Biochemistry- carbohydrate metabolism Flashcards
What are the methods of carbohydrate uptake in the diet
Carbohydrates are the major macronutrient in most human diets.
Efficient uptake of digested sugars is important, and the epithelial cells lining the digestive tract may employ a number of
transporters to make sure that glucose molecules are not left behind:
o Primary active transport: used to establish a concentration gradient that can be used to bring in glucose.
o Secondary active transport: used to couple the transport of glucose to the transport of sodium down its
electrochemical gradient. Using an existing concentration gradient to pull another substance across.
o Passive transport: allows the glucose to leave the epithelial cell and enter the blood, down its concentration gradient
How does glucose uptake occur
Glucose is absorbed into enterocytes using the free energy of the sodium
gradient.
Glucose uniporter GLUT2: facilitates the efflux of glucose from the cell to the
blood across the basal surface of the enterocyte.
The Na+/K+ ATPase on the basal side of the enterocyte uses the energy of ATP
hydrolysis to decrease [Na+] within the cell.
This maintains the downhill Na +
gradient between the lumen of the intestine and the cytosol of the enterocyte.
Describe glycaemic index
A measure of the effect of ingesting a standard amount of carbohydrate (e.g. 50 g) on blood glucose compared with the
same amount of glucose. Measured by the area under the graph.
Crystallised starches or those associated with hydrophobic proteins are resistant to hydrolisation. Therefore have a low
glycaemia index (e.g. raw potatoes).
Food processing often makes starches more available to the soluble amylases, increasing the glycaemic index.
Low GI/GL diets have been associated with several benefits:
o Decreased in serum C-reactive protein
o Decrease in glycation of proteins
o Reduced LDL and higher HDL
o Decreased food intake in subsequent meal
People suffering from insulin resistance may benefit more from low GI diets.
Populations that have traditionally used a low GI food as a staple and have recently moved to more modern diets are now
experiencing high rates of diabetes (e.g. Pima Indians, Australian aborigines).
What is the glucose tolerance test and what values indicate diabetes/impaired glucose tolerance?
Tests the response to a glucose load, typically 75g for an adult, over a period of
time.
The test is performed at 10 in the morning, after a 10 hour fast.
The test can be affected by recent illnesses and exercise, so the patient must
remain seated.
At 120 mins, if the sample is > 11.1 mM, the patient is considered to have diabetes.
Normal fasting glucose and 120 min levels between 6.1 and 7.8 mM may indicate
impaired glucose tolerance.
What are the effects of htyperglycaemia on the body
Glucose can non-enzymatically glycated Lys and Val residues, altering protein activity (e.g. glycation of apolipoprotein B,
altering cholesterol metabolism).
The glycated proteins undergo further reactions, forming advanced glycation endproducts (AGEs).
AGE accumulation is involved in the pathogenesis of many age-related diseases (e.g. CVD) but occurs faster in
hyperglycaemia.
Aldose reductase has a high Km for glucose, so in insulin-independent tissues, at high levels, glucose is converted to
sorbitol. Sorbitol interferes with osmotic pressure in ocular tissue and nerve function in nerve cells.
How do you test for glycated haemoglobin
The glycation reaction is irreversible, so the percentage of haemoglobin that is glycated (HbA1C) can give a good indication
of average glycaemia in a patient. Normal [HbA1C] is 4-6%.
Testing the [glucose] in blood and urine only tells about the current time.
Testing for glycated haemoglobin is useful in identifying patients who are not following the dietary advice, or are missing
insulin injections.
Describe Type 1 diabetes
Caused by autoimmune destruction of the pancreatic β cells, destroying their ability to secrete insulin and respond to
ingested carbohydrate appropriately.
Typically develops in the young (peak age 12).
Susceptibility is inherited via the genes of the major histocompatibility complex.
Must be treated with insulin injections.
Untreated individuals will develop hyperglycaemia and ketoacidosis and do not survive for long.
Describe type 2 diabetes
Usually develops in obese patients over 40 years old, caused by a combination of insulin resistance and impaired insulin
secretion.
Susceptibility is inherited, as seen by the increase risk for those with diabetic relatives (especially twins).
Develops over a period of time. Obesity is associated with insulin resistance, hyperinsulinaemia, followed by glucose
intolerance.
Improved diet (even if weight remains the same) and exercise can slow down the process or even reverse it.
Treatment involves lifestyle changes, and may involve insulin injections (less common), drugs that increase insulin secretion,
or that increase insulin sensitivity.
Describe the response of GLUT 4 to insulin
Insulin released in response to the increase in plasma glucose levels acts to increase the uptake and metabolism of glucose.
The presence of the GLUT4 isoform confers insulin sensitivity, as it
translocates to the membrane in response to insulin, allowing the cell
to take up glucose.
It is most important in muscle and adipose tissue.
It is not found in the brain or liver.
Low insulin concentration (e.g. fasting): GLUT4 are arranged on a
vesicle inside of the cell.
High insulin concentration (e.g. fed): GLUT4 are arranged on the cell
membrane to allow the transport of glucose across the membrane.
What are the metabolic fates of glucose in skeletal muscle, adipose tissue and the liver?
Tissues increasing glucose uptake in the fed state may use it for different purposes.
Skeletal muscle: increase the rate of glycolysis, decrease fatty acid use and convert some glucose into glycogen. Helps to
decrease [glucose] in the blood.
Adipose: use excess glucose for fatty acid and triacylglycerol synthesis. Triacylglycerol is lighter and more compact than
glycogen (better storage).
Liver: increase rate of glycolysis and decrease fatty acid use and convert some glucose into glycogen. Extra glucose can be
used for fatty acid synthesis and triacylglycerol synthesis.
Why is glycogen used as a store
Relative to an equivalent amount of glucose, glycogen puts much less osmotic pressure on the cell.
Glycogen takes up more space, weighs more and stores less energy than triacylglycerol. The body is also capable of storing
only a limited amount (450 g, enough to last less than a day).
Unlike triacylglycerol, glycogen is a store of glucose (the fatty acids in triacylglycerol cannot be converted into glucose).
Some tissues rely on glucose as a source of fuel, most notably the brain, and cannot use fatty acids.
So even though triacylglycerol is a more compact, energy dense store of fuel, and can be stored in potentially unlimited
amounts, glycogen is necessary as a store of glucose, rather than simply fuel.
Describe the structure of glycogen
Approximately 13,000 glucose units in a 30 nm sphere.
The chains are formed by α(1,4) glycosidic linkages, branching off at α(1,6) linkages which are 8-10 glucose long.
The branching structure of glycogen increases its solubility, making it more accessible to enzymes.
Branching also increases the number of glucosyl residues that can be removed (or sites where glucose can be added),
thereby increasing the potential rate of glycogenolysis (or glycogenesis).
Describe the steps in glycogenesis
- Glucose activation
Phosphoglucomutase converts glucose-6-phosphate to glucose-1-
phosphate.
UDP-glucose pyrophosphorylase adds UDP to form uridine
diphosphate glucose.
Molecules recgonise glucose and the UDP residue. - Chain elongation
Glycogen synthase requires a primer of at least four residues. It is
a key point of regulation in glycogenesis.
The glycogen dimer is an autocatalytic glucosyltransferase. Each
subunit catalyses the addition of 8 glucose molecules (from UDPglucose) to the other subunit. - Chain elongation
Glycogen synthase catalyses the addition of a uridine diphosphate
glucose to a growing glucose chain. It cannot work on a chain
shorter than 4 glucose residues. - Branching
To create a new branch point, branching enzyme takes the last
7 residues from a non-reducing end and adds it to the growing
end of the glucose chain to form 2 branching points which are
more than 4 residues long.
Describe 2 glycogen storage diseases
1. Glycogen synthase deficiency (GSD-0) Poor tolerance of fasting (drowsiness, hypoglycaemia) (low glycogen levels) Postprandial hyperglycaemia A need for frequent snacking Tires easily during exercise
- Glycogen branching enzyme deficiency (GSD-IV, Andersen’s disease)
Accumulation of unbranched, insoluble glycogen chains (polyglucosan) (especially in the heart and liver).
Causes liver cirrhosis.
Briefly describe glycolysis
Glycolysis is the first stage in the breakdown of glucose.
It requires no oxygen and occurs in the cytosol (the only ATP producing
pathway that does not require mitochondria).
The pyruvate produced can be further oxidised, or converted into other
compounds.
