carbohydrate metabolism Flashcards
ATP
- adenosine triphosphate
- energy fro anabolic precesses is provided by the hydrolysis of ATP
ATP+ energy liberation= ADP + Pi
ADP + Pi + atp resynthesis= ATP
replenishing ATP
– creatine phosphate (muscle – short term)
– anaerobic metabolism of CHO to lactate
-aerobic metabolism of CHO, fat and/or protein ( in mitochondria)
tissue dependent on glucose
- erythrocytes: no mitochondria, therefore cannot oxidise fuels, only ATP from glycolysis
- brain: fatty acids cannot cross blood- brain barrier
- rate of tap production from fatty acids is too slow/requires too much oxygen
carbs in diet
- polysacchrides: starch nd cellulose
- dissacharides: maltose, sucrose, lactose
- monosaccharides: glucose and fructose
digestion of carbs
Digestibility of starch varies with properties of food
Some starches slowly digested
*trapped in intact starch granules/plant cell wall structure
(e.g. raw cereals, vegetables)
*resistant to amylase as 3D structure too tightly packed
(some processed foods, raw/cold potato)
*associated with dietary fibre - slows absorption/digestion as increases gut content viscosity (e.g. beans/legumes)
- CHO foods containing high levels of fat may have delayed gastric emptying
carbs homeostasis
- Glucose is transport from of CHO in humans Glycogen is storage form of CHO in humans
- Some tissues, including the brain and erythrocytes are dependent on the constant supply of glucose
- Plasma glucose concentration is tightly regulated and maintained between
concentrations of 4-5 mM (in fasted state). Can raise to 8-12 mM after a meal. - The principal regulator of glucose homeostasis are the hormones insulin and glucagon
- glucose can be synthesised de novo by the liver or kidney to plasma glucose
glucose transport into tissues
-* Glucose transport into cells requires transporter proteins. Cannot simply diffuse into cells.
*Transported down concentration gradient by facilitated diffusion – GLUT1- GLUT14. (GLUT1-5 well-characterised)
*Transported against concentration gradient using energy provided by
cotransport of sodium (SGLT1 and 2). Required in intestine to absorb from gut lumen and kidney, to reabsorb from filtrate.
glucose transporters, SGLT-1/SGLT-2
site- intestinal mucosa, kidney tubules
characteristics- Co-transport one molecule of glucose or galactose along with sodium ions. Do not transport fructose.
glucose transporters, GLUT-1
site- ubiquitous
characteristics- Transports glucose (high affinity) and galactose, not
fructose.
GLUT-2
site- liver, small intestine, kidney
characteristics- Transports glucose, galactose and fructose. A low
affinity, high capacity glucose transporter
GLUT-3
site- brain, placenta and testes
characteristics- Transports glucose (high affinity) and galactose, not
fructose. The primary glucose transporter for
neurons.
GLUT-4
site- skeletal and cardiac muscle, adipocytes
characteristics- The insulin-responsive glucose transporter. High
affinity for glucose.
GLUT-5
site- small intestine, sperm
characteristics- transports fructose, but not glucose or galactose
insulin responsive GLUT-4
-Found in adipose & muscle, therefore, more glucose transported in (& converted to triglyceride or glycogen) when plasma [glucose] is raised after a meal because of increases insulin
- In muscle, GLUT4 translocates in response to physical activity/exercise (independent of insulin) therefore, more glucose used for ATP production
fate of glucose within a cell
- production of ATP: * Glycolysis *TCA cycle & Oxidative Phosphorylation
- storage as glycogen: glycogenesis
- synthesis of sugars for RNA/DNA: pentose phosphate pathway
- synthesis of other molecules: synthesis of triglycerides (lipogenesis), some amino
acids, neurotransmitters etc.
phosphorylation of glucose
- All pathways require phosphorylation of glucose to glucose-6-
phosphate as first step - Phosphorylation traps glucose inside the cell, cannot be transported out.
Phosphorylation of glucose catalysed by hexokinases I-IV
hexokinases I-IV
- glucokinase (hexokinase IV) expressed by cells of pancreas and liver –has high KM
–Enzyme synthesis regulated
hexokinase I-III
–expressed in all other tissues
–has low KM
–is inhibited by G6P (feedback inhibition)
glycolysis
- breakdown of glucose to yield energy
- occurs in cytoplasm of all cells
Glucose + 2ADP + 2P+ 2NAD+
into
2 Pyruvate + 2ATP + 2NADH + 4H+
glucose to glucose-6-phosphate
ATP into ADP
hexokinase/glucokinase
glucose-6-phospahte to fructose-6-phosphate
- phosphoglucose isomerase
fructose-6-phosphate to fructose-1,6- bisphosphate
ATP- ADP
phosphofructokinase-1
phosphofructokinase (PFK)
- inhibited by ATP, citrate, downstream products
- activity determines wether G6P from hexokinase/glucokinase used for glycolysis or other purposes
glycolysis net gains and uses
Uses 2ATP and generates 4ATP and 2NADH
- Net gain of 2ATP and 2NADH
- Phosphofructokinase is the committed step for glycolysis
- Under anaerobic conditions get lactate formation (no
further ATP produced - Under aerobic conditions, NADH can be used to make more ATP in mitochondria
fructose and galactose
fructose: converted to Fructose-1-phosphate (F1P) by fructokinase *F1P is converted into DHAP and Glyceraldehyde-3- phosphate
*DHAP and Glyceraldehyde 3-phosphate are intermediates of glycolysis
galactose: converted to Fructose-1-phosphate (F1P) by fructokinase *F1P is converted into DHAP and Glyceraldehyde-3- phosphate
*DHAP and Glyceraldehyde 3-phosphate are intermediates of glycolysis
fates of pyruvate
- lactate (anaerobic conditions)
- pyruvate —> acetyl CoA
- occurs in mitochondria by pyruvate dehydrogenase
- Produce CO2 and NADH + H+
Aerobic
Acetyl-CoA can be used in the TCA cycle
lactate production
pyruvate into lactate
NADH-NAD
by lactate dehydrogenase
- 2 ATP from every glucose
citric acid cycle
TCA/KREBS
3 NAD+ + FAD + GDP + Pi +acetyl-CoA
into
3 NADH + FADH2 + GTP + CoA + 2 CO2
pentose phosphate pathway
importnat for synthesis:
- NADPH
- required for generation of lipids by reductive biosynthesis
- required for reduction of glutathione (antioxidant)
- ribose 5-phosphate, formation of nucleotides (DNA/RNA)
- dehydrogenation of glucose 6-phosphate is the committed step
glycogen
-synthesized from glucose
- liver: storage fro blood glucose maintenance
- muscle: storage for local energy production (only used by muscle itself)
hormonal regulation of glycogen synthesis
- glucagon (liver) and (nor) adrenaline (liver and muscles)
–Increase glycogen phosphorylase activity rapidly
–Inhibit glycogen synthase activity rapidly
-insulin (liver and muscle)
–Increase glycogen synthase activity rapidly
–Inhibit glycogen phosphorylase activity rapidly
gluconeogenesis
- the synthesis of glucose from a noncarbohydrate (nonhexose) source.
–Lactate
–Pyruvate
–Glycerol
–Certain amino acids
gluconeogenesis in liver
- occurs mainly in the liver
- kidneys can contribute with prolonged starvation
- essentially a reversal of glycolysis ( hexokinase/glucokinase, PFK, pyruvate kinase not reversible)
glucose 6-phosphatase
- only expressed at high levels in liver
- therefore, only liver can convert glucose-6-phosphate back into glucose
- glucose can then be transported by GLUT2 out of hepatocyte into the blood
- allows maintenance of blood glucose levels in the fasted state
substrates for glycogenesis
lactate: converted to pyruvate first
glycerol: converted to DHAP (dihydroxyacetone phosphate), intermediate in glycolysis
amino acids- converted into pyruvate or various in TCA cycle intermediates
