate (anaerobic conditions)
Anaerobic conditions: pyruvate -> acetyl-CoA
> occurs in the mitochondria
> produces c02 and NADH + H+ aerobic acetyl-CoA used in the TCA cycle
How is lactate produced?
pyruvate is converted to lactate using NADH
Therefore 2 ATP from every molecule of glucose
Lactate dehydrogenase as catalyst
How is acetyl CoA produced?
Pyruvate is converted to acetyl CoA with pyruvate dehydrogenase as a catalyst
Requires vitamins as co-factors (thiamine, niacin, riboflavin)
What does CoA mean?
Coenzyme (lots of vitamins)
Cannot be synthesised but is required for metabolism
Describe the Krebs cycle
8 reactions
mitochondrial
hub of cellular metabolism
intermeditates are precursors for the biosynthesis of other compounds
Describe ATP production from precursors
Every NADH molecule can produce 3 ATP
Every FADH2 molecule can produce 2 ATP
Every GTP molecule can produce 1 ATP
