CFB 10 - Biochemistry: Other Sugars & Alcohol Metabolism

A complete set of vocabulary flashcards covering fructose, galactose, and alcohol metabolism based on the provided transcript.

Current fructose consumption estimate

About $35\text{--}73\text{ g/day}$, found in sucrose, high fructose corn syrup, fruits, and honey.

Fructose and protein glycation

Fructose is 8-10 times more reactive than glucose at glycating proteins.

Location of fructose metabolism

The liver is where fructose is mostly metabolized.

Fructokinase reaction

$$\text{Fructose} + \text{ATP} \rightarrow \text{Fructose-1-phosphate} + \text{ADP}$$

Aldolase B

Splits fructose-1-phosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde; also cleaves fructose-1,6-bisphosphate in glycolysis.

Glyceraldehyde kinase

Uses ATP to convert glyceraldehyde → glyceraldehyde-3-phosphate, feeding it into glycolysis.

Fructose entry point in glycolysis

Enters after the PFK-1 step, bypassing that regulatory checkpoint.

Tarui disease (Muscle PFK-1 deficiency)

Presents with easy fatigue, muscle weakness/stiffness with exercise, no rise in blood lactate during exercise, and symptoms improve after eating fructose.

Fructose benefit in PFK-1 deficiency

Fructose bypasses the defective PFK-1 step and can still enter glycolysis further downstream, giving muscle an alternate energy source.

Essential fructosuria

Benign condition from fructokinase deficiency; fructose is simply excreted since it's never phosphorylated.

Hereditary fructose intolerance (HFI)

Serious condition from aldolase B deficiency; fructose-1-phosphate accumulates and becomes toxic.

Consequences of fructose-1-phosphate buildup in HFI

Sequesters inorganic phosphate ($\text{P}_i$), blocking glycogen breakdown, gluconeogenesis, and oxidative phosphorylation.

Fructose/sorbitol IV infusion clinical lesson

A patient with unrecognized HFI given IV fructose/sorbitol developed severe hypoglycemia, liver failure, and died -- fructose infusions are dangerous in undiagnosed HFI.

Estimated daily galactose consumption

About $1\text{--}3\text{ g/day}$, found primarily in dairy products.

Galactitol

A sugar alcohol converted from galactose via aldose reductase (using NADPH).

Galactokinase

Phosphorylates galactose to galactose-1-phosphate using ATP.

Gal-1-P uridylyl transferase (GALT)

Converts galactose-1-phosphate + UDP-glucose into UDP-galactose + glucose-1-phosphate.

Epimerase (galactose metabolism)

Interconverts UDP-galactose and UDP-glucose.

Phosphoglucomutase (galactose pathway)

Converts glucose-1-phosphate to glucose-6-phosphate, feeding into glycolysis.

Galactose activation requirement

Further processing requires activated glucose in the form of a sugar-nucleotide (UDP-glucose).

UDP-galactose biosynthetic uses

Combines with glucose to form lactose, and is used to build glycoproteins and glycolipids.

Galactokinase deficiency

Causes minor problems, mainly cataracts, from galactitol accumulation.

GALT deficiency

Causes classic galactosemia -- a serious disease.

Epimerase deficiency (galactose pathway)

A rare cause of galactosemia.

Newborn screening for galactosemia

Legally mandated in every U.S. state.

Dietary galactose requirement

Some galactose intake is still needed to glycosylate proteins and lipids, even though UDP-galactose can come from UDP-glucose via epimerase.

Annual U.S. deaths from alcohol (CDC)

More than 140,000 deaths per year, including about 2,200 from acute alcohol poisoning.

Economic cost of alcohol in the U.S. (2010 estimate)

About $249 billion, or roughly $800 per person / $2.05 per drink.

Effects at BAC ~50 mg/dL

Warmth, flushing, loss of emotional restraint at $50\text{ mg/dL}$ BAC.

Effects at BAC ~100 mg/dL

Loss of fine motor skills, emotional instability at $100\text{ mg/dL}$ BAC.

Effects at BAC ~300 mg/dL

Stuporous but arousable; death possible at $300\text{ mg/dL}$ BAC.

Effects at BAC ~400-500 mg/dL

Comatose; death likely at $400\text{--}500\text{ mg/dL}$ BAC.

Alcohol absorption mechanism

Directly, with no receptors or transporters -- about 80% in the intestine, 20% in the stomach.

Food effect on alcohol absorption

Eating, especially fatty foods, slows gastric emptying and thus slows alcohol absorption.

Neurotransmitter effects of alcohol

Increases dopamine and serotonin release; enhances GABA (sedative) activity while glutamate (excitatory) stays elevated.

Step 1 of alcohol metabolism

Alcohol dehydrogenase (ADH) oxidizes ethanol to acetaldehyde, reducing $\text{NAD}^+$ to $\text{NADH}$.

Step 2 of alcohol metabolism

Aldehyde dehydrogenase 2 (ALDH2) oxidizes acetaldehyde to acetate, generating more $\text{NADH}$.

Step 3 of alcohol metabolism

Acetyl-CoA synthetase converts acetate + ATP + CoA into acetyl-CoA, AMP, and pyrophosphate.

Disulfiram (Antabuse) mechanism

Inhibits ALDH2, letting acetaldehyde accumulate and cause unpleasant symptoms after drinking.

ADH1B*2 variant

An altered ADH allele common in Asian populations that metabolizes ethanol to acetaldehyde much faster than normal.

ALDH2*2 variant

A common variant (mostly in people of Asian descent, ~560 million people) with reduced activity, causing acetaldehyde buildup, facial flushing, and increased heart rate after drinking.

MEOS (microsomal ethanol oxidizing system)

A CYP2E1-based system in the smooth ER that oxidizes ethanol using NADPH and $\text{O}_2$; induced by chronic alcohol use, can account for up to 63% of ethanol oxidation, and generates reactive oxygen species.

Chronic alcohol use and drug metabolism

Induced CYP2E1/MEOS alters metabolism of other drugs, e.g. converting acetaminophen into the toxic metabolite NAPQI.

Acetaldehyde DNA damage mechanism

Forms interstrand (and intrastrand) DNA crosslinks, contributing to its carcinogenic potential.

High NADH/NAD+ ratio effect on gluconeogenesis

Inhibits gluconeogenesis (blocks lactate$\rightarrow$pyruvate and malate$\rightarrow$oxaloacetate), which can cause lactic acidosis and hypoglycemia.

High NADH/NAD+ ratio effect on fat metabolism

Stimulates triglyceride formation and drives fatty liver disease; over 90% of AUD patients develop fatty liver.

Calories per gram of ethanol

$$7\text{ calories/gram}$$

Wernicke's encephalopathy mnemonic

CAT: Confusion, ataxia, ophthalmoplegia (treat with thiamine).

Korsakoff's psychosis mnemonic

RACK: Retrograde amnesia, anterograde amnesia, confabulation, Korsakoff's psychosis.

Cause of thiamine deficiency in alcoholics

Poor diet plus impaired thiamine absorption/utilization.

Sudden alcohol withdrawal

GABA activity falls while glutamate stays high, causing anxiety, nausea, autonomic dysfunction, and insomnia; 5-10% progress to delirium tremens, fatal in 15-20% if untreated (about 1% with benzodiazepine treatment).

Methanol metabolism danger

Metabolized by the same ADH/ALDH enzymes as ethanol, producing toxic formaldehyde/formic acid that causes eye/tissue damage and severe acidosis.

Ethylene glycol (antifreeze) metabolism

Metabolized by ADH/ALDH2 into glycoaldehyde and glycolic acid, causing severe acidosis and kidney failure.

Treatment for methanol or ethylene glycol poisoning

Saturate ADH with ethanol (the 'good' substrate) to outcompete the toxic alcohol, or give fomepizole (an ADH inhibitor).