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Metabolism of common dietary saccharides and alcohol
Lactose
milk sugar, a disaccharide consisting of glucose & galactose
lactase deficiency
Fructose
a common food ingredient and implicated in the
development of certain chronic diseases
Ethanol
social drinking
chronic alcoholics
impact on people with compromised hepatic function
http://www.web-books.com/MoBio/Free/Ch4H1.htm
Lactose [galactosyl β (14)-glucose] synthesis.
Protein B only found in lactating mammary glands,
stimulated by prolactin.
lactase
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Pathway for galactose metabolism
GALT
Galactose kinase
GALT = galactose 1-phosphate uridyltransferase
UDP-hexose
4-epimerase
Key concept map for metabolism of fructose and galactose
GALT = galactose 1-phosphate uridyltransferase
Galactose converts to galactitol
Remove fructose and
sucrose from the diet
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Fructose
Dietary sources: as fructose (fruit sugar, honey) or high fructose corn
syrup (in soft drink)
• GLUT 5 transcription increases with increase fructose availability
•Entry into cells is NOT insulin-dependent
•Does not promote insulin secretion
http://en.wikipedia.org/wiki/Fructose
Phosphorylation products of fructose and their cleavage
(DHAP)
Lippincott’s Illustrated Reviews : Biochemistry, 2011
F 1-P F 1,6-bisP
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Fructose metabolism as part of the essential
pathways of energy metabolism Lippincott’s Illustrated Reviews : Biochemistry, 2011
• Hexokinase has low affinity for fructose
with the presence of glucose to saturate hexokinase,
little fructose is phosphorylated by hexokinase (to
form F 6-P).
• Fructokinase (found in liver and intestine) converts F to F 1-P
• F 1-P is then cleaved by Aldolase B
• Rate of F metabolism is more rapid than G
trioses formed from F 1-P bypass PFK-1 regulation, the
rate limiting step in glycolysis
What are the metabolic consequences of chronic high
fructose intake?
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Johnson R J et al. Endocrine Reviews 2009;30:96-116
Bray GA et al., Am J Clin Nutr. 2004 Apr;79(4):537-43
Total fructose : the sum of free fructose and fructose that is part of the disaccharide sucrose. Free fructose: the monosaccharide in HFCS and is also obtained in small amounts from other sources.
Fructose and Health
Effect of fructose on various organ systems
Basciano A et al. Nutr Metab 2:5-18, 2005
Euglycemic
hyperinsulinemic clamp
is a technique to assess
insulin resistance in
human and experimental
animals
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Nutrition Reviews 63:133-157, 2005
?
Basciano A et al. Nutr Metab 2:5-18, 2005
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Impacts of alcohol consumption on intermediary metabolism
~ 80% absorbed in duodenum and 20% in the stomach 7 kcal per gram of ethanol Main site of metabolism is the liver, but metabolites could also affects organs such as the CNS (ethanol-induced oxidative stress)
Cederbaum AI. Clin Liver Dis 16:667-685, 2012
ADH – Alcohol dehydrogenase (cytosolic)
ALDH – Aldehyde dehydrogenase (mainly mitochondrial)
AceCS – Acetyl-CoA synthase (cytosolic & mitochondrial)
AceCS
acetaldehyde
Acetic acid
ethanol
ATP + acetate + CoA <——> AMP + PPi + acetyl-CoA
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Elamin EE et al. Nutrition Reviews 71:483-499, 2013
*inducible and applicable in chronic consumption
Elamin EE et al. Nutrition Reviews 71:483-499, 2013
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Major metabolic consequences of
heavy / chronic drinking
Ethanol metabolism leads to
1. Depletes NAD+, excess NADH
What would happen to glycolysis?
What would happen to gluconeogenesis?
What would happen to β-oxidation?
What would happen to TCA cycle?
What is the overall consequence?
2. Alcoholics have acidosis, why?
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Metabolic disruptions in liver due to alcohol metabolism: Hepatic metabolism
of ethanol (alcohol) results in the generation of large quantities of cytosolic and
mitochondrial NADH leading to disruptions in the normal metabolic processes in
the liver. Acute and chronic ethanol metabolism results in impaired
gluconeogenesis leading to potentially severe hypoglycemia. The elevated
cytosolic NADH levels lead to diversion of pyruvate into lactate, as well as an
inability to convert lactate to pyruvate which represents the major disruption in
normal hepatic gluconeogenesis. The increased lactate production in turn results
in excessive lactate delivery to the blood and a consequent lactic acidemia. In
addition, chronic ethanol metabolism leads to impaired fatty acid oxidation and a
diversion of carbons into fats which results in increased triglyceride and VLDL
production causing fatty infiltration and ultimately liver damage and failure.
Contributing to the progression to liver damage and failure is the increased
production of reactive oxygen species (ROS) within the mitochondria as a
consequence of the increased levels of mitochondrial NADH. The ROS cause
mitochondrial stress leading to the triggering of the mitochondrial apoptosis
pathway and hepatocyte death.
http://themedicalbiochemistrypage.org/ethanol-metabolism.php#metabolism
Blood glucose concentrations
following ingestion of food with
low or high glycemic index.
How would a low GI food affect
intermediary metabolism?