Carb Metabolism Flashcards
(78 cards)
Key Reactions, Enzymes and Transport Proteins in Carb Digestion/absorption
Saliva (salivary amylase - breaks alpha 1,4 glucosidic bonds) —> 2 phases in SI (see below) —> absorbed at brush border (GLUT5 and SGLT1) —> exit basolateral membrane into portal circulation (GLUT 2)
2 Phases of Carb Digestion (+ where each occurs)
- Pancreatic Phase- LUMEN
- Secretin- stim release of pancreatic juice w/ bicarb to neutralize stomach chyme
- CCK- stim release of pancreatic alpha-amylase
- Products = maltose, glucose and limit dextrins (glucose still connected by alpha 1,6 bonds)
- Disaccharide phase - BRUSH BORDER
- DIsaccharidases (maltase, lactase, isomaltase/sucrase double-headed enzyme)
- Dextrinase cleaves alpha 1,6 bonds in limit dextrins
Glucose Transporters in Small Intestine (3)
Brush border
- SGLT1- Brings glucose and fructose into cell using potential energy of Na+ gradient so requires energy
- High affinity for glucose
- GLUT5- only works if sugars are moving down a conc gradient (so higher conc of sugars outside cell) so does not require energy
Basolateral membrane
- GLUT 2 -transports glucose out of cell and into portal circulation; also only works when glucose moves down a conc gradient so does not require energy
- Low affinity for glucose
Which tissues use insulin-dep glucose uptake?
fat cells, skeletal muscle, heart muscle
Which GLUT transporter is used in liver and why?
GLUT 2
- Because it has a low affinity for glucose, it is more contingent on the concentration of glucose; allows differences b/n fed and fasted states
Which GLUT transporter is used in brain and why?
GLUT 3 (neurons)
- HIGHEST affinity for glucose so highest rate of glucose transport - Ensures that brain gets glucose even in low-glucose state
Which GLUT transporter is used in muscle and why?
GLUT 4
- Insulin stimulates it to incorporate into membrane (insulin- dep because do not need glucose all the time)
Effects of hyperglycemia in diabetic patients
Chronic high blood glucose —> inc glucose uptake in cells that are insulin-independent (lens, retina, kidney and nerve cells) —> reacts w/ aldol reductase —> sorbitol
Sorbitol accumulation leads to tissue damage in these cells (blindness, cataracts, kidney problems and neuropathy)
Glycogen Structure
- Chains held together by alpha 1,4 glycosidic bonds then branches every 8-10 glucose molecules with alpha 1,6 glycosidic bonds
- Glycogenin protein core (autocatalytic)
Function of Glycogen in Muscle v Liver
Liver- maintain blood glucose levels (mobilize when blood glucose is low and store when blood glucose is high)
Muscle- for immediate energy needs during exercise (does not contribute to blood glucose in fasting state)
Glycogen Synthesis Reactions
Gluc —> glucose-6-P (+ glucose-1,6-bisphos intermediate) glucose-1-P —> UDP-glucose (“activated glucose”) —> added to glycogen
Glycogen Synthesis Enzymes
- Hexoinase (muscle) or glucokinase (liver)
- Phosphoglucomutase
- UGPase
- Glycogen Synthase (regulated enzyme/step)
Glycogen Synthesis Energetics
Step 1 requires 1 phosphate bond; step 2 is in equilibrium so no energy cost; step 3 requires -2 phosphate bonds and last step GAINS 1 phosphate bond
Net = -2
Synthesis of “Activated Glucose”
Synthesis: Glucose-1-P + UTP —> UDP-glucose + pyrophosphate
Pyrophosphate almost immediately turns into 2P so the above reaction occurs despite low deltaG b/c conc of pyrophosphate is so low )reacts immediately) that reaction is driven to the right
cAMP and Glycogen Synthesis v Mobilization
Synthesis: glucagon —> cAMP levels inc —> activate protein kinase A —> phosphorylates glycogen synthase which DEACTIVATES it (cAMP also inhibits protein phosphatase which would normally dephosphorylate glycogen synthase)
Mobilization: Glucagon/epinephrine —> inc cAMP — >act protein kinase A —> phosphorylates phosphorylase kinase A (active) —> phosphorylates glycogen phosphorylase
What happens to glycogen synthase after a high carb meal?
Inc insulin/glycogen ratio —> activates protein phosphatase 1 (PP1) —> dephos glycogen synthase (NOW ACTIVE) —> glycogen is formed
STORAGE
Glycogen Mobilization Enzymes
glycogen phosphorylase
Bifunctional Debranching Enzyme
Muscle Glycogen Phosphorylase v Liver Glycogen Phosphorylase
Muscle- responds to epinephrine; reg by energy state and cAMP and Ca++
Liver- responds to both epinephrine and glucagon; reg by glucose state of cell and cAMP; also inhibited by ATP though
Ca++ and Muscle Cells
Coordinates muscle contraction with glycogen mobilization b/c Ca++ contracts cell and activates phosphorylase kinase –> activates glycogen phosphorylase
Epinephrine alpha v beta receptors
Alpha- inc Ca++ (also inc IP3 in liver)
Beta- inc cAMP –> cascade
Von Gierke’s Disease
Deficiency in glucose-6-phosphatase …glucose cannot leave cell so hypoglycemia —> always hungry, fatigued, maybe stunted growth
McArdle’s Disease
Deficiency in muscle glycogen phosphorylase… muscle weakness, muscle cramps when exercising, excessive muscle glycogen stores
Treat by high protein diet and avoiding strenuous exercise
Glycogen Phosphorylase Deficiency in Liver v Muscle
- In liver glycogen phosphorylase …hypoglycemia, excessive liver glycogen stores so enlarged liver (Hers Disease)
- In muscle glycogen phosphorylase… muscle weakness, muscle cramps when exercising, excessive muscle glycogen stores (McArdle’s Disease)
Which tissues use insulin-indep glucose uptake?
All tissues except adipose and muscle
