Learning Objectives:
• Be able to identify the principal dietary carbohydrates and describe how they are digested and absorbed
• Be able to describe the processes of glycogen synthesis and degradation and understand how they are regulated
• Be able to describe the metabolic pathways of gl...
- when there’s plenty of
glucose in the cells its
stored as glycogen via
the process of
glycogenesis
- Releasing glycogen
from the store it can
be converted back to
glucose via the process
glycogenolysis when
there’s little glucose
- Process of ATP
production from
glucose breakdown is
glycolysis
- Spare energy resynthesize glucose – gluconeogenesis
Abbreviations
Why are carbohydrates metabolically important?
- Most cells can derive energy from three types of fuels: carbohydrates, amino acids and fatty
acids
- The major source of energy are the fatty acids which are degraded in mitochondria to acetyl-
CoA which enters the citric acid cycle
- Cells which do not possess mitochondria (red blood cells) or have relatively few (skeletal
muscle) either cannot, or have a reduced ability to, use fatty acids as fuels
- Citric acid cycle also requires oxygen – aerobic process needs oxygen rich tissues
- Cells with few mitochondria – need glucose as energy source as anaerobic process through
glycolysis doesn’t require oxygen and components located in cytoplasm
- The brain uses only glucose because fatty acids cant cross the blood-brain barrier
, - These cells rely on glucose as their source of energy
Dietary carbohydrate – digestion
- Approx. 300g of carbohydrate consumed per day. Most is starch
consisting of a mixture of amylose and amylopectin (plant
sources)
- Amylose – glucose molecules linked together in polysaccharide
chain linked by a α(1-4) glycosidic bond (Carbon 1 and carbon 4)
- Amylopectin – major component in starch glucose linked together
α(1-4) glycosidic bond and branch points α(1-6) bonds as well
- Form loose helical arrangements and are accessible for glucose
processing enzymes to bind
- Cellulous can’t be digested – not appropriate enzymes to
breakdown
- Digestion begins in the mouth with salivary amylase breaks down
α(1-4) bonds breakdown into disaccharides (2 glucose) maltose, trisaccharides (maltotriose)
or larger branched points (α-limit dextrins)
- Pancreatic juice contains two α-amylases to fully hydrolyse the bonds in the starch food
- Cells that line the small intestine (enterocytes) breakdown starch further into
monosaccharides. The maltose and maltotriose broken down by maltase. The branched
fragments are broken down further by α(1-6) glucosidase. The absorptive cells of the
intestinal villi secrete several CHO-degrading enzymes – α(1-6) glucosidase, maltase,
sucrose (breaks down fruit sugar and table sugar) and lactase (breaks down lactose)
Dietary carbohydrate – absorption
- The monosaccharides are absorbed into the body by the enterocytes (absorptive cells) of
the intestinal mucosa.
- Lumen of intestine lined with microvilli on the surface of this area the enterocytes which
produce a brush border. Maximises the surface area for uptake of molecules
- The monosaccharides are polar molecules because they have exposed hydroxyl groups they
are hydrophilic and so can’t be transported across the lipid bilayer by free diffusion but can
only by specific transport proteins (active transport) such as the
sodium-glucose linked transporter (SGLT1).
, - This transporter
means molecules
can enter the cells
against the
gradient. Need
energy for active transport which is
provided by setting up concentration
gradient of sodium ions across the membrane via a sodium-potassium exchange ATPase
pumps sodium out and brings potassium in. Hydrolysis of ATP provides energy for this.
- Lowering sodium in enterocytes ensures glucose uptake in cells. Influx of sodium ion down
concentration gradient to allow glucose to be absorbed via the co-transporter into the
enterocytes
- Once in the enterocytes the sugars need to cross the other membrane on the other side. On
the basolateral membrane this transport of sugar is facilitated diffusion (passive) down
concentration gradient. Transporter involved called GLUT2. Fructose can be taken up via
GLUT5 transporter then through GLUT2 into blood
The liver
- Absorbed sugars are passed to the capillaries of the villi and eventually join the bloodstream
in the hepatic portal vein which leads to the liver
- The liver is the first pass organ. It acts as a buffer for glucose and is the major organ for
controlling glucose homeostasis
- Takes glucose and stores it as glycogen in high glucose levels
Liver function
, - Glucose uptake into the liver cells (hepatocytes) is facilitated by GLUT2 (low affinity for
glucose) and is determined by the relative concentrations inside and outside the cells
- When blood glucose high there’s rapid transport into the liver through GLUT2, But when
blood glucose low, the low affinity of the GLUT2 means uptake is greatly reduced
- Within the hepatocytes glucose is phosphorylated by glucokinase which effectively traps the
glucose inside the cell. It can then be stored (as glycogen) or metabolised to produce ATP
(by glycolysis)
Glucose phosphorylation
- Glucose is phosphorylated to form glucose-6-phosphate by glucokinase enzyme for two
reasons:
1. To prevent it from passing out the cell: phosphorylation traps glucose in a cell because
GLUT2 can’t transport the phosphorylated form of glucose
2. To prepare it for storage by glycogenesis or breakdown by glycolysis: depends on energy
state of the cell and glucose availability
- Glucokinase has a low affinity for glucose but high capacity and high activity can process high
levels of glucose quickly, this enzyme specific to the liver
- Hexokinase used in other tissues and muscles
Regulation method 1: enzyme kinetics/isoenzymes
Isoenzymes:
- Isoenzymes differ in amino acid sequences but catalyse same chemical reaction , different
regulatory properties and different characteristics (hexokinase and glucokinase)
- Multiple forms of the same enzyme that catalyse the same chemical reaction
- They display different chemical and physical properties
- These different forms have different kinetic properties Glucokinase has low affinity for
glucose and high capacity whereas the hexokinase has a high affinity for glucose takes up
glucose more regularly but has a lower maximal activity so saturates at lower concentrations
- With hexokinase having a high affinity for glucose it can still take up glucose at lower levels
to generate glucose-6-phosphate but saturates at maximal rate at lower concentrations
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