Carbohydrate Metabolism I

amylose vs amylopectin

- amylose- linear, α 1-4, 15-20%

- amylopectin- branched, α 1-4 and 1-6, 80-85%

cellulose

- major component of cell walls

- rely on gut bacteria to ferment it into SCFA (~2kcal/g)

CHO recommendations

- 45-65%

- 130g/d (for brain)

- 1/2 from whole grain (rest is fortified)

CHO intake

- currently around 45-50%

- sources: cereals, sugar, roots, pulses, F/V, milk

sugar recommendations

- Institute of Medicine (DRI): ≤ 25% of total energy intake as added sugar

- WHO: ≤ 10% of calories from free sugars (12tsp, 50g)

free sugars

mono and disaccharides, anything that's added to a food/drink by consumer/manufacturer, or found naturally occurring in foods (doesn't include sugars from milk or fruit)

sugar intake

- 9%

- SSB has decreased

role of sugar in nutrition

Adults with moderate sugar intakes had higher consumption of dietary fiber, calcium, vitamin D, potassium -> greater intakes of fruit and dairy

Salivary α-amylase

- Only hydrolyzes α 1-4 bonds

- Becomes inactivated in the stomach (works best in neutral environment)

- Products: dextrins (short-chain polysaccharides, few maltose, few monosaccharides)

Pancreatic α-amylase

- Hydrolyzes α 1-4 bonds

- Products: oligosaccharides (dextrins), maltose and maltotriose

what is amylose broken down into?

glucose, maltose and maltotriose, then specific glycosidases

what is amylopectin broken down into?

glucose, maltose and isomaltose; α 1-6 is hydrolyzed by isomaltase

brush border enzymes

brush border of the upper small intestine

- Lactase: Lactose (β 1-4) → glucose, galactose

- Sucrase: Sucrose → glucose, fructose

- Maltase: Maltose → 2 glucose

- Isomaltase: Isomaltose (α 1-6) → 2 glucose

absorptive capacity of glucose and fructose

5400 g/d glucose, 4800 g/d fructose

SGLT1

- brings in 1 glucose/galactose for every 2 Na+ into intestinal cell

- secondary active transport

- in Jejunum > duodenum > ileum

- target for metformin

how do glucose and galactose leave mucosal cell?

- 15% leaks back into lumen

- 25% diffuses through basolateral membrane

- 60% by GLUT 2 (facilitative)

GLUT2

- absorbs glucose, galactose and fructose

- high concentrations in lumen increases GLUT2 in apical membrane

fructose absorption

- GLUT 5 and then GLUT 2 (both facilitative)

- ↑ GLUT2 on apical membrane = ↑ fructose absorption

- Rate of transport is slower than glucose, galactose

how does insulin regulate glucose absorption?

↑ Insulin (↑ glucose) = ↓ GLUT2 on apical membrane (negative feedback loop, slows absorption)

*insulin signals that sugar is being taken into cell, slows rate of absorption

feed-forward mechanisms in glucose sensing and signalling

- glucose sensing cells in the gut, can secrete things into the body to alert arrival of glucose

- incretins: gut-derived hormones, released in response to nutrient ingestion

- slows gut motility, gastric emptying (appetite effects)

- e.g. GIP, GLP1, GLP2

where is glucose distributed?

- liver is priority (galactose and fructose converted to glucose)

- when you have low levels of muscle glycogen, prioritizes muscles over liver

Fate of glucose once in the liver

- Bloodstream

- Oxidation

- Storage

insulin-dependent vs insulin independent glucose uptake

dependent- muscles

independent- kidney, liver, brain

GLUT1

always on membrane of muscles

nutrients that act as insulin secretagogues

- Glucose**

- Amino acids (e.g., leucine)

- NEFA (non-esterified fatty acids ie. FFA)

phases of insulin secretion

1. begins within a few minutes of stimulation (from storage vesicles of insulin, triggered by incretins)

2. begins a few minutes after first phase and peaks at 30-40 min (production of insulin)

how does glucose allow insulin to be released from beta cells?

1. glucose binds to receptor (ie. GLUT2), burned to ATP

2. elevation of ATP causes flux of K+ out of cell → depolarization

3. Ca2+ comes in and triggers release of insulin from secretory vesicles

*in alpha cells, K+ and Ca2+ channels are shut down to prevent glucagon secretion

insulin signaling steps

1. insulin binds to receptor, causes autophosphorylation of beta subunit

2. activated tyrosine kinase of the insulin receptor P IRS-1.

3. cascade

4. leads to the trafficking of GLUT4 vesicles from storage in the cell to the plasma membrane.

5. GLUT4 transports in glucose

normal blood glucose levels

Fasting: <6.1 mM (3.3 to 5.6 mM)

Post-prandial (2 hr): <7.0 mM

hormone levels with increased blood glucose

↑ insulin, ↓ glucagon

↑ glucose uptake → ↑ storage, ↑ oxidation

hormone levels with decreased blood glucose

↓ insulin, ↑ glucagon

↑ breakdown, ↑ production (liver only; ↑ cortisol)

glycogen storage

- stored in granules

- liver has greater capacity to store glycogen per cell, but muscle stores more glycogen overall

liver and glycogen

- Major site of glycogen synthesis and storage

- Accounts for 7% of the wet weight of the liver

- Glycogen → Glucose*

- used to keep blood sugar stable

- lots of hormonal control (e.g. glucagon, cortisol)

muscle and glycogen

- 75% of body's glycogen is stored here

- Accounts for <1% of the wet weight of muscle

- Used as an energy source → ATP

- does not have glucose-6-phosphatase

glycogenesis steps

1. Glucose enters the cell

2. Glucose phosphorylated → G-6-P (glucokinase, hexokinase)

3. G-6-P → G-1-P (phosphoglucomutase)

4. G-1-P → UDP-glucose

5. Glycogen synthase adds UDP-glucose to an existing glycogen chain

6. Branching enzyme (α 1-6 bonds) also needed

hexokinase

- phosphorylates glucose in muscle

- uses ATP

- modulated by G-6-P

- cannot be reversed in muscle

- Lower Km- doesn't need a lot of glucose to work

glucokinase

- uses ATP

- no affect by G-6-P (allows rapid entry)

- Higher Km (high velocity, lower affinity)- needs a lot of glucose to work

what is the rate limiting enzyme of glycogenesis?

Glycogen synthase

glycogenolysis steps

1. Cleavage of 1 unit at a time (G-1-P) from non-reducing ends (by glycogen phosphorylase, needs debranching enzyme for α 1-6 bonds)

2. G-1-P to G-6-P (glucose P isomerase)

3. G-6-P to free glucose (glucose-6-phosphatase)

glycogen phosphorylase in liver

- Glycogen is needed to provide free glucose

- Regulated by hormones moreso (e.g. glucagon)

glycogen phosphorylase in muscle

- Glycogen is needed for energy

- Insensitive to glucagon

- Allosteric inhibitors: ATP, G-6-P, free glucose

- Allosteric activators: 5'AMP (energy sensor, product of 2 ADP broken down)

- Also stimulated by Ca2+, nervous system, epi, norepi

products of glycolysis

net: 2 pyruvate, 2-3 ATP, 2 NADH

(produces 4 ATP, but 2 are used)

anaerobic fate of pyruvate

- converted to lactate (strenuous exercise)

- Lactate to liver (substrate for gluconeogenesis)

- Small amount of energy provided (+2 or 3 ATP)

- RBCs, brain, GI tract

aerobic fate of pyruvate

- TCA (mitochondria) - Large amounts of energy (+38 ATP)

- Production of some lactate occurs

other fates of pyruvate

- transaminated to Alanine

- amino group is used from glutamate)

important steps of glycolysis

- Hexokinase/glucokinase phosphorylates glucose to G-6-P (uses 1 ATP)

- 1 hexose → 2 trioses G3P, DHAP (G3P is favored and uses 1 ATP)

- 2 ATP formed at phosphoglycerate kinase step

- 2 ATP formed at PEP step and 2 pyruvate

PFK

- major rate limiting enzyme of glycolysis

- Consumes 1 ATP

- activated by F6P, AMP, ADP, F-2,6-biP

- inhibited by ATP, citrate

- Induced by glucagon