Glucose

AcetylCoA

Pyruvate

NADH/FADH2

Citric AcidCycle

C6

C4

C5

C4

ATP

Glycolysis

Bridging Rx.

OP

ADP O2

Metabolic Mainstreet

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

Glycolysis

Bridging Rx.

OP

ADP O2

Metabolic Mainstreet

NAD+

NADH Aerobic~ 36 ATP

Glycerol phosphate shuttle

Lactate

Anaerobic 2 ATPLDH

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

Glycolysis

Bridging Rx.

OP

ADP O2

Glycogen Metabolism liver & muscle

Glycogen¬ Glycogenolysis fasting state – glucagon muscle - epinephrine

Fed state - insulinGlycogenesis →

Glucose-6-P

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

ADP O2

NAD+/FAD

oxaloacetate

Gluconeogenesis (liver) Protein

Ubiquitin /Proteosome

Amino Acids

TransaminationOxidative deamination

glucogenic

glucogenic

ketogenic

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

OP

ADP O2

Lipase (fasting)

Fat (triglycerides) (adipose)

fed

b-oxidation

Fatty acidsFatty acid synthesis

NADPHCO2

Ribose-5-P

PPPTK/TA

acetoacetylCoAketone bodies (liver)

Citric AcidCycle

Metabolism & Cell Type

• Brain: Glucose only (normal)

adapts to 75% KB utilization (long term fast)

• Liver: Exports Glucose via glycogenolysis and gluconeogenesis

makes Fatty acids/cholesterol (fed) – ketone bodies (fast)

• Muscle: Maintains glycogen to allow anaerobic metabolism • Adipose: Fat storage – Lipase (glucagon) - leptin secretion

• Heart Muscle: KB’s as fuel – avoid anaerobic activity

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

Glycolysis

Bridging Rx.

OP

ADP O2

Metabolic Mainstreet

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

Glycolysis

Bridging Rx.

OP

ADP O2

Brain Cells fed + early/late fast

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

25% from LiverGluconeogenesis

OP

ADP O2

Brain Cells Long term fast

acetoacetylCoAketone bodies (from liver)

75%

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

OP

ADP O2

Fatty acids

Fat (triglycerides)

Fatty acid synthesis

NADPHCO2

Ribose-5-P

PPPTK/TA

Adipose: Fed state

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

OP

ADP O2

Fatty acids

Fat (triglycerides)

Lipase (fasting)

b-oxidation

Adipose: fasting state

to blood

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

Glycolysis

Bridging Rx.

OP

ADP O2

Musclefed state at rest

GlycogenGlycogenesis

Glucose-6-P

Fatty acids

b-oxidation

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

Glycolysis

Bridging Rx.

OP

ADP O2

Muscle Anaerobic exercise

GlycogenGlycogenolysis

Glucose-6-P

Fatty acids

b-oxidation

LactateLDH

Muscle McArdle’s Disease

X

X

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

OP

ADP O2

Fatty acidsFatty acid synthesis

NADPHCO2

Ribose-5-P

PPPTK/TA

Liver: Fed state

to bloodGlycogen

GlycogenesisGlucose-6-P

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

Glycolysis

Bridging Rx.

OP

ADP O2

Liverearly fast Glycogen

GlycogenolysisGlucose-6-P

Fatty acids

b-oxidation

to blood

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

ADP O2

NAD+/FAD

oxaloacetate

Gluconeogenesis Protein

Amino AcidsFatty acids

ketone bodiesacetoacetylCoA

blood

Liver late fast

also indiabetesfed state

Citric AcidCycle

Glucose

AcetylCoA

Pyruvate

NADH/FADH2C6

C4

C5

C4

ATP

ADP O2

NAD+/FAD

oxaloacetate

Gluconeogenesis Protein

Amino Acids

Fatty acidsacetoacetylCoA

ketone bodies

blood

Liver long term fast

Citric AcidCycle

Fedstate

[Glu]blood

Meal~12 hrs

~2 hrs

Glycogen broken down to provide glucose

Insulin release

Glucagon release

Blood Glucose concentrations normal fasting levels = 60 – 100 mg/dL

[Glu]blood

Meal

Insulin

Glucagon

Fed

Fast

early

late fast

Glycogen gone

6-12 hrs1-2 hrs

~ 3 days

Fasting State

early

late

long term

LipolysisBrain usesKetone bodiesProtein conserved

Protein broken down to make glucoseFatty acids from adipose

Glycogen broken down to provide glucoseFatty acids from adipose

Absent with Atkins Meal – lipolysis continues

Fed[Glu]blood

Meal~12 hrs~2 hrs

high glycemic index – low fat dietdiabetic

Atkins

insulin resistance (metabolic syndrome)

60 – 100 mg/dL

1992 USDA Food Pyramid - Low fat diet fads

Bread, cereal, rice, pasta 6-11

Vegetables 3-5 Fruits 2-4

Dairy Meat, Fish 2-3 Eggs, Beans 2-3

Fats use sparingly

What constitutes low fat? < 30% of calories from fat extreme diet < 10%

Healthy Eating Pyramid

Exercise & weight control

Vegetables (lots) Fruits 2-3

Fish, poultry, eggs 0-2

use sparingly

Whole grain Plant oils

Nuts & legumes 1-3

Dairy/Ca supp 1-2Multiple vitamin

Red meat, butter, white rice, bread, potatoes, pasta, sweets

Willett, Walter (2005). Eat, Drink, and Be Healthy: The Harvard Medical School Guide to Healthy Eating. Free Press. ISBN 0-7432-6642-0

2001 USDA Food Pyramid (www.MyPyramid.gov)

Grains 8 oz. 4 oz. whole grain

Vegetables 3 cups weekly

Fats sugars Na use sparingly

Meat & beans: lean meats more fish, beans, nuts, peas, seeds

Fruits 2 cups weekly

Milk 3 cups (Ca rich foods – low fat)

7 teaspoon = daily limit on oils

‘FAD’ Diets

Atkins Diet ― very low carbohydrate (no portion limits)

South Beach Diet ― milder form of Atkins

Zone Diet ― 40:30:30 (% of calories from carbohydrate – protein – fat)

Mediterranean Diet ― 40% calories from fat but monounsaturated

‘Eating Plans’

Willet – Healthy eating Pyramid

USDA – 1992 Food Pyramid 2001 Food Pyramid

Common Features: 1) exercise 2) Eat your Veggies

Majority Features: 1) minimize saturated fats 2) minimize high Glycemic index Carbs 3) replace 1-2 with whole grains/fruits/unsaturated fats 4) portion control

Low Fat Diet ― < 10% calories from fat

Our hunter-gatherer ancestors relied on a wide variety of fruits and vegetables, scrabbling to pick and eat whatever they could find that was tasty. Desire for carbohydrates (sweetness) was balanced by its scarcity, and existed only in forms that included high fiber.

Random dietary advice …..Hydration – page 129 – tap water (over-hyped water in food counts)Diet drinks – page 130 (safe - better than sugar drinks – water is best)Coffee – 132-133 (safe in moderation, beware caffeine)tea – 134 (less caffeine than coffee, more antioxidants )alcohol – 135-137 (moderation! – 1-2 drinks ok for men –breast cancer correlation in women)

Ca – 151 (over-hyped – 500-1000 mg supplements (> dairy) for post-menopausal women)

Antioxidants – 154 – 157 (over-hyped – drink tea, eat fruits/veggies)

Vitamin C – 161 (over-hyped – RDI = 75 mg/day; 200-300 probably good)

Fe – 169-170 (not a major problem in US)

Na - 173-174 (minority predisposed to hbp - we get too much in diet - ↓processed foods)

fiber – 97 – 98 (cancer benefit probably false but - ↓cholesterol and ↓Glycemic index)

Protein – 0.4g • body weight (in lbs) – 104 (nuts/veggie sources > lean meats > red meat)