Download Baumgard Post absorptive CHO metabolism

AnSci 519
Post-Absorptive CHO Metabolism
Lance Baumgard
CHO digestion and absorption:
monogastric vs ruminants
Digestive feature
Ruminants
Monogastric
Salivary amylase
Zero
Varies with species, High in
primates, moderate in pigs
and low in strict carnivores
Pregastric fermentation
Extensive
Zero
Gastric digestion
V. Low
V. Low
Pancreatic amylase
Lowmoderate
V. High
Intestinal glucose
absorption
High
Zero/low
Post-Absorptive Terminology
• Catabolism
– Breaking down of a nutrient or tissue
• Anabolic
– Creating/synthesizing a tissue
• Oxidation
– Utilizing a nutrient to generate ATP, CO2 and H20
• Glycolysis
– Breaking down of glucose…into pyruvate
• Gluconeogenesis
– Making of glucose…from non carbohydrate precursors
• Glycogen
– Storage form of glucose (Liver and muscle)
• Glycogen synthesis (glycogenesis)
• Glycogenolysis
• TCA Cycle
– Products of glycolysis enter TCA cycle and generate ATP
Primary Potential Fuel Sources
• Volatile Fatty Acids (VFA)
– Primarily in ruminants
– Controversy on how much large intestine VFA in
monogastrics contribute to energy
• Non-Esterified Fatty Acids (NEFA): a.k.a Free Fatty acids
– From adipose tissue break down
• Amino Acids
– Efficiency of capturing ATP from AA oxidation is very
poor……large amount of heat released
• Glucose
– Absorbed from GIT
– Released from liver (and kidney during starvation)
• Gluconeogenesis and glycogen breakdown
– Stored in muscle
Sources of blood glucose
Source
CHO digestion
Tissue site
Sm. Int (m. gastric)
Propionate (rum.)
Glycogen breakdown
Liver
Gluconeogenesis
Liver, kidney
Post-absorptive glucose metabolism
• Options for absorbed glucose
Catabolic
– 1) Oxidation: produces CO2 and H20
– 2) Glycolysis:
• Production of pyruvate
– TCA cycle (with O2)
– Lactate (with no O2)
Anabolic
– 3) Stored as glycogen
– 4) Stored as fat
– 5) Carbons utilized for amino acid synthesis
Types of Metabolic Pathways
Catabolic Pathways: produce free energy compounds
Anabolic Pathways: utilize these compounds
Overview
of Dietary
Catabolism
Glucose
•
The most important metabolic fuel in monogastrics are glucose and fatty
acids.
•
The most important metabolic fuel in ruminants is acetate
•
In normal circumstances, glucose is the only fuel the brain uses
– Can use ketones during starvation
•
Adult human brain requires ~120 g glucose/day
–
–
–
–
Whole body only requires ~160 g/glucose/day
~20 g of glucose in circulation
Liver glycogen stores about ~150-180 g of glucose
Muscle glycogen stores about ~300-350 g of glucose
• Only the liver can secrete/release glucose
• Muscle can not
Glucose
• To ensure the continuous provision of glucose to
the brain and other tissues, metabolic fuels are
stored when food is plenty
• To provide glucose over longer periods, the body
transforms non-carbohydrate compounds into
glucose through gluconeogenesis.
– Amino acids, lactate and glycerol
Glucose
Oxidation
Glycolysis (10 successive reactions)
2 Pyruvate
Cytosol
Mitochondria
2 Acetyl CoA
O2
TCA
Cycle
NADH
Electron Transport Chain
CO2
ATP
Glycogen
• Glycogen synthesis
– Occurs in the liver and muscle
– The synthesis of a branched polysaccharide form
glucose….resembles amylopectin
– Liver stores are especially important as an
emergency source of blood glucose
• Glycogenolysis
– Breakdown of glycogen into glucose
– Liver secretes the glucose, muscle only oxidizes
glycogen released glucose
Gluconeogenesis
Propionate
(gut)
Amino Acids
Glycerol
(fat mobilization)
Glucose
Lactic Acid
(Gut & Cori Cycle)
(gut, muscle)
– Gluconeogenesis
• Glucose requirements
– Central nervous system
» 15 – 20% of glucose utilization
– Pregnancy
» For fetus
– Lactation
» Lactose synthesis
– Lipid synthesis
» NADPH for fatty acid synthesis
» Glycerol
– Precursors for gluconeogenesis
Precursor
Propionate
Amino acids
(Primarily Alanine,
Glutamine, Glutamate)
Lactate
Glycerol
% of Glucose from:
Fed
Fasted
40 – 60
0
15 – 30
35
15
5
40
25
Gluconeogenesis
Glucose
Pyruvate
Lactate and Amino acids
Acetyl CoA
OAA
TCA
Cycle
Amino Acids
Propionate
(from rumen fermentation)
– Mechanism of gluconeogenesis
– Controlling enzymes
• Pyruvate carboxylase
(Pyr > OAA)
• NAD-malate
dehydrogenase
(Mal > OAA)
• PEP carboxykinase
(OAA > PEP)
• Fructose-1,6diphosphatase
(Fru-1,6-P > Fru-6-P)
• Glucose-6-phosphatase
(Glu-6-P > Glu)
– Hormones
• Glucagon and
Glucorticoids
• Insulin
From Van Soest, 1994
Hormonal Control of Glucose Homeostasis
• Insulin
–
–
–
–
–
Synthesized by the pancreas
Stimulated by increased glucose concentrations
Causes glucose storage (glycogen and fat)
Shuts down gluconeogenesis
Shuts down glycogenolysis
• Glucagon
– Synthesized by the pancreas
– Stimulated by a reduction in glucose
concentrations
– Stimulates glycogenolysis AND gluconeogenesis
• Epinephrine
– Synthesized by the adrenal gland
– Causes immediate glycogenolysis
– Increase glucose during “flight or fight”
Glucose Coordinators
Insulin
Anabolic
Glucagon
Epinephrine
Cortisol
Lipogenesis/Lipolysis
Gluconeogenesis/Glycolysis
Glycogenolysis/Glycogen Synthesis
Catabolic
Insulin Release
Insulin secretion in beta cells is triggered by rising blood glucose levels. Starting
with the uptake of glucose by the GLUT2 transporter, the glycolytic phosphorylation
of glucose causes a rise in the ATP:ADP ratio. This rise inactivates the potassium
channel that depolarizes the membrane, causing the calcium channel to open up
allowing calcium ions to flow inward. The ensuing rise in levels of calcium leads to
the exocytotic release of insulin from their storage granule.
Insulin Action
Insulin binding to the insulin receptor induces a signal transduction cascade which
allows the glucose transporter (GLUT4) to transport glucose into the cell.
Insulin vs. Glucagon
pancreatic islet
b cells
glucose
insulin
glucose
glucose
glucose
GI tract
fat cells
muscle
pancreas
Amino acids
liver
Insulin
Glucagon
Nutrient Director
Glucose
Circulating Nutrients
fat
Fatty acids
Amino acids
Glucose
Fatty acids
GIT
WELL FED ANIMAL
High insulin levels
Low glucagon and epinephrine
muscle
pancreas
Amino acids
liver
Insulin
Glucagon
Nutrient Director
Glucose
gluconeogenesis & glycogenolysis
Circulating Nutrients
fat
Fatty acids
Amino acids
Glucose
Fatty acids
GIT
HUNGRY ANIMAL
Low insulin levels
High glucagon and epinephrine
History of Insulin
• 1869 Paul Langerhans (German) was studying the
structure of the pancreas when he noticed exocrine tissue.
The function of the "little heaps of cells", later known as
the Islets of Langerhans
• 1889 German physician Oscar Minkowski removed the
pancreas from a healthy dog to demonstrate the
pancreas’s assumed role in digestion.
– Several days after the dog's pancreas was removed, he
noticed a swarm of flies feeding on the dog's urine
• 1921: first patient injected with canine insulin
• 1922: Eli Lilly purchases the patent for making insulin from
the University of Toronto for $1
• 1980: Eli Lilly marketed the first synthetic insulin, Humulin
(genetic engineered)
Type I Diabetic Female
Pre and Post insulin treatment
Epinephrine produced by adrenal glands
meal
100
90
80
absorption
gluconeogenesis
Reciprocity in patterns
glycogenolysis
Time after feeding (h)…
temporal pattern relative to CHO meal
Glucagon
Glucose
Insulin
Meal
Boo!
Glucose
Epinephrine
Post absorptive CHO metabolism:
ruminants vs. monogastrics
• Monogastrics:
–
–
–
–
Oxidize glucose for energy and energy storage
Blood glucose averages 80-100 mg/dl
Gluconeogenesis occurs many hours after a meal
Much of circulating glucose is diet derived
• Ruminants:
– Oxidizes acetate for energy and energy storage
– Gluconeogenesis immediately after meal
• ~100% of circulating glucose is derived from
gluconeogenesis
– Blood glucose averages 40-60 mg/dl
– Circulating glucose is NOT derived from diet