7_galactose fructose alcohol (m2014)

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2014/9/25 1 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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Page 1: 7_Galactose Fructose Alcohol (m2014)

2014/9/25

1

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

Page 2: 7_Galactose Fructose Alcohol (m2014)

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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

Page 3: 7_Galactose Fructose Alcohol (m2014)

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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?

Page 10: 7_Galactose Fructose Alcohol (m2014)

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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?