Fructose and galactose metabolism, Metabolism Midterm

Dr. Jones LLU

Fructose is a _____ monosaccharide

ketonic

Fructose is the ___ of all natural carbs

sweetest

Sources of fructose

• sucrose- disaccharide (glucose + fructose with a(1-2) bond), esp in sugar cane and beets

• free fructose - honey and fruit

• high-fructose corn syrup (HFCS)- mixture of monosaccharides- 55% fructose, 45% glucose

Sucrose is not a ____- no open ring with aldehyde

reducing sugar

In open chain form, carbonyl carbon is ___ on D-fructose

carbon 2

OH that forms below plane is ___, above is ___

alpha, beta

Galactose: ___ epimer of glucose, ___ sweetness of sucrose

C4, 1/3

Sources of galactose:

• lactose- disaccharide

  • galactosyl B(1,4)-glucose

  • found in dairy products

• glycosylated proteins

Epimer: a type of isomer in which ____ of the asymmetric carbons is different

only one

Galactose is a____ sugar, glucose ring can still open

reducing

Lactose is only found in…

milk and milk products

Glycosylated means a __has been added

sugar atom

Invert sugar: mixture of ___and ___, made by hydrolysis of ___, resultant monosaccharides have the ___ optical rotation of the original molecules, often used in baking

sucrose and fructose, sucrose, opposite

Maltose: a disaccharide composed of two…

glucose molecules

Fructose and galactose digestion: ___ enzymes: ___ hydrolyzes sucrose into ___ +____, lactase hydrolyzes lactose into ___and ___

brush border, sucrase, glucose+fructose, glucose and galactose

Amylase ___ break down a disaccharide

cannot

We only absorb ___ into the epithelial cells

monosaccharides

Sugars are highly ___, require ____: SGL-1

polar, transporters

SGL-1 is in the…

kidney

Fructose enters the enterocyte by ____ on the ___ membrane (___ affinity for fructose)

GLUT5, apical, high

Fructose leaves the enterocyte by ____ on the ____ membrane → ___

GLUT2, basolateral, portal vein

After a high-carb meal, GLUT2 on the apical membrane ___ fructose absorption

increases

Galactose: enters the enterocyte by ___ on the ___ membrane- ___ active transport

SGLT1, apical, secondary

Galactose leaves the enterocyte by ___ on the ___ membrane → ___

GLUT2, basolateral, portal vein

Fructose transporter:

GLUT5

SGLT1 requires ___ to work

ATP

GLUT5 is a facilitated transporter specific for ___, predominantly on apical membrane of the small intestine

fructose

GLUT2: low ____, high-capacity facilitated transporter for…

affinity, glucose, galactose, fructose, mannose, glucosamine

GLUT2 is found in the…

small intestine, liver, pancreatic B-cells, kidney

When large amounts of glucose enter the enterocyte, ___ is moved form vesicle storage sites to the ___ membrane

GLUT2, apical

After a high-carb meal, more glucose enters the cell by ___ than by ___

GLUT2, SGLT1

Insulin triggers ____ to move back to vesicle storage, insulin resistance → ___

GLUT2, higher absorption rate

SGLT-1: secondary active transporter for ___ and ___, driven by symport of Na+ ions

glucose, galactose

In the liver, all ___ monosaccharides absorbed by ____

3, GLUT2

Hepatic GLUT2 is bidirectional, not ____: works in ___and ___ state

insulin sensitive, fed and fasting

essentially all galactose and fructose is taken up by the…

liver

Upon cell entry, fructose must be ____ to keep it in the cell

phosphorylated

fructose phosphorylation equation

Fructose + ATP → fructose 1-phosphate + ADP

Enzymes for fructose metabolism:

• ____, present in non-hepatic tissues- not ____, as most fructose is removed from circulation by liver

• ____, (main) present in hepatocytes, kidney, small bowel- low Km for fructose

• hexokinase, significant, fructokinase

Fructose 1-P is cleaved into trioses: _____, by…

frucose 1-phosphate → DHAP + glyceraldehyde; aldolase B (laso fructose 1-P aldolase)

Fructose metabolism is more ___than glucose metabolism because triose production bypasses ____(major rate-limiting step of glycolysis)

rapid, PFK-1

Glyceraldehyde can be phosphorylated by triose kinase into…

glyceraldehyde-3-phosphate

Acetyl-CoA is the precursor to make…

fatty acid

No pathway in the fed state for fructose to end up as…

glycogen

What is the fate of DHAP? may be converted to ___ by ____ to enter glycolysis or gluconeogensis, may be converted to ___ by ____ for use in TAG synthesis

G3P, triose phosphate isomerase, glycerol 3-P, glycerol 3-P dehydrogenase

What is the fate of glyceraldehyde? may be converted to ___ by ___- G3P may enter ___(in fed state) or ____(in fasting state) or G3P→ DHAP → glycerol 3-P

G3P, triose kinase, glycolysis, gluconeogensis

Hereditary fructose intolerance:

• autosomal ___deficiency of ___ leads to intracellular ___ of fructose 1-P

• causes severe hypoglycemia, ___, ___, hemorrhage, hepatomegaly, renal dysfunction, hyperuricemia, and lactic acidemia

• ___,___ and ___ can cause ____ failure and death

• treatment is removal of ___ and ___ from diet

• recessive, aldolase B, trapping

• vomiting, jaundice

• fructose, sucrose, and sorbitol

• fructose and sucrose

Sucrose is split to ___ and ___, glucose made to ___

glucose and fructose, glycogen

Galactose metabolism: transport into cells by ___, not ___ dependent

GLUT2, insulin

Upon cell entry, galactose must be _____ for further metabolism

phosphorylated

Galactokinase phosphorylates with ____ as P donor to form _____

ATP, galactose 1-P

Galactose 1-P uridylyltransferse (GALT) activates _____- galactose in exchange reaction

galactose 1-P to UDP

UDP-hexose 4-epimerase isomerizes UDP-galactose to its C4 epimer UDP-

glucose

UDP-glucose can then enter ____ or activate more galactose 1-P. UDP-galactose may also be used in synthetic reactions

glycogenesis

•Phosphorylates galactose to galactose-1-P

Galactokinase

•Transfers a UMP group from UDP-glucose to Gal-1-P to form UDP-galactose

Galactokinase-1-P uridyltransferase

•Interconverts UDP-galactose and UDP- glucose

•UDP-glucose is may be added to glycogen

•UDP-galactose-4’-epimerase

UDP-glucose pyrophosphorylase:

•Converts glucose-1-P to UDP-glucose

In a fed state, most galactose is funneled into ___

glycogen synthesis

Classic galactosemia: ____ deficiency

• autosomal ___ disorder

• causes galactosemia, galactosuria, ___, diarrhea, and jaundice

• accumulation of ___ and ___ in nerves, lens, liver, and kidney tissue causes ___, severe mental retardation, and cataracts

• prenatal diagnosis is possible by chorionic ___ sampling, newborn screening available

• therapy: rapid ___ and ___ of ____(and therefore lactose) from diet

• despite adequate treatment, at risk for ___, and in females, premature ___ failure

GALT

• recessive

• vomiting

• galactose 1-phosphate, galactitol, liver damage

• villus

• diagnosis, removal, galactose

• developmental delays, ovarian

_____ in the small intestine breaks down lactose into glucose and galactose

Lactase

In many people, lactase activity ____ dramatically in childhood & adolescence to 5-10% of activity at birth

declines

when inadequate lactase is to present to handle a load of ingested lactose, ____occurs

lactose intolerance

lactose intolerance pathophysiology: undigested molecules attract water, causing…

bloating, abdominal discomfort, diarrhea