2014/9/25

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

lactase

http://www.web-books.com/MoBio/Free/Ch4H1.htm

Lactose [galactosyl (14)-glucose] synthesis.

Protein B
only found in lactating mammary glands,
stimulated by prolactin.

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Galactose kinase
UDP-hexose

4-epimerase

GALT

Pathway for galactose metabolism

GALT = galactose 1-phosphate uridyltransferase

Remove fructose and

sucrose from the diet

Galactose converts to galactitol

Key concept map for metabolism of fructose and galactose

GALT = galactose 1-phosphate uridyltransferase

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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

(DHAP)

F 1-P

F 1,6-bisP

Phosphorylation products of fructose and their cleavage

Lippincotts Illustrated Reviews : Biochemistry, 2011

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Fructose metabolism as part of the essential

pathways of energy metabolism Lippincotts 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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Fructose and Health

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.
Bray GA et al., Am J Clin Nutr. 2004 Apr;79(4):537-43

Effect of fructose
on various organ systems

Johnson R J et al. Endocrine Reviews 2009;30:96-116

Euglycemic
hyperinsulinemic clamp
is a technique to assess
insulin resistance in
human and experimental
animals

Basciano A et al. Nutr Metab 2:5-18, 2005

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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 (ethanolinduced oxidative stress)

ethanol

acetaldehyde

Acetic acid

AceCS
ATP + acetate + CoA <> AMP + PPi + acetyl-CoA

ADH Alcohol dehydrogenase (cytosolic)

ALDH Aldehyde dehydrogenase (mainly mitochondrial)
AceCS Acetyl-CoA synthase (cytosolic & mitochondrial)

Cederbaum AI. Clin Liver Dis 16:667-685, 2012

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*inducible and applicable in chronic consumption

Elamin EE et al. Nutrition Reviews 71:483-499, 2013

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 -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?

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