GB 12. Post-Absorption Processing of Carbohydrates Flashcards
In the “fed” state what is the plasma levels of glucose, amino acids and triglycerides (chylomicrons)?
they are ALL increased
What are the control mechanisms (secretions) in the fed state? [2]
[1] increase secretion of insulin by pancreas
[2] decrease secretion of glucagon
What type of response does the body have in the fed state? (one word)
anabolic
- building big things from small things
What happens in the liver, adipose tissue, muscle and tissue in the fed state?
LIVER:
- makes glycogen, proteins + triglycerides (VLDL)
ADIPOSE TISSUE:
- makes triglycerides
MUSCLE:
- makes protein
TISSUE:
- uses glucose as “fuel”
In the “fasting” state what is the plasma levels of glucose, amino acids and triglycerides (chylomicrons)?
they are ALL decreased
What are the control mechanisms (secretions) in the fasting state? [2]
[1] decreased secretion of insulin
[2] increased secretion of glucagon + adrenaline
What type of response does the body have in the fed state? (one word)
catabolic
- the breakdown of larger molecules
What happens in the liver, adipose tissue, muscle and brain in the fed state?
LIVER:
- glycogenolysis
- gluconeogenesis
- beta oxidation
- ketogenesis
ADIPOSE TISSUE:
- lipolysis
MUSCLE:
- uses FAs + ketone bodies as “fuel”
- proteolysis supplies AAs to liver
BRAIN:
- uses glucose + ketone bodies as “fuel”
ketone bodies are transported from the liver to other tissues where they can be reconverted to acetyl coa
What are the 2 types of simple dietary carbohydrates? Give examples of each.
[1] monosaccharides
- glucose
- fructose
[2] disaccharides
- sucrose
- lactose
What are some examples of complex dietary carbohydrates?
- starch (plant sources)
- glycogen (animal)
- cellulose
What are the 2 overarching categories of dietary carbohydrates?
[1] Simple Carbs
[2] Complex Carbs
Where does absorption of carbohydrates mainly occur?
duodenum + upper jejunum
What are the enzymes involved in digesting carbohydrates in the gut?
[1] SALIVA
- contains Alpha-Amylase
- breaks down starch + glycogen
- however, pH restricted
[2] PANCREAS
- contans Pancreatic Alpha-Amylase
[3] GUT MUCOSA
- contains Oligosaccharidases + Disaccharidases (such as isomaltase, maltase, sucrase, lactase)
How long can liver glycogen support blood glucose levels for in the absence of food?
10 to 18 hours
What is gluconeogenesis?
synthesis of glucose from lactate, pyruvate, glycerol and so on
During over-night fasting, where does gluconeogenesis primary occur?
90% in the liver
10% in the kidneys
How does glucagon stimulate gluconeogenesis?
(normally stimultes glycogenolysis)
- glucagon opposes insulin and works to increase blood glucose levels
- it stimulates gluconeogenesis (which is increasing glucose blood levels)
List the 3 main substrates for gluconeogenesis.
[1] Lactate
- released into blood by exercising muscle
- gluconeogenesis in liver converts lactate to glucose
[2] Glycerol
- from fat stores (triglycerides)
[3] Amino Acids
- from tissue protein breakdown
What are the 3 irreversible reactions in glycolysis?
[1] Glucose to Glucose-6-Phosphate
[2] Fructose-6-Phosphate to Fructose-1,6-Bisphosphate
[3] Phosphoenolpyruvate to Pyruvate
What are the 4 special reactions that are used in gluconeogenesis to make glucose from pyruvate? (specific enzymes)?
[1] Pyruvate Carboxylase
[2] PEP Carboxykinase
[3] Fructose 1,6 Bisphosphatase
[4] Glucose-6-Phosphatase
- glucose-6-phosphate translocase
What is the structural unit of glycogen? Where are the main glycogen stores located? What is glycogen?
Structure: a polymer made of glucose (analagous to starch in plants)
Main Glycogen Stores:
- Liver: 10% by weight
- — used to maintain blood glucose
- Muscle: 1 to 2% by weight
- — used as a fuel reserve for ATP synthesis during muscle contraction
What is it?
- a rapidly mobilizable storage form of glucose
- when glycogen depleted, some tissues synthesize glucose via gluconeogenesis using amino acids
At what time of the day is the liver glycogen at its highest?
SLIDE 16 + 17**
What is the structure of glycogen?
- branched polymer of alpha-D-glucose units
- the chain is formed by alpha-1,4 glycosidic bonds
- the “branch points” are formed by alpha-1,6 glycosidic bonds
What enzymes (and protein) are involved in glycogen synthesis? (e.g. making the chain longer, creating the chain and making branches in the chain)
[1] Glycogen Synthase
- adds successive glucose units to the non reducing ends of growing chains, forming the alpha-1,4 bonds
- it can only make existing glycogen chains longer
[2] Glycogenin
- if there is no glycogen left, the protein Glycogenin acts as a primer accepting glucose units to form a new chain
[3] Branching Enzyme
- branches are made by this enzyme
- amylo-alpha (1-4) to alpha (1-6) transglucosidase
What is UDP-Glucose? What is the structure of UDP-Glucose?
UDP-Glucose: it is a precursor of glycogen
It has 2 parts:
- glucose
- uridine diphosphate
What enzymes are involved in glycogenolysis?
[1] Glycogen Phosphorylase
- cleaves alpha-1,4 glycosidic bonds
- cleaves successive glucose units off the chains (starting at non-reducing ends), then releases them as glucose-1-phosphate
- enzyme stops 4 glucose residues before each branch point
- —- this eventually produces a structure called a LIMIT DEXTRIN
[2] Debranching Enzyme
- branches are removed
[3] Phosphoglucomutase
- glucose-1-phosphate is then converted to glucose-6-phosphate
[4] Glucose-6-phosphatase (LIVER)
- converts glucose-6-phosphate to glucose for release into blood stream
[5] Glucose-6-Phosphate Translocase (LIVER)
- along with Glucose-6-Phosphatase to release free glucose from glucose-6-phosphate
then in MUSCLE, glucose-6-phosphate goes into glycolysis directly to produce energy
What is a limit dextrin?
after GLYCOGEN PHOSPHORYLASE cleaves the successive glucose units off of chain, they stop 4 glucose residues before each branch point…
- this produces the LIMIT DEXTRIN structure
What are the 2 key enzymes in the regulation of glycogen metabolism?
[1] Glycogen Synthase
[2] Glycogen Phosphorylase
What are the 2 levels of regulation in glycogen metabolism?
[1] Allosteric Regulation
[2] Hormonal Regulation
In the fed state, what happens to synthesis and degradation levels?
- increase synthesis
- decrease in degradation
In the fasting state, what happens to synthesis and degradation levels?
- decrease synthesis
- increase degradation
What are some examples of allosteric regulation in glycogen metabolism?
[1] Glucose-6-Phosphate*
- activates glycogen synthase
- inhibits glycogen phosphorylase
[2] Ca2+
- that is released by muscle during contraction, acts indirectly to activate Glycogen Phosphorylase
[3] High AMP
- in the muscle as a result of anoxia and ATP depletion, activates Glycogen Phosphorylase
How do hormones have a controlling effect on glycogen metabolism (general statement)? What mechanism do hormones use to control the activity of enzymes?
they act by controlling the activity of the enzymes
Mechanism: Reversible Phosphorylation/Dephosphorylation
- Protein Kinases = Phosphorylation
- Phosphatases = Dephosphorylation
Hormones (such as glucagon, insulin + adrenaline) act through this mechanism
How does phosphorylation and dephosphorylation affect both glycogen synthase and glycogen phosphorylase?
GLYCOGEN SYNTHASE:
- phosphorylated: less active
- dephosphorylated: active
GLYCOGEN PHOSPHORYLASE:
- phosphorylated: active
- dephosphorylated: less active
How does glucagon and adrenaline affect glycogen metabolism?
- they activate cAMP-dependent Protein Kinase A promoting phosphorylation
- net effect: glycogen breakdown
- glycogen synthase decreased
- glycogen phosphorylase increased
How does insulin affect glycogen metabolism?
- activates another protein kinase that causes dephosphorylation
- net effect: glycogen synthesis
- glycogen synthase increased
- glycogen phosphorylase decreased
Overall, in the FED state, insulin promotes…[2]
[1] glycogen synthesis
[2] triglyceride synthesis
Overall, in the FASTING state, glucagon and adrenaline promotes…[2]
[1] Glycogenolysis
[2] Lipolysis
What type of control is Adipose Tissue Lipase controlled by?
- it is hormone-sensitive
- controlled by phosphorylation and dephosphorylation
- it is ACTIVE, when PHOSPHORYLATED by PKA (lipolysis)
What are Glycogen Storage Disorder (GSDs)? What are they caused by?
- they are due to abnormal synthesis or degradation of glycogen
- due to a defect in the genes coding for enzymes involved in glycogen metabolism
What do GSD’s mainly affect? [2]
[1] liver
[2] muscle
- disease presentation + severity depend on the role played by the enzyme and its tissue specificity
What are the signs of Glycogen Storage Disorders (GSDs)?
- hypoglycaemia
- muscle pain
- muscle cramps
- weakness
What is another name for GSD V?
McArdle Disease
What is another name for McArdle Disease?
GSD V
What is another name for GSD I?
Von Gierke’s Disease
What is another name for Von Gierke’s Disease?
GSD I
What is the cause of GSD V and what happens?
- muscle glycogen phosphorylase deficiency
- muscle fatigue
- myoglobinuria
What is the cause of GSD I and what happens?
- glucose-6-phosphatase deficiency
- hypoglycaemia
- lactic acidosis (accumulation of glycolysis intermediates, phosphorylated glucose cannot leave the cell and is converted to lactate)
- ketosis
- hepatomegaly (accumulation of glycogen and fat)
What is the most common glycogen storage disorder? (accounts for 25% of all GSD cases)
GSD I (Von Gierke’s Disease)
